8,784 results on '"PROGRESSIVE multifocal leukoencephalopathy"'
Search Results
2. Clinical outcomes after use of checkpoint inhibitor immunotherapies in people with multiple sclerosis.
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Nylander, Alyssa, Rowles, William, Poole, Shane, and Bove, Riley
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Retrospective studies ,immune checkpoint inhibitors ,immunotherapy ,multiple sclerosis ,neoplasms ,progressive multifocal leukoencephalopathy - Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) represent a novel class of agents approved for the treatment of several cancers and progressive multifocal leukoencephalopathy (PML). However, due to the risk of autoimmune side effects, their use in people with autoimmune diseases such as multiple sclerosis (MS) has been limited. OBJECTIVE: To characterize outcomes in a cohort of adults with MS who received ICIs. METHODS: A single-center retrospective review of medical record data was performed for people with MS treated with ICIs. RESULTS: Seven people with MS were identified, with a mean (SD) age at ICI use of 55.4 (13.7) years and a mean MS duration of 18.2 (12.2) years. Six were treated for cancer; 1 was treated for PML. After mean (SD) follow-up of 1.76 (2.15) years after ICI, outcomes are: no evidence of disease (2), residual metastatic disease (1), death due to cancer (1), death due to PML (1), and lost to follow-up (2). Notably, 0 out of 7 patients experienced an MS relapse; two out of six had new asymptomatic demyelinating magnetic resonance imaging lesions. In the three patients with expanded disability status scale (EDSS) scores at baseline and follow-up, EDSS remained stable (mean delta 0.13). CONCLUSION: In this cohort, no people with MS experienced clinical relapses and one-third experienced asymptomatic radiological activity following ICI treatment.
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- 2024
3. Tysabri Observational Cohort Study - Multiple Sclerosis (MS) Registries
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- 2024
4. Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
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- 2024
5. Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection (PENALTY)
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- 2024
6. NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
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NeoImmuneTech
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- 2024
7. Progressive multifocal leukoencephalopathy in association with siponimod treatment for secondary progressive multiple sclerosis: a case report.
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Rot, Uroš, Jerala, Miha, Horvat Ledinek, Alenka, and Brecl Jakob, Gregor
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INFORMED consent (Medical law) , *PROGRESSIVE multifocal leukoencephalopathy , *DELAYED diagnosis , *CLINICAL trials , *JOHN Cunningham virus , *LYMPHOPENIA ,CENTRAL nervous system infections - Abstract
This article, published in the Journal of Neurology, presents a case report of a middle-aged man who developed progressive multifocal leukoencephalopathy (PML) after two years of siponimod treatment for secondary progressive multiple sclerosis (SPMS). PML is a severe infection of the central nervous system caused by the John Cunningham virus (JCV), and it is most commonly associated with natalizumab therapy in MS patients. While no cases of PML associated with siponimod exposure had been published previously, three cases were reported during the clinical trial program. This case highlights the rare occurrence of PML in patients treated with siponimod and emphasizes the importance of monitoring lymphocyte counts and considering treatment discontinuation in patients with persistently low levels. [Extracted from the article]
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- 2024
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8. Pszichiátriai osztályon diagnosztizált, AIDS talaján kialakult progresszív multifokális leukoencephalopathia.
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Lovig, Csenge, Herold, Róbert, Pál, Endre, Bóné, Beáta, Faludi, Béla, Albert, Noémi, Dibusz, Dominik, Hernádi, Gabriella, Péterfi, Zoltán, Sipos, Dávid, and Tényi, Tamás
- Abstract
Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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9. Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.
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Hua-Zhen Deng, Han-Wen Zhang, Biao Huang, Jin-Huan Deng, Si-Ping Luo, Wei-Hua Li, Yi Lei, Xiao-Lei Liu, and Fan Lin
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PROGRESSIVE multifocal leukoencephalopathy ,MAGNETIZATION transfer ,ISOCITRATE dehydrogenase ,CENTRAL nervous system ,OVERALL survival ,JOHN Cunningham virus - Abstract
Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most wellestablished. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS). [ABSTRACT FROM AUTHOR]
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- 2024
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10. Frequent detection of IFN-gamma-producing memory effector and effector T cells in patients with progressive multifocal leukoencephalopathy.
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de Goër de Herve, Marie-Ghislaine, Dekeyser, Manon, Hendel-Chavez, Houria, Maillart, Elisabeth, Labeyrie, Céline, Adams, David, Moreau, Thibault, Lubetzki, Catherine, Papeix, Caroline, Stankoff, Bruno, Gasnault, Jacques, and Taoufik, Yassine
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PROGRESSIVE multifocal leukoencephalopathy ,IMMUNOLOGIC memory ,T cells ,CENTRAL nervous system ,DEMYELINATION ,JOHN Cunningham virus - Abstract
Introduction: Progressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis. Methods: Here, we developed an IFN-g release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood. Results: This assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML). Discussion: The results show this assay's frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Highly restrictive and directional penetration of the blood cerebral spinal fluid barrier by JCPyV.
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O'Hara, Bethany A., Lukacher, Avraham S., Garabian, Kaitlin, Kaiserman, Jacob, MacLure, Evan, Ishikawa, Hiroshi, Schroten, Horst, Haley, Sheila A., and Atwood, Walter J.
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CEREBROSPINAL fluid , *BLOOD-brain barrier , *CHOROID plexus , *PROGRESSIVE multifocal leukoencephalopathy , *TIGHT junctions , *CYCLOSPORINE - Abstract
The human polyomavirus JCPyV is an opportunistic pathogen that infects greater than 60% of the world's population. The virus establishes a persistent and asymptomatic infection in the urogenital system but can cause a fatal demyelinating disease in immunosuppressed or immunomodulated patients following invasion of the CNS. The mechanisms responsible for JCPyV invasion into CNS tissues are not known but direct invasion from the blood to the cerebral spinal fluid via the choroid plexus has been hypothesized. To study the potential of the choroid plexus as a site of neuroinvasion, we used an adult human choroid plexus epithelial cell line to model the blood-cerebrospinal fluid (B-CSF) barrier in a transwell system. We found that these cells formed a highly restrictive barrier to virus penetration either as free virus or as virus associated with extracellular vesicles (EVJC+). The restriction was not absolute and small amounts of virus or EVJC+ penetrated and were able to establish foci of infection in primary astrocytes. Disruption of the barrier with capsaicin did not increase virus or EVJC+ penetration leading us to hypothesize that virus and EVJC+ were highly cell-associated and crossed the barrier by an active process. An inhibitor of macropinocytosis increased virus penetration from the basolateral (blood side) to the apical side (CSF side). In contrast, inhibitors of clathrin and raft dependent transcytosis reduced virus transport from the basolateral to the apical side of the barrier. None of the drugs inhibited apical to basolateral transport suggesting directionality. Pretreatment with cyclosporin A, an inhibitor of P-gp, MRP2 and BCRP multidrug resistance transporters, restored viral penetration in cells treated with raft and clathrin dependent transcytosis inhibitors. Because choroid plexus epithelial cells are known to be susceptible to JCPyV infection both in vitro and in vivo we also examined the release of infectious virus from the barrier. We found that virus was preferentially released from the cells into the apical (CSF) chamber. These data show clearly that there are two mechanisms of penetration, direct transcytosis which is capable of seeding the CSF with small amounts of virus, and infection followed by directional release of infectious virions into the CSF compartment. Author summary: In patients with compromised immune systems due to underlying immunosuppressive diseases or due to treatment with immunomodulatory drugs, JC virus (JCPyV) invades the brain and causes a rapidly progressing and often fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). The brain is protected from invading pathogens by two major barriers, the blood-brain barrier (BBB), and the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is composed of choroid plexus epithelial cells that are directly exposed to the blood. The epithelial cells in the choroid plexus are held together by tight junctions that limit and regulate the movement of molecules and cells from the blood to the cerebral spinal fluid. In this paper we used an established adult choroid plexus epithelial cell line to model the blood-cerebrospinal fluid barrier and found that it was highly restrictive of virus penetration. The restriction was not absolute and small amounts of virus penetrated and established infection in underlying human glial cells. We also show a second mechanism of virus invasion involving direct infection of choroid plexus epithelial cells by JCPyV and directional release of infectious virions across the barrier. Both mechanisms likely contribute to the neuroinvasiveness of JCPyV. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Safety and effectiveness of disease-modifying therapies after switching from natalizumab.
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Zeineddine, Maya, Al-Roughani, Raed, Farouk Ahmed, Samar, Khoury, Samia, El-Ayoubi, Nabil, Al-Mahdawi, Akram, Al-Khabouri, Jaber, Al-Asmi, Abdullah, Chentouf, Amina, Inshasi, Jihad, Gouider, Riadh, Mrabet, Saloua, Shalaby, Nevin, Massouh, Joelle, Mohamed Ramzy Hasan Mohamed, Farah, Al-Hajje, Amal, Salameh, Pascale, Dimassi, Hani, Boumediene, Farid, and Yamout, Bassem
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PROGRESSIVE multifocal leukoencephalopathy , *MAGNETIC resonance imaging , *VIRAL antibodies , *FINGOLIMOD , *NATALIZUMAB - Abstract
Introduction: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. Objective: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. Methods: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. Results: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). Conclusion: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity. [ABSTRACT FROM AUTHOR]
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- 2024
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13. NEUROSARCOIDOSIS AS A RAPIDLY PROGRESSIVE DEMENTIA ASSOCIATED WITH NORMAL PRESSURE HYDROCEPHALUS.
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JABIF, FERNANDO, ROUSSEAU-PORTALIS, MÁXIMO, BURBANO, CLAUDIA, ANDRESIK, DIEGO, and MARTÍNEZ, BERNARDO
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Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
14. A rare case of progressive multifocal leukoencephalopathy
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Jayanthraj Gone, DO, Tyler Fontaine, DO, and Gaurav Kumar, MD
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Progressive multifocal leukoencephalopathy ,JC virus ,White matter ,HIV ,Brainstem ,Corpus callosum ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 - Abstract
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system (CNS) due to John Cunningham (JC) virus reactivation most often in immunocompromised patients. The brainstem and the anterior corpus callosum are uncommon locations for white matter lesions. We present a case of PML in a 40-year-old female presenting to the emergency department for a tonic seizure with transient postictal confusion. The inpatient workup revealed low cluster of differentiation cell counts (CD3 and CD4), transaminitis, positive drug screen, and abnormal electroencephalogram (EEG). The computed tomogram (CT) of the head and magnetic resonance image (MRI or MR) of the brain showed evidence of subcortical and periventricular white matter lesions in the right hemisphere extending into the brainstem and the left frontal lobe. The hospital course consisted of supportive measures, seizure treatment along with prophylaxis, and human immunodeficiency virus (HIV) management along with prophylactic antibiotics. The patient was discharged with appropriate medications and outpatient referrals. Overall, this case describes some key points. It highlights particular imaging characteristics of PML in the setting of inadequately treated HIV. For example, white matter lesions cross the anterior corpus callosum rather than the splenium, as in the “barbell” sign. In addition, the lesions extend inferiorly along the ipsilateral corticospinal tract into the midbrain and pons. This could be one of the first cases to capture both of these features given the rarity of their concomitant occurrence.
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- 2024
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15. Demyelinating Diseases of the CNS (Brain and Spine)
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Barkhof, Frederik, Koeller, Kelly K., Hodler, Juerg, Series Editor, Kubik-Huch, Rahel A., Series Editor, and Roos, Justus E., Series Editor
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- 2024
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16. Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells
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- 2023
17. Development of progressive multifocal leukoencephalopathy after cord blood transplantation in a patient with refractory angioimmunoblastic T-cell lymphoma.
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Aiba, Masayuki, Okada, Kohei, Funakoshi, Takumi, Nozu, Rintaro, Takahashi, Tomoki, Ozu, Shunsuke, Hidaka, Daisuke, Ogasawara, Reiki, Sugita, Junichi, Ogasawara, Masahiro, Kobayashi, Naoki, Imamura, Masahiro, Shizukawa, Hirohiko, and Ota, Shuichi
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CORD blood transplantation , *PROGRESSIVE multifocal leukoencephalopathy , *T-cell lymphoma , *MAGNETIC resonance imaging , *GRAFT versus host disease , *JOHN Cunningham virus - Abstract
A patient undergoing cord blood transplantation for refractory angioimmunoblastic T-cell lymphoma was subsequently managed with long-term immunosuppressants for chronic graft-versus-host disease (GVHD). On day 591 post-transplant, she exhibited disorientation and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain revealed two hyperintense foci in the white matter, suggestive of progressive multifocal leukoencephalopathy (PML). However, we did not include PML in the differential diagnosis at that time. Unfortunately, she developed progressive cognitive impairment, and repeated brain MRIs showed a progression in lesion size. She was still taking immunosuppressants to control her GVHD, therefore we suspected PML. The diagnosis of PML was confirmed through the detection of a John Cunningham (JC) virus in the cerebrospinal fluid on day 640 post-transplant. This report highlights the critical need to consider PML in differential diagnoses for post-allogeneic transplant patients, especially those who exhibit progressive neurological symptoms while on prolonged immunosuppressant therapy. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Progressive multifocal leukoencephalopathy in the clinical practice of a neurologist. Case report
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Yuliana A. Belova and Sergey V. Kotov
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progressive multifocal leukoencephalopathy ,natalizumab ,jc-virus ,multiple sclerosis ,inflammatory immune restoration syndrome ,Medicine (General) ,R5-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection with severe brain damage caused by the JC-virus, against the background of immunosuppressive conditions. The diagnosis of PML is complex and includes: the clinical picture, neuroimaging data, the presence of JC-virus DNA in samples of cerebrospinal fluid or brain tissue. HIV-associated PML is difficult to diagnose. In patients with multiple sclerosis, an increase in the incidence of PML is associated with the use of natalizumab. Increasing alertness towards the development and detection of PML makes it possible to achieve a favorable outcome.
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- 2024
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19. Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient
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Panos Arvanitis, Dimitrios Farmakiotis, and Ari Pelcovits
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multiple myeloma ,Progressive Multifocal Leukoencephalopathy ,teclistamab ,bispecific antibodies ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab’s potential for severe infectious complications, despite its promise in treating RRMM.
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- 2024
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20. Intracerebral haemorrhage in multiple sclerosis: assessing the impact of disease-modifying medications.
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Ou Yong, Brian M., Awuah, Wireko Andrew, Shah, Muhammad Hamza, Sanker, Vivek, Huk, Jonathan Kong Sing, Venkata, Sujashree Yadala, Patel, Diti H., Tan, Joecelyn Kirani, Khan, Noor Ayman, Kulasekaran, Ajitha, Sarkar, Manali, Abdul-Rahman, Toufik, and Atallah, Oday
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CEREBRAL hemorrhage ,MULTIPLE sclerosis ,PROGRESSIVE multifocal leukoencephalopathy ,DRUGS ,THERAPEUTICS ,AUTOIMMUNE diseases ,INTRACEREBRAL hematoma - Abstract
Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells.
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Jost, Stephanie, Ahn, Jenny, Chen, Sarah, Yoder, Taylor, Gikundiro, Kayitare Eunice, Lee, Esther, Gressens, Simon B, Kroll, Kyle, Craemer, Melissa, Kaynor, G Campbell, Lifton, Michelle, and Tan, C Sabrina
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KILLER cells , *POLYOMAVIRUS diseases , *IMMUNE recognition , *PROGRESSIVE multifocal leukoencephalopathy , *CELLULAR recognition , *IMMUNOSUPPRESSION - Abstract
Background JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections; however, NK-cell response to JCPyV infection remains unexplored. Methods NK- and T-cell responses against the JCPyV VP1 were compared using intracellular cytokine staining upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK-cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to evaluate the contribution of NK-cell receptors in immune recognition of JCPyV-infected cells. Results In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-γ production by NK cells, extending beyond T-cell responses. Next, using the NK-cell–mediated killing assay, we showed that coculture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2—a ligand for the activating NK-cell receptor NKG2D, and addition of NKG2D blocking antibodies decreased NK-cell degranulation. Conclusions NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK-cell anti-JCPyV activity. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The impact of social distancing measures on anti–JC virus serostatus changes before and during the COVID-19 pandemic in US patients with multiple sclerosis.
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Krieger, Stephen C, Sinks, Susie, Huang, Furong, Steverson, Julie, Kalina, Tamar J, White, Kurt, and Avila, Robin L
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COVID-19 pandemic , *SOCIAL distancing , *MULTIPLE sclerosis , *COVID-19 , *SEASONAL influenza - Abstract
Background: The coronavirus disease 2019 (COVID-19) pandemic offered an epidemiological opportunity to evaluate if isolation and masking affected John Cunningham (JC) virus transmission. Objective: This study aimed to assess the proportion of natalizumab-treated patients who converted to a positive anti-JCV antibody serostatus before and during the pandemic. Methods: Data from TYSABRI Outreach: Unified Commitment to Health (TOUCH) for 22,375 US patients treated with natalizumab with anti-JCV antibody records were assessed in epochs annually from 2017 to 2022. Results: Pre-pandemic anti-JCV antibody serostatus change was observed for 7.4%–7.7%. During the first and second years of the pandemic, 7.3% and 7.2% of patients' serostatus changed, respectively. Conclusion: The proportion of patients with anti-JCV antibody serostatus change did not significantly differ during the first 2 years of the pandemic compared with prior years. In contrast to seasonal influenza, masking and social distancing had no discernable effect on JCV serostatus change. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Progressive multifocal leukoencephalopathy reports in rheumatoid arthritis concerning different treatment patterns-an exploratory assessment using the food and drug administration adverse event reporting system.
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Takeshi Honma, Kenji Onda, and Koichi Masuyama
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Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening brain infection caused by the John Cunningham virus. PML is a known adverse effect associated with molecular-targeted drugs and immunosuppressive agents. Recent concerns have emerged regarding the link between methotrexate (MTX) and PML. However, limited information exists on the influence of concomitant drug use in rheumatoid arthritis (RA) treatment, where various medications are often used together. Methods: To explore treatment patterns and patient background that affect PML reporting in RA, we analyzed data on RA cases from the Food and Drug Administration Adverse Event Reporting System (FAERS; JAPIC AERS) database between 1997 and 2019. Results and Discussion: Our analysis revealed significantly elevated crude and adjusted reporting odds ratios (aROR) for MTX, rituximab (RIT), azathioprine, and cyclophosphamide. When considering treatment patterns, the concomitant use of MTX and RIT showed a higher aROR than using MTX or RIT alone. Additional TNF-a inhibitors or glucocorticoids did not increase PML reports. Moreover, male sex and older age were associated with increased PML reports. While limitations are inherent in studies using spontaneous reporting data, our exploratory assessment suggests an association between PML and the combination of MTX and RIT and a higher risk in men and older patients. These findings help enhance our understanding of PML risk factors in the context of RA treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Combined treatment with allogeneic Epstein–Barr- and human polyomavirus 1 specific T-cells in progressive multifocal leukoencephalopathy and EBV infection: a case report.
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Nay, Sandra, Möhn, Nora, Grote-Levi, Lea, Bonifacius, Agnes, Saßmann, Mieke L., Karacondi, Kevin, Tischer-Zimmermann, Sabine, Pöter, Henning, Mahmoudi, Nima, Wattjes, Mike P., Maecker-Kolhoff, Britta, Höglinger, Günter, Eiz-Vesper, Britta, and Skripuletz, Thomas
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EPSTEIN-Barr virus diseases ,POLYOMAVIRUS diseases ,T cells ,PROGRESSIVE multifocal leukoencephalopathy ,OPPORTUNISTIC infections - Abstract
Opportunistic viral infections in individuals with severe immunodeficiency can lead to fatal conditions such as progressive multifocal leukoencephalopathy (PML), for which treatment options are limited. These infections pose significant risks, especially when co-infections with other viruses occur. We describe a combined therapy approach using directly isolated allogeneic Human Polyomavirus 1 (also known as BKV) and Epstein–Barr virus (EBV) specific cytotoxic T-cells for the treatment of PML in conjunction with identified EBV in the cerebrospinal fluid (CSF) of a male patient infected with human immunodeficiency virus (HIV). A 53-year-old HIV-positive male, recently diagnosed with PML, presented with rapidly worsening symptoms, including ataxia, tetraparesis, dysarthria, and dysphagia, leading to respiratory failure. The patient developed PML even after commencing highly active antiretroviral therapy (HAART) 3 months prior. Brain magnetic resonance imaging (MRI) revealed multifocal demyelination lesions involving the posterior fossa and right thalamus suggestive of PML. In addition to the detection of human polyomavirus 2 (also known as JCV), analysis of CSF showed positive results for EBV deoxyribonucleic acid (DNA). His neurological condition markedly deteriorated over the following 2 months. Based on MRI, there was no evidence of Immune Reconstitution Inflammatory Syndrome contributing to this decline. The patient did not have endogenous virus-specific T-cells. We initiated an allogeneic, partially human leukocyte antigen-matched transfer of EBV and utilizing the cross-reactivity between BKV and JCV–BKV specific T-cells. This intervention led to notable neurological improvement and partial resolution of the MRI lesions within 6 weeks. Our case of a patient with acquired immune deficiency syndrome demonstrates that PML and concurrent EBV co-infection can still occur despite undergoing HAART treatment. This innovative experimental therapy, involving a combination of virus-specific T-cells, was demonstrated to be an effective treatment option in this patient. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Post-marketing risk analysis of bendamustine: a real-world approach based on the FAERS database.
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Dan Li, Yuan Zhang, Jia Qi Ni, Juan Zhu, Wen Ting Lu, Ya Lin Chen, Lei Cheng, Yu Qi Wang, Qian Jiang Li, Jie Wang, Yan Bing Lu, Jia Chen, and Li Chen
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DATABASES ,RISK assessment ,PROGRESSIVE multifocal leukoencephalopathy ,CHRONIC lymphocytic leukemia ,DRUG labeling - Abstract
Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia--all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time. Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Progressive multifocal leukoencephalopathy in a patient with B-cell chronic lymphocytic leukemia after COVID-19 vaccination, complicated with COVID-19 and mucormycosis: a case report.
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Amirifard, Hamed, Shahbazi, Mojtaba, Farahmand, Ghasem, Ranjbar, Zahra, Kaeedi, Maryam, and Heydari Havadaragh, Sanaz
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PROGRESSIVE multifocal leukoencephalopathy , *JOHN Cunningham virus , *CHRONIC lymphocytic leukemia , *COVID-19 vaccines , *MUCORMYCOSIS , *COVID-19 pandemic , *SYMPTOMS - Abstract
Background: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal opportunistic viral demyelinating infectious disease of the central nervous system (CNS). There are various clinical presenting symptoms for the disease. Case presentation: This paper presents a clinical case of PML in a patient with B-Chronic lymphocytic leukemia (B-CLL), previously treated with Chlorambucil, later complicated later with COVID-19 and mucormycosis. Conclusion: PML can develop in the setting of cellular immune dysfunction. Late diagnosis of this disease based on nonspecific symptoms is common, therefore when we face a neurological complication in a CLL or immunocompromised patient, we should consider PML infection. A remarkable feature of this case is the possible triggering effect of COVID-19 vaccination for emergence of PML as the disease can be asymptomatic or sub-clinical before diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Biomarkers for progressive multifocal leukoencephalopathy: emerging data for use of JC virus DNA copy number in clinical trials.
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Cortese, Irene, Norato, Gina, Harrington, Patrick R, Usher, Therri, Mainardi, Ilaria, Martin-Blondel, Guillaume, Cinque, Paola, Major, Eugene O, and Sheikh, Virginia
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PROGRESSIVE multifocal leukoencephalopathy , *JOHN Cunningham virus , *DNA viruses , *CLINICAL trials , *EXPERIMENTAL design , *BIOMARKERS - Abstract
Progressive multifocal leukoencephalopathy is a rare but devastating demyelinating disease caused by the JC virus (JCV), for which no therapeutics are approved. To make progress towards addressing this unmet medical need, innovations in clinical trial design are needed. Quantitative JCV DNA in CSF has the potential to serve as a valuable biomarker of progressive multifocal leukoencephalopathy disease and treatment response in clinical trials to expedite therapeutic development, as do neuroimaging and other fluid biomarkers such as neurofilament light chain. Specifically, JCV DNA in CSF could be used in clinical trials as an entry criterion, stratification factor, or predictor of clinical outcomes. Insights from the investigation of candidate biomarkers for progressive multifocal leukoencephalopathy might inform approaches to biomarker development for other rare diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient.
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Arvanitis, Panos, Farmakiotis, Dimitrios, and Pelcovits, Ari
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PROGRESSIVE multifocal leukoencephalopathy , *MULTIPLE myeloma , *JOHN Cunningham virus , *COVID-19 , *CEREBROSPINAL fluid , *BISPECIFIC antibodies - Abstract
This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab's potential for severe infectious complications, despite its promise in treating RRMM. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Holmes tremor in progressive multifocal leukoencephalopathy: A video case report.
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Matsushima, Takako, Ikeguchi, Ryotaro, Iijima, Mutsumi, Shimomura, Ayato, Takahashi, Shuntaro, Nakamichi, Kazuo, Shimizu, Yuko, and Kitagawa, Kazuo
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PROGRESSIVE multifocal leukoencephalopathy , *JOHN Cunningham virus , *TREMOR , *CENTRAL nervous system diseases , *DENTATE nucleus , *MAGNETIC resonance imaging - Abstract
Background: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by the John Cunningham virus. Various brain regions are affected by PML. Therefore, patients with PML show various neurological symptoms. However, tremors are rare neurological symptoms of PML. Case Presentation: A 49‐year‐old man developed intermittent slow tremor in the left hand, bilateral dysesthesia and gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the right parietofrontal lobe, right thalamus, left middle cerebellar peduncle, left dentate nucleus, pons and medulla oblongata on fluid‐attenuated inversion recovery images. The patient was positive for HIV antibodies. In addition, HIV‐1 RNA was increased. Quantitative real‐time polymerase chain reaction identified John Cunningham virus DNA in the cerebrospinal fluid; HIV‐associated PML was diagnosed. Surface electromyography showed 3‐Hz grouped discharges in the left flexor carpi ulnaris and extensor carpi radialis, which were consistent with Holmes tremor (HT). Although we administered antiretroviral therapy and mirtazapine, the neurological and radiological findings progressively worsened, and the patient died on day 90. Including the present case, there have been 10 reported cases of PML with HT. Conclusions: Although tremors are rarely observed in PML, HT might be a common tremor phenotype in patients with PML. If the neurologist observes HT in patients with multiple brain lesions, PML should be considered. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Infratentorial posterior reversible encephalopathy syndrome in INFβ1a-treated multiple sclerosis patient.
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Cutillo, Gianni, Rubin, Martina, d'Amore, Giulia, Malcangi, Massimo, Vezzulli, Paolo Q., Ferrè, Laura, Martinelli, Vittorio, Esposito, Federica, and Filippi, Massimo
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POSTERIOR leukoencephalopathy syndrome , *MULTIPLE sclerosis , *NEUROMYELITIS optica , *JOHN Cunningham virus , *THERAPEUTICS , *PROGRESSIVE multifocal leukoencephalopathy , *THROMBOTIC thrombocytopenic purpura - Abstract
This letter published in the Journal of Neurology discusses a case of posterior reversible encephalopathy syndrome (PRES) in a multiple sclerosis (MS) patient treated with interferonβ1a (INFβ1a). PRES is a clinical syndrome characterized by various symptoms and can be caused by different factors, including certain medications. The case described in the letter involved a 34-year-old woman with MS who developed PRES along with malignant hypertension. The patient's condition improved after discontinuing INF therapy and receiving antihypertensive treatment. The letter also discusses the relationship between PRES and immune-modulatory drugs used to treat MS. [Extracted from the article]
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- 2024
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31. John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis.
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Mouliou, Dimitra S.
- Abstract
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT- MS).
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Toorop, Alyssa A., van Lierop, Zoë Y. G. J., Gelissen, Liza M. Y., Hoitsma, Elske, Zeinstra, Esther M. P. E., van Rooij, Luuk C., van Munster, Caspar E. P., Vennegoor, Anke, Mostert, Jop P., Wokke, Beatrijs H. A., Kalkers, Nynke F., Hoogervorst, Erwin L. J., van Eijk, Jeroen J. J., Roosendaal, Christiaan M., Kragt, Jolijn J., Eurelings, Marijke, van Genugten, Jessie, Nielsen, Jessica, Sinnige, L. G. F., and Kloosterziel, Mark E.
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NATALIZUMAB ,DRUG monitoring ,JOHN Cunningham virus ,MULTIPLE sclerosis ,DISEASE relapse ,PROGRESSIVE multifocal leukoencephalopathy ,COVID-19 pandemic - Published
- 2024
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33. Hemorrhagic cystitis induced by JC polyomavirus infection following COVID-19: a case report.
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Lv, Yuanjie and Liu, Xiaoping
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POLYOMAVIRUS diseases ,COVID-19 pandemic ,PROGRESSIVE multifocal leukoencephalopathy ,COVID-19 ,CYSTITIS ,CORONAVIRUS diseases - Abstract
JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD). Subsequent metagenomic next-generation sequencing (mNGS) confirmed the infection to be caused by JCPyV type 2. Then, human immunoglobulin (PH4) for intravenous injection at a dose of 25 g QD was administered to the patient. Three days later, the hematuria resolved. This case illustrates that in the setting of compromised host immune function, JCPyV is not limited to causing central nervous system diseases but can also exhibit pathogenicity in the urinary system. Moreover, mNGS technology facilitates rapid diagnosis of infectious etiology by clinical practitioners, contributing to precise treatment for patients. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Spinal cord involvement in progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome.
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Moussaoui, Nisrine El, Lambert, Nicolas, Moussaoui, Majdouline El, Bianchi, Elettra, Léonard, Philippe, Moïse, Martin, and Maquet, Pierre
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PROGRESSIVE multifocal leukoencephalopathy , *IMMUNE reconstitution inflammatory syndrome , *CENTRAL nervous system diseases , *SPINAL cord , *IMMUNOSUPPRESSION , *JOHN Cunningham virus - Abstract
Progressive multifocal leukoencephalopathy (PML) is an opportunistic infectious demyelinating disease of the central nervous system caused by JC polyomavirus predominantly affecting immunocompromised individuals. Nowadays, HIV, hematological malignancies and iatrogenic immune suppression account for most PML cases. For unknown reasons, spinal cord is classically protected from PML lesions. Here, we report the course of a patient harboring spinal cord lesions in the context of PML with immune reconstitution inflammatory syndrome and review the eight other cases reported in the literature so far. Then, we discuss the evolving spectrum of PML over recent years, potentially making its diagnosis more challenging. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging.
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Yamada, Hidetada, Toko, Megumi, Nakamori, Masahiro, Ueno, Hiroki, Aoki, Shiro, Sugimoto, Tomohiro, Yasutomi, Hiroko, Nakamichi, Kazuo, and Maruyama, Hirofumi
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PROGRESSIVE multifocal leukoencephalopathy , *VITAMIN B12 deficiency , *SYSTEMIC lupus erythematosus , *MAGNETIC resonance imaging , *JOHN Cunningham virus , *NATALIZUMAB - Abstract
Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Progressive multifocal leukoencephalopathy in patients with chronic kidney disease.
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Meylor, Jennifer, Artunduaga, Daniel Crespo, Mendoza, Michael, Hooshmand, Sam I., and Obeidat, Ahmed Z.
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PROGRESSIVE multifocal leukoencephalopathy , *JOHN Cunningham virus , *CHRONIC kidney failure , *CHRONICALLY ill , *OLDER people ,CENTRAL nervous system infections - Abstract
Progressive multifocal leukoencephalopathy (PML) is an opportunistic central nervous system infection caused by the human polyomavirus 2, leading to demyelination from oligodendrocyte death and rapid neurologic decline. Most commonly, PML affects patients in immunocompromised states. However, rare reports of PML in an immunocompetent host exist. Here, we report two cases of PML in older individuals with chronic kidney disease (CKD). CKD can ultimately lead to immune system dysfunction and place patients in a relatively immunosuppressed state. Testing for JC virus should remain a consideration for rapid, unexplained neurologic decline even without known immunocompromised status in the appropriate clinical setting. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis.
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Rindi, Lorenzo Vittorio, Zaçe, Drieda, Braccialarghe, Neva, Massa, Barbara, Barchi, Virginia, Iannazzo, Roberta, Fato, Ilenia, De Maria, Francesco, Kontogiannis, Dimitra, Malagnino, Vincenzo, Sarmati, Loredana, and Iannetta, Marco
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PROGRESSIVE multifocal leukoencephalopathy , *HIGHLY active antiretroviral therapy , *RITUXIMAB , *DRUG side effects , *PROGRESSION-free survival , *HIV-positive persons , *RANDOM effects model , *HIV - Abstract
Introduction: Progressive multifocal leukoencephalopathy (PML) was first described among patients affected by hematological or solid tumors. Following the human immunodeficiency virus (HIV) epidemic, people living with HIV have represented most cases for more than a decade. With the diffusion of highly active antiretroviral therapy, this group progressively decreased in favor of patients undergoing treatment with targeted therapy/immunomodulators. In this systematic review and meta-analysis, the objective was to assess which drugs are most frequently related to PML development, and report the incidence of drug-induced PML through a meta-analytic approach. Methods: The electronic databases MEDLINE, EMBASE, ClinicalTrials.gov, Web of Science and the Canadian Agency for Drugs and Technologies in Health Database (CADTH) were searched up to May 10, 2022. Articles that reported the risk of PML development after treatment with immunomodulatory drugs, including patients of both sexes under the age of 80 years, affected by any pathology except HIV, primary immunodeficiencies or malignancies, were included in the review. The incidence of drug-induced PML was calculated based on PML cases and total number of patients observed per 100 persons and the observation time. Random-effect metanalyses were conducted for each drug reporting pooled incidence with 95% confidence intervals (CI) and median (interquartile range [IQR]) of the observation time. Heterogeneity was measured by I2 statistics. Publication bias was examined through funnel plots and Egger's test. Results: A total of 103 studies were included in the systematic review. In our analysis, we found no includible study reporting cases of PML during the course of treatment with ocrelizumab, vedolizumab, abrilumab, ontamalimab, teriflunomide, daclizumab, inebilizumab, basiliximab, tacrolimus, belimumab, infliximab, firategrast, disulone, azathioprine or danazole. Dalfampridine, glatiramer acetate, dimethyl fumarate and fingolimod show a relatively safe profile, although some cases of PML have been reported. The meta-analysis showed an incidence of PML cases among patients undergoing rituximab treatment for multiple sclerosis (MS) of 0.01 cases/100 persons (95% CI − 0.08 to 0.09; I2 = 20.4%; p = 0.25) for a median observation period of 23.5 months (IQR 22.1–42.1). Treatment of MS with natalizumab carried a PML risk of 0.33 cases/100 persons (95% CI 0.29–0.37; I2 = 50%; p = 0.003) for a median observation period of 44.1 months (IQR 28.4–60) and a mean number of doses of 36.3 (standard deviation [SD] ± 20.7). When comparing data about patients treated with standard interval dosing (SID) and extended interval dosing (EID), the latter appears to carry a smaller risk of PML, that is, 0.08 cases/100 persons (95% CI 0.0–0.15) for EID versus 0.3 cases/100 persons (95% CI 0.25–0.34) for SID. Conclusions: A higher risk of drug-related PML in patients whose immune system is not additionally depressed by means of neoplasms, HIV or concomitant medications is found in the neurological field. This risk is higher in MS treatment, and specifically during long-term natalizumab therapy. While this drug is still routinely prescribed in this field, considering the efficacy in reducing MS relapses, in other areas it could play a smaller role, and be gradually replaced by other safer and more recently approved agents. [ABSTRACT FROM AUTHOR]
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- 2024
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38. Progressive multifocal leukoencephalopathy in patients with chronic liver disease successfully treated with pembrolizumab.
- Author
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Jeantin, Lina, Shor, Natalia, Coustans, Marc, Roos-Weil, Damien, Quintin-Roué, Isabelle, Bellanger, Agnès, Le Garff-Tavernier, Magali, Ben Jemaa, Rahma, Thabut, Dominique, Pourcher, Valérie, and Weiss, Nicolas
- Subjects
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JOHN Cunningham virus , *PROGRESSIVE multifocal leukoencephalopathy , *CHRONICALLY ill , *TREATMENT effectiveness , *T-cell exhaustion , *PEMBROLIZUMAB - Abstract
This document discusses the potential use of pembrolizumab as a treatment for progressive multifocal leukoencephalopathy (PML) in patients with chronic liver disease. PML is a serious infection of the central nervous system typically observed in individuals with severe immunosuppression. The document presents two cases in which PML progression was halted with pembrolizumab treatment, resulting in improvement and regression of PML lesions. The article emphasizes the challenges faced by clinicians in diagnosing and treating PML in patients with liver disease and highlights the need for more evidence to support the use of pembrolizumab in PML treatment. [Extracted from the article]
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- 2024
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39. No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.
- Author
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Secher, Solène, Hentzien, Maxime, Cuzin, Lise, Jacomet, Christine, Hocqueloux, Laurent, Rey, David, Menard, Amélie, Arvieux, Cédric, Raffi, François, and Bani-Sadr, Firouzé
- Abstract
Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%–9.6%] vs. 5.08% [95% CI 4.8%–5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Cladribine tablets after treatment with natalizumab (CLADRINA) – rationale and design.
- Author
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Sguigna, Peter V., Hussain, Rehana Z., Okai, Annette, Blackburn, Kyle M., Tardo, Lauren, Madinawala, Mariam, Korich, Julie, Lebson, Lori A., Kaplan, Jeffrey, Salter, Amber, Manouchehri, Navid, and Stuve, Olaf
- Subjects
ANTINEOPLASTIC agents ,NATALIZUMAB ,MULTIPLE sclerosis ,DRUG efficacy ,DRUG side effects - Abstract
Background: Individual disease modifying therapies approved for multiple sclerosis (MS) have limited effectiveness and potentially serious side effects, especially when administered over long periods. Sequential combination therapy is a plausible alternative approach. Natalizumab is a monoclonal therapeutic antibody that reduces leukocyte access to the central nervous system that is associated with an increased risk of progressive multifocal leukoencephalopathy and disease reactivation after its discontinuation. Cladribine tablets act as a synthetic adenosine analog, disrupting DNA synthesis and repair, thereby reducing the number of lymphocytes. The generation of prospective, rigorous safety, and efficacy data in transitioning from natalizumab to cladribine is an unmet clinical need. Objectives: To test the feasibility of transitioning patients with relapsing forms of MS natalizumab to cladribine tablets. Design: Cladribine tablets after treatment with natalizumab (CLADRINA) is an open-label, single-arm, multicenter, collaborative phase IV, research study that will generate hypothesis regarding the safety, efficacy, and immunological impact of transition from natalizumab to cladribine tablets in patients with relapsing forms of MS. Methods and analysis: Participants will be recruited from three different sites. The primary endpoint is the absolute and percent change from baseline of lymphocytes and myeloid cell subsets, as well as blood neurofilament light levels. The secondary endpoint is the annualized relapse rate over the 12- and 24-month trial periods. Exploratory endpoints include the expanded disability status scale, and magnetic resonance imaging outcomes. Discussion: The CLADRINA trial will generate data regarding the safety, efficacy, and immunological impact of the transition from natalizumab to cladribine. As the pace of immunological knowledge of MS continues, insight into disease modifying therapy transition strategies is needed. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Frequent detection of IFN-gamma -producing memory effector and effector T cells in patients with progressive multifocal leukoencephalopathy
- Author
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Marie-Ghislaine de Goër de Herve, Manon Dekeyser, Houria Hendel-Chavez, Elisabeth Maillart, Céline Labeyrie, David Adams, Thibault Moreau, Catherine Lubetzki, Caroline Papeix, Bruno Stankoff, Jacques Gasnault, and Yassine Taoufik
- Subjects
JC virus ,progressive multifocal leukoencephalopathy ,AIDS ,multiple sclerosis ,natalizumab ,effector memory T cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionProgressive Multifocal Leukoencephalopathy (PML) is a rare and deadly demyelinating disease caused by JC virus (JCV) replication in the central nervous system. PML occurs exclusively in patients with severe underlying immune deficiencies, including AIDS and hematological malignancies. PML has also emerged as a significant threat to patients on potent new immunosuppressive biologics, including natalizumab in multiple sclerosis.MethodsHere, we developed an IFN-γ release assay (IGRA) that mainly detects JCV-specific effector memory T cells and effectors T cells in the blood.ResultsThis assay was frequently positive in patients with active PML (with a positive JCV PCR in CSF) of various underlying immunosuppression causes (84% sensitivity). Only 3% of healthy donors had a positive response (97% specificity). The frequency of positivity also increased in multiple sclerosis patients according to the time on natalizumab (up to 36% in patients treated for more than 48 months, who are considered at a higher risk of PML).DiscussionThe results show this assay’s frequent or increased positivity in patients with PML or an increased risk of PML, respectively. The assay may help to stratify the risk of PML.
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- 2024
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42. Role of Inflammation in Progressive Multifocal Leukoencephalopathy (PML)
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National Institutes of Health (NIH) and Chen Sabrina Tan, principal investigator
- Published
- 2023
43. Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy (ICIP)
- Published
- 2023
44. Progressive multifocal leukoencephalopathy in sarcoidosis successfully treated with pembrolizumab
- Author
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Öztürk, Gizem, Tekeli, Elif İrem, Erdoğan, Seyda, Peker, Elif, and Yücesan, Canan
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- 2024
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45. Progressive multifocal leukoencephalopathy and spectrum of predisposing conditions: a 20-year retrospective cohort study in a tertiary center in São Paulo, Brazil
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Mari, Julia Ferreira, de Miranda, Érique José Farias Peixoto, Mendes-Correa, Maria Cassia, Chow, Felicia C., and Vidal, José Ernesto
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- 2024
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46. Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.
- Author
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Costa-Frossard França, Lucienne, Meca Lallana, Virginia, Labiano-Fontcuberta, Andrés, Blasco, Rosario, Monreal, Enric, Martínez Ginés, María Luisa, Aguirre, Clara, Sabin Muñoz, Julia, Sainz de la Maza, Susana, Cuello, Juan Pablo, Díaz-Pérez, Carolina, Chico García, Juan Luis, Lozano Ros, Alberto, Rodríguez Jorge, Fernando, Martínez Martínez, Susana, and García Domínguez, José Manuel
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ALEMTUZUMAB , *PROGRESSIVE multifocal leukoencephalopathy , *MULTIPLE sclerosis , *MAGNETIC resonance imaging , *IDIOPATHIC thrombocytopenic purpura , *DISEASE relapse - Abstract
Background: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. Objective: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. Methods: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. Results: ARR decreased from 1.9 (95% confidence interval 1.60–2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17–0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13–0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18–0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. Conclusions: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Isolated pontocerebellar leukoencephalopathy in HIV-related PML: focus on the "shrimp sign".
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Cimmino, Angelo Tiziano, Carlomagno, Vincenzo, Sciarrone, Maria Ausilia, Di Lazzaro, Giulia, and Silvestri, Gabriella
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JOHN Cunningham virus , *LEUKOENCEPHALOPATHIES , *SHRIMPS , *SCIENTIFIC literature , *PROGRESSIVE multifocal leukoencephalopathy , *NEUROLOGIC examination , *CENTRAL nervous system diseases - Abstract
This article describes a case study of a 67-year-old man who presented with speech and gait disturbances following an episode of gastroenteritis. The patient had cerebellar dysarthria and limb incoordination, and an MRI revealed bilateral lesions in the white matter of the brain. Further testing confirmed a diagnosis of progressive multifocal leukoencephalopathy (PML) caused by reactivation of the John Cunningham virus (JCV) in the context of HIV infection. The article discusses the typical features of PML on MRI and highlights the importance of early recognition and treatment. [Extracted from the article]
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- 2024
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48. Progressive multifocal leukoencephalopathy in a lung transplant recipient.
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Sakizadeh, Jason, Davis, Michael J., and Fontana, Lauren
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PROGRESSIVE multifocal leukoencephalopathy , *JOHN Cunningham virus , *LUNG transplantation , *CENTRAL nervous system diseases , *DEMYELINATION - Abstract
Key Clinical Message: Progressive multifocal leukoencephalopathy (PML) is a rare and fatal demyelinating disease of the central nervous system (CNS). The case we describe highlights the importance of considering a diagnosis of PML early (<1 year) after lung transplant. [ABSTRACT FROM AUTHOR]
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- 2024
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49. 系统性红斑狼疮患者应用靶向 B 细胞治疗后发生中枢神经 系统病变文献病例分析.
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姜莉, 贾倩, 厉彦山, 王莉莉, 李红, and 李尊忠
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Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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50. A pharmacovigilance study on antibody-drug conjugate (ADC)-related neurotoxicity based on the FDA adverse event reporting system (FAERS).
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Linlin Tang, Cuicui Sun, Wenshan Liu, Haiyan Wu, and Chuanhua Ding
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ANTIBODY-drug conjugates ,PROGRESSIVE multifocal leukoencephalopathy ,CELL surface antigens ,NEUROTOXICOLOGY ,CEREBRAL hemorrhage - Abstract
Background: Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents that use monoclonal antibodies to specifically recognize tumour cell surface antigens. However, off-target effects may lead to severe adverse events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse Event Reporting System (FAERS) database. Research design and methods: Data were extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the clinical characteristics of ADC-related neurological adverse events (AEs). We used the reporting odds ratio (ROR) and proportional reporting ratio (PRR) for the disproportionality analysis to evaluate the potential association between AEs and ADCs. Results: A total of 562 cases of neurological AEs were attributed to ADCs. The median age was 65 years old [(Min; Max) = 3; 92]. Neurotoxic signals were detected in patients receiving brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan. The payloads of brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and trastuzumab emtansine were microtubule polymerization inhibitors, which are more likely to develop neurotoxicity. We also found that brentuximab vedotinand gemtuzumab ozogamicin-related neurological AEs were more likely to result in serious outcomes. The eight most common ADC-related nervous system AE signals were peripheral neuropathy [ROR (95% CI) = 16.98 (14.94-19.30), PRR (95% CI) = 16.0 (14.21-18.09)], cerebral haemorrhage [ROR (95% CI) = 9.45 (7.01-12.73), PRR (95% CI) = 9.32 (6.95-12.50)], peripheral sensory neuropathy [ROR (95% CI) = 47.87 (33.13-69.19), PRR (95% CI) = 47.43 (32.93-68.30)], polyneuropathy [ROR (95% CI) = 26.01 (18.61-36.33), PRR (95% CI) = 25.75 (18.50-35.86)], encephalopathy [ROR (95% CI) = 5.16 (3.32-8.01), PRR (95% CI) = 5.14 (3.32-7.96)], progressive multifocal leukoencephalopathy [ROR (95% CI) = 22.67 (14.05-36.58), PRR (95% CI) = 22.52 (14.01-36.21)], taste disorder [ROR (95% CI) = 26.09 (15.92-42.76), PRR (95% CI) = 25.78 (15.83-42.00)], and guillain barrier syndrome [ROR (95% CI) = 17.844 (10.11-31.51), PRR (95% CI) = 17.79 (10.09-31.35)]. The mortality rate appeared to be relatively high concomitantly with AEs in the central nervous system. Conclusion: ADCs may increase the risk of neurotoxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADC drugs, combining the FAERS data with other data sources is crucial for monitoring the neurotoxicity of ADCs. Further studies on the potential mechanisms and preventive measures for ADC-related neurotoxicity are necessary. [ABSTRACT FROM AUTHOR]
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- 2024
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