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1

Dalsgaard Hansen, N. J., C. Madsen, and E. Stenager. "Progressive multifocal leucoencephalopathy." Italian Journal of Neurological Sciences 17, no. 6 (December 1996): 393–99. http://dx.doi.org/10.1007/bf01997713.

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2

Kleiter, Ingo, Michael Schröder, Ralf Lürding, Gerhard Schuierer, David B. Clifford, Ulrich Bogdahn, Andreas Steinbrecher, and Peter Pöschl. "Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy." Multiple Sclerosis Journal 16, no. 6 (May 7, 2010): 749–53. http://dx.doi.org/10.1177/1352458510367718.

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Progressive multifocal leucoencephalopathy has become a growing concern in natalizumab-treated multiple sclerosis patients. Here, we describe a 35-year-old patient who was treated with 34 infusions of natalizumab before complaining about visual deterioration. MRI was non-diagnostic and JC virus testing initially was negative. Electroencephalography showed severe slowing of the right hemisphere, and neuropsychological testing revealed right frontal and temporal deficits. The diagnosis of progressive multifocal leucoencephalopathy was established 2 months later by typical MRI presentation and detection of JC virus DNA in the cerebrospinal fluid. Functional neurological deficits may precede imaging features and should prompt early consideration of progressive multifocal leucoencephalopathy.
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3

Berger, J. R. "Natalizumab and progressive multifocal leucoencephalopathy." Annals of the Rheumatic Diseases 65, suppl_3 (November 1, 2006): iii48—iii53. http://dx.doi.org/10.1136/ard.2006.058404.

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4

&NA;. "Zidovudine battles progressive multifocal leucoencephalopathy." Inpharma Weekly &NA;, no. 750 (August 1990): 10. http://dx.doi.org/10.2165/00128413-199007500-00023.

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5

Lafeuillade, A., C. Poggi, C. Tamalet, P. Pellegrino, N. Profizi, R. Quilichini, and C. Sayada. "Progressive multifocal leucoencephalopathy in AIDS." AIDS 9, no. 7 (July 1995): 819–20. http://dx.doi.org/10.1097/00002030-199507000-00027.

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6

Molloy, O. E., C. C. Foley, A. Lally, B. Moriarty, P. Collins, J. O'Gorman, C. F. de Gascun, and B. Kirby. "Progressive multifocal leucoencephalopathy and psoriasis." British Journal of Dermatology 177, no. 1 (June 5, 2017): 271–72. http://dx.doi.org/10.1111/bjd.15028.

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7

Maxwell, Alice, Hilary Archer, Nicki Cohen, Seth Love, and David Cottrell. "PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY: AN ATYPICAL CASE." Journal of Neurology, Neurosurgery & Psychiatry 86, no. 11 (October 14, 2015): e4.185-e4. http://dx.doi.org/10.1136/jnnp-2015-312379.90.

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Case reportA 71 year old man presented with a three month history of gradual arm and leg weakness, followed by neck stiffness, dysphagia, dysarthria and hypophonia. Past Medical History included Burkitt's lymphoma of the jaw 14 years previously, treated with chemotherapy and radiotherapy.Examination demonstrated a restriction of upgaze and dysphonia. Tone was markedly increased, and power reduced globally at a grading of 4/5. Reflexes were brisk with an upgoing left plantar.Investigations revealed, longstanding idiopathic lymphopenia for 10 years, CT chest/abdominal/pelvis was normal, serial MRI of the brain demonstrated changes in the subcortical white matter, frontal and parietal lobes. JC virus PCR was negative, however, brain biopsy was consistent with Progressive Multifocal Leucoencephalopathy (PML).DiscussionPML is caused by reactivation of the polyomavirus JC in the CNS. Reactivation typically occurs following immunosuppression e.g. HIV, haematological malignancies and drugs. Gold standard for diagnosis is brain biopsy as JC virus PCR has a sensitivity of only 80%. Treatment is through removal of the immunosuppressive agent, and immune reconstitution.PML should be considered in all patients with a suggestive clinical and radiological presentation where there is current or historical immunosuppression, should JC virus PCR be negative a tissue biopsy should be sought.
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8

Gilotra, Tarvinder S., and Ambika P. Eranki. "1766. Osimertinib-Associated Progressive Multifocal Leucoencephalopathy." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S650—S651. http://dx.doi.org/10.1093/ofid/ofz360.1629.

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Abstract Background Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of white matter in the central nervous system (CNS) caused by reactivation of John Cunningham (JC) virus. Drug-induced PML is increasingly reported with the widely used biological immunosuppressant drugs and molecular targeted antineoplastic agents. Monoclonal antibodies were the pioneer drugs to be associated with PML including the prototypical natalizumab. Methods Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been rarely described in this context with few case reports of ibrutinib-associated PML. Osimertinib, a third-generation EGFR TKI, was recently FDA-approved for the first-line treatment of metastatic non-small-cell lung cancer (NSCLC), and to the best of our knowledge has never been associated with PML. We describe a case report of a rapidly progressive PML likely associated with osimertinib therapy. Results A 85-year-old female with history of NSCLC, on osimertinib, was admitted with progressively worsening left hemiparesis, facial palsy, unsteady gait, recurrent falls, and episodic confusion over a period of month. Brain magnetic resonance imaging revealed foci of non-enhancing increased T2 and fluid-attenuated inversion recovery (FLAIR) signal intensity in the periventricular and bilateral cerebral subcortical white matter. MRI cervical spine was unremarkable for acute enhancing lesions. Cerebrospinal fluid (CSF) was unremarkable for infectious etiology, oligoclonal bands, and cytology. The patient was readmitted 2 weeks later with worsening neurological deficits and new lesions in the bilateral middle cerebellar peduncles, pons, midbrain, and cerebral white matter. Positive CSF JC virus PCR lead to the final diagnosis of “probable” PML. Biopsy was deferred for high clinical suspicion of PML and procedural risks outweighing benefits. Osimertinib was likely contributing to PML in the absence of other immunosuppression. Conclusion Inhibition of tyrosine kinase-dependent pathways can potentially aid in the replication of JC virus per previously reported ibrutinib-associated PML. Clinicians should be aware of PML risk in patients on osimertinib and TKI therapy, especially those with positive serum JC virus serology. Disclosures All authors: No reported disclosures.
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9

Bowler, J. V., P. T. G. Davies, and G. D. Perkin. "99TcmHMPAO SPECT in progressive multifocal leucoencephalopathy." British Journal of Radiology 65, no. 773 (May 1992): 447–49. http://dx.doi.org/10.1259/0007-1285-65-773-447.

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10

Bjerrum, Ole Weis, and Ole Evald Hansen. "Progressive multifocal leucoencephalopathy in Hodgkin's disease." Scandinavian Journal of Haematology 34, no. 5 (April 24, 2009): 442–45. http://dx.doi.org/10.1111/j.1600-0609.1985.tb00775.x.

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11

Keith, J., F. Pirouzmand, P. Diamandis, and Z. Ghorab. "Intraoperative cytodiagnosis of progressive multifocal leucoencephalopathy." Cytopathology 25, no. 1 (February 15, 2013): 59–61. http://dx.doi.org/10.1111/cyt.12047.

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12

O’Riordan, S., C. McGuigan, M. Farrell, and M. Hutchinson. "Progressive multifocal leucoencephalopathy presenting with Parkinsonism." Journal of Neurology 250, no. 11 (November 2003): 1379–81. http://dx.doi.org/10.1007/s00415-003-0194-1.

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13

O'Reilly, Seamus. "Efficacy of camptothecin in progressive multifocal leucoencephalopathy." Lancet 350, no. 9073 (July 1997): 291. http://dx.doi.org/10.1016/s0140-6736(05)62256-8.

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14

Vollmer-Haase, J., P. Young, and EB Ringelstein. "Efficacy of camptothecin in progressive multifocal leucoencephalopathy." Lancet 350, no. 9073 (July 1997): 291. http://dx.doi.org/10.1016/s0140-6736(05)62257-x.

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15

Vollmer-Haase, Juliane, Peter Young, and E. Bernd Ringelstein. "Efficacy of camptothecin in progressive multifocal leucoencephalopathy." Lancet 349, no. 9062 (May 1997): 1366. http://dx.doi.org/10.1016/s0140-6736(05)63201-1.

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16

WILLIAMSON, P. J., N. C. ALLAN, and M. A. McINTYRE. "Cerebral Hodgkin's disease and progressive multifocal leucoencephalopathy." Clinical & Laboratory Haematology 11, no. 3 (September 1989): 281–85. http://dx.doi.org/10.1111/j.1365-2257.1989.tb00221.x.

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17

Knight, R. S. G., N. M. Hyman, S. D. Gardner, P. E. Gibson, M. M. Esiri, and C. P. Warlow. "Progressive multifocal leucoencephalopathy and viral antibody titres." Journal of Neurology 235, no. 8 (November 1988): 458–61. http://dx.doi.org/10.1007/bf00314247.

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18

Itoh, Christopher Yuki, Han Sung Lee, and Alan Howe Yee. "Grey matter abnormality in progressive multifocal leucoencephalopathy." Practical Neurology 21, no. 3 (March 30, 2021): 225–27. http://dx.doi.org/10.1136/practneurol-2020-002852.

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Progressive multifocal leucoencephalopathy (PML) is a demyelinating white matter disease that most often affects immunocompromised people infected by JC virus. The diagnostic gold standard is demonstrable viral DNA or protein from histopathological tissue. However, there are few detailed descriptions of cortical grey matter involvement on neuroimaging. Here we describe the histopathological correlate of cerebral grey matter involvement and radiological accompaniment in a patient with biopsy proven PML.
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19

Danovska, M., E. Ovcharova, D. Marinova-Trifonova, and I. Mladenovski. "Chlorambucil- Induced progressive multifocal leucoencephalopathy - A case report." Journal of the Neurological Sciences 405 (October 2019): 166. http://dx.doi.org/10.1016/j.jns.2019.10.1095.

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20

Patil, M. A., N. N. Redkar, R. Balikar, and J. Shah. "Progressive multifocal leucoencephalopathy isolated to the posterior fossa." Case Reports 2013, jan30 1 (January 30, 2013): bcr2012008078. http://dx.doi.org/10.1136/bcr-2012-008078.

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21

Boerman, R. H., E. P. Arnoldus, A. K. Raap, A. C. Peters, J. ter Schegget, and M. van der Ploeg. "Diagnosis of progressive multifocal leucoencephalopathy by hybridisation techniques." Journal of Clinical Pathology 42, no. 2 (February 1, 1989): 153–61. http://dx.doi.org/10.1136/jcp.42.2.153.

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22

Domingo, Pere, Josep Maria Guardiola, Alex Iranzo, and Nuria Margall. "Remission of progressive multifocal leucoencephalopathy after antiretroviral therapy." Lancet 349, no. 9064 (May 1997): 1554–55. http://dx.doi.org/10.1016/s0140-6736(05)62136-8.

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23

Baldeweg, Torsten, and José Catalan. "Remission of progressive multifocal leucoencephalopathy after antiretroviral therapy." Lancet 349, no. 9064 (May 1997): 1555. http://dx.doi.org/10.1016/s0140-6736(05)62137-x.

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24

McNALLY, PAUL G., JULIA M. TAYLOR, and J. K. WOOD. "Progressive multifocal leucoencephalopathy associated with chronic lymphocytic leukaemia." Clinical & Laboratory Haematology 10, no. 2 (June 1988): 229–33. http://dx.doi.org/10.1111/j.1365-2257.1988.tb01177.x.

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25

MANJI, H. "Progressive multifocal leucoencephalopathy: progress in the AIDS era." Journal of Neurology, Neurosurgery & Psychiatry 69, no. 5 (November 1, 2000): 569–71. http://dx.doi.org/10.1136/jnnp.69.5.569.

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26

Le Roux-Villet, C., L. Michel, J. Gasnault, Y. Taoufik, and H. Bachelez. "Progressive multifocal leucoencephalopathy in a patient with Sézary syndrome." British Journal of Dermatology 163, no. 5 (June 9, 2010): 1118–20. http://dx.doi.org/10.1111/j.1365-2133.2010.09896.x.

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27

Flanagan, Peter, and Christine Costello. "Progressive multifocal leucoencephalopathy in patients with chronic lymphocytic leukaemia." Clinical & Laboratory Haematology 11, no. 1 (March 1989): 78–79. http://dx.doi.org/10.1111/j.1365-2257.1989.tb00183.x.

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28

Shprecher, D., T. Frech, S. Chin, R. Eskandari, and J. Steffens. "Progressive multifocal leucoencephalopathy associated with lupus and methotrexate overdose." Lupus 17, no. 11 (November 2008): 1029–32. http://dx.doi.org/10.1177/0961203308089435.

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29

LØKEN, AAGOT CHRISTIE, SIGVALD REFSUM, and WILLIAM JACOBSEN. "PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY IN A CASE OF BOECK'S SARCOIDOSIS." Acta Neurologica Scandinavica 39, S4 (January 29, 2009): 301. http://dx.doi.org/10.1111/j.1600-0404.1963.tb01847.x.

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30

Sobha, N. "Progressive multifocal leucoencephalopathy with discrete involvement of pyramidal tract." Journal of Neurology, Neurosurgery & Psychiatry 76, no. 1 (January 1, 2005): 24. http://dx.doi.org/10.1136/jnnp.2004.046003.

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31

Aure, K. "Dramatic improvement in non-AIDS related progressive multifocal leucoencephalopathy." Journal of Neurology, Neurosurgery & Psychiatry 76, no. 9 (September 1, 2005): 1305–6. http://dx.doi.org/10.1136/jnnp.2004.061408.

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32

Williams-Gray, C. H., S. H. Aliyu, A. M. L. Lever, A. F. Dean, and G. G. Lennox. "Reversible parkinsonism in a patient with progressive multifocal leucoencephalopathy." Journal of Neurology, Neurosurgery & Psychiatry 78, no. 4 (October 3, 2006): 408–10. http://dx.doi.org/10.1136/jnnp.2006.103259.

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33

Scarpazza, Cristina, Alessio Signori, Luca Prosperini, Maria Pia Sormani, Mirco Cosottini, Ruggero Capra, and Simonetta Gerevini. "Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution." Journal of Neurology, Neurosurgery & Psychiatry 90, no. 3 (November 2, 2018): 261–67. http://dx.doi.org/10.1136/jnnp-2018-319208.

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ObjectiveEarly diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter.MethodsAll Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant.Results(1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort.ConclusionsConsidering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3–4 months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.
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34

Nicoli, F., B. Chave, J. C. Peragut, and J. L. Gastaut. "Efficacy of cytarabine in progressive multifocal leucoencephalopathy in AIDS." Lancet 339, no. 8788 (February 1992): 306. http://dx.doi.org/10.1016/0140-6736(92)91376-j.

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35

de Truchis, Pierre, Marie Flament-Saillour, Jon-Andoni Urtizberea, Daniel Hassine, and Bernard Clair. "Inefficacy of cytarabine in progressive multifocal leucoencephalopathy in AIDS." Lancet 342, no. 8871 (September 1993): 622–23. http://dx.doi.org/10.1016/0140-6736(93)91453-s.

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36

Portegies, Peter, PaulR Algra, CarlaE M. Hollak, JanM Prins, Peter Reiss, Jaap Valk, and JoepM A. Lange. "Response to cytarabine in progressive multifocal leucoencephalopathy in AIDS." Lancet 337, no. 8742 (March 1991): 680–81. http://dx.doi.org/10.1016/0140-6736(91)92504-u.

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37

Abdulqawi, R., K. Ashawesh, P. Newman, and P. O'Neil. "Progressive multifocal leucoencephalopathy in a case of chronic lymphocytic leukaemia." Journal of Clinical Virology 36 (January 2006): S44. http://dx.doi.org/10.1016/s1386-6532(06)80867-x.

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38

Boulton-Jones, J. R., C. Fraser-Moodie, and S. D. Ryder. "Long term survival from progressive multifocal leucoencephalopathy after liver transplantation." Journal of Hepatology 35, no. 6 (December 2001): 828–29. http://dx.doi.org/10.1016/s0168-8278(01)00202-1.

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39

Kaye, B. R., C. M. Neuwelt, S. S. London, and S. J. DeArmond. "Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy." Annals of the Rheumatic Diseases 51, no. 10 (October 1, 1992): 1152–56. http://dx.doi.org/10.1136/ard.51.10.1152.

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40

Hoffmann, C. "Progressive multifocal leucoencephalopathy with unusual inflammatory response during antiretroviral treatment." Journal of Neurology, Neurosurgery & Psychiatry 74, no. 8 (August 1, 2003): 1142–44. http://dx.doi.org/10.1136/jnnp.74.8.1142.

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41

Hasan, Muhammad Mehedi, and Peter Taylor. "Progressive multifocal leucoencephalopathy in a case of chronic lymphocytic leukaemia." British Journal of Haematology 130, no. 6 (September 2005): 808. http://dx.doi.org/10.1111/j.1365-2141.2005.05587.x.

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42

Louarn, F., F. Gray, A. Gaston, R. Gherardi, C. Keohane, and J. D. Degos. "Extensive form of progressive multifocal leucoencephalopathy associated with laryngeal carcinoma." Journal of Neurology 234, no. 2 (February 1987): 107–11. http://dx.doi.org/10.1007/bf00314113.

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43

Ray, Manoj, Jeffrey R. Curtis, and John W. Baddley. "A case report of progressive multifocal leucoencephalopathy (PML) associated with adalimumab." Annals of the Rheumatic Diseases 73, no. 7 (March 11, 2014): 1429–30. http://dx.doi.org/10.1136/annrheumdis-2013-204978.

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44

Travasarou, M., E. Giannouli, T. Kalamatas, S. Marousi, A. Ladas, C. Zografou, E. Vrentzou, C. Samara, and C. Karageorgiou. "Natalizumab-Associated Progressive Multifocal Leucoencephalopathy: Lessons from Four Different Cases (P07.053)." Neurology 78, Meeting Abstracts 1 (April 22, 2012): P07.053. http://dx.doi.org/10.1212/wnl.78.1_meetingabstracts.p07.053.

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45

Ripellino, P., C. Comi, M. Mula, C. Varrasi, A. Conconi, A. Stecco, D. Brustia, et al. "Progressive multifocal leucoencephalopathy after autologous bone marrow transplantation: a treatment option." Case Reports 2011, apr15 1 (April 15, 2011): bcr1120103549. http://dx.doi.org/10.1136/bcr.11.2010.3549.

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46

Vulliemoz, S. "Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis." Journal of Neurology, Neurosurgery & Psychiatry 77, no. 9 (May 18, 2006): 1079–82. http://dx.doi.org/10.1136/jnnp.2006.092353.

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47

Chang, AAPT, S. Jayasinghe, S. Rajapakse, and MHR Sheriff. "A patient presenting with features of progressive multifocal leucoencephalopathy in HIV/AIDS." Ceylon Medical Journal 46, no. 4 (January 27, 2014): 153. http://dx.doi.org/10.4038/cmj.v46i4.6468.

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48

Berger, Joseph. "Case definitions for progressive multifocal leucoencephalopathy: a step in the right direction." Journal of Neurology, Neurosurgery & Psychiatry 83, no. 9 (July 17, 2012): 856–57. http://dx.doi.org/10.1136/jnnp-2012-303260.

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49

Svensson, Per-Åke, and Elna-Marie Larsson. "Infratentorial progressive multifocal leucoencephalopathy (PML) in a patient with SLE (2008: 4b)." European Radiology 18, no. 7 (June 17, 2008): 1526–28. http://dx.doi.org/10.1007/s00330-007-0788-6.

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50

Sawan, Nitish J., and Anita Basavaraj. "Progressive multifocal leucoencephalopathy as a manifestation of immune reconstitution inflammatory syndrome in a patient with HIV infection: a case report." International Journal of Advances in Medicine 7, no. 7 (June 22, 2020): 1187. http://dx.doi.org/10.18203/2349-3933.ijam20202597.

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Immune reconstitution inflammatory syndrome (IRIS) is defined as paradoxical worsening of a known condition or the appearance of a new condition after initiating antiretroviral therapy (ART) in HIV-infected patients. IRIS results from restored immunity to specific infectious or non-infectious antigens. Immune reconstitution following initiation of ART may lead to activation of an inflammatory response to detectable or latent JC virus (JCV) infection, an etiological agent of progressive multifocal leucoencephalopathy (PML). We present an interesting case of IRIS manifesting as PML in a newlydiagnosed HIV-infected patient started on ART.
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