{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:52:44Z","timestamp":1782823964382,"version":"3.54.5"},"reference-count":10,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This is a case report concerning a Natalizumab-associated Progressive Multifocal Leukoencephalopathy (PML) with cerebellar localization and wakefulness disturbances. Awakening and clinical improvement dramatically occurred as soon as the immune reconstitution inflammatory syndrome (IRIS) took place, being it mild in nature and colocalizing with the PML lesion. In these ideal experimental conditions, we applied brain magnetic resonance imaging post-analysis in order to know changes in brain volumes underlying the pathological process over the infection period. White matter volume increased with a decrease in grey matter during IRIS. Conversely, we found a constant increase in cerebrospinal fluid volume throughout the duration of PML, suggesting a widespread abiotrophic effect, far from the lesion. Furthermore, brain parenchymal fraction significantly decreased as expected while the total brain volume remained stable at all times. Neurodegeneration is the main contributor to the steady disability in Natalizumab-associated PML. This process is thought to be widespread and inflammatory in nature as well as sustained by IRIS and humoral factors derived from the PML lesion.<\/jats:p>","DOI":"10.3390\/ijms232113642","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T10:53:06Z","timestamp":1667904786000},"page":"13642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Changes in Brain Volumes Are Relevant during Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: Lessons from a Case Report"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-8112","authenticated-orcid":false,"given":"Roberto","family":"De Masi","sequence":"first","affiliation":[{"name":"Complex Operative Unit of Neurology, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Italy"},{"name":"Laboratory of Neuroproteomics, Multiple Sclerosis Centre, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-9228","authenticated-orcid":false,"given":"Stefania","family":"Orlando","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroproteomics, Multiple Sclerosis Centre, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Armenise","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Radiology, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantaleo","family":"Spagnolo","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Radiology, \u201cF. Ferrari\u201d Hospital, 73042 Casarano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-3406","authenticated-orcid":false,"given":"Ruggero","family":"Capra","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Spedali Civili di Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmela","family":"Costa","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Ophthalmology, \u201cV. Fazzi\u201d Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S1474-4422(10)70040-5","article-title":"Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: Clinical features and pathogenesis","volume":"9","author":"Tan","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S1474-4422(18)30040-1","article-title":"Pathogenesis of progressive multifocal leukoencephalopathy and risks associated with treatments for multiple sclerosis: A decade of lessons learned","volume":"17","author":"Major","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.msard.2017.01.006","article-title":"Classifying PML risk with diseasemodifying therapies","volume":"12","author":"Berger","year":"2017","journal-title":"Mult. 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