PMC:4925684 / 8841-11749 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/4925684","sourcedb":"PMC","sourceid":"4925684","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4925684","text":"Discussion\nThese cases demonstrate three novel important points. First, PML may recur years after the initial illness, despite normal or near-normal immune function. Second, recurrence of clinical PML may be presaged by MRI brain changes. Third, the MRI changes may fluctuate over time.\nWe believe JCV caused the clinical, radiological, and neuropathological features described. In both cases, clinical and MRI findings were compatible with PML (Brew et al. 2010; Gheuens et al. 2013), although in the first case, the fluctuating cortical gyriform enhancement is unusual. The pathology was also consistent with PML except the microvascular proliferation. Hyperperfusion within and at the edge of PML lesions has previously been demonstrated, however it was unclear whether this was due to microvascular proliferation or vasodilation (Khoury et al. 2013).\nSV40 staining was seen in cortical neurons in the first case. This has been described in up to half of patients with classic PML, within areas of cortical demyelination or in isolation (Wuthrich and Koralnik 2012). Our patient’s biopsy showed cortical demyelination with infection of astrocytes and neurons and some inflammation. This is consistent with cortical involvement by PML, which may explain the cortical gyriform enhancement seen on MRI.\nMost importantly, JCV DNA was detected in the CSF and brain of both patients by several techniques. No alternative cause was found. Autopsies of HIV infected patients have previously shown “burnt out” cerebral lesions from long term PML without evidence of JCV activity (Gray et al. 2003). There is no clear reason why these two patients in particular had PML recurrence; hypotheses include an undetermined host genetic predisposition, HIV-accelerated age related immune senescence, or viral factors such as development of a mutation in a JCV quasi-species.\nJCV DNA has previously been found in low copy number in CSF up to one half of natalizumab associated PML patients months (and in one case three years) after PML stabilization off natalizumab (Ryschkewitsch et al. 2010). However those patients had no definite evidence of clinically active disease in contradistinction to our two patients.\nThese cases therefore have significant implications for the prognosis and management of patients with JCV CNS infection. Although PML often improves with HAART, our findings suggest this population, and others with PML, may be at risk of PML recurrence. Serial monitoring clinically and by MRI may allow early identification. There is no proven PML therapy besides immune reconstitution (Tan et al. 2009; Koralnik 2006), which is of particular concern given that our patients were not immunosuppressed anymore. However, should PML recurrence be identified in other groups such as natalizumab or fumarates-treated patients, current immunomodulating and immunosuppressive therapies may need to be reconsidered.","divisions":[{"label":"title","span":{"begin":0,"end":10}},{"label":"p","span":{"begin":11,"end":286}},{"label":"p","span":{"begin":287,"end":854}},{"label":"p","span":{"begin":855,"end":1302}},{"label":"p","span":{"begin":1303,"end":1860}},{"label":"p","span":{"begin":1861,"end":2199}}],"tracks":[{"project":"2_test","denotations":[{"id":"26727910-24088807-63343916","span":{"begin":848,"end":852},"obj":"24088807"},{"id":"26727910-24088807-63343916","span":{"begin":848,"end":852},"obj":"24088807"},{"id":"26727910-22157619-63343917","span":{"begin":1063,"end":1067},"obj":"22157619"},{"id":"26727910-22157619-63343917","span":{"begin":1063,"end":1067},"obj":"22157619"},{"id":"26727910-12769183-63343918","span":{"begin":1586,"end":1590},"obj":"12769183"},{"id":"26727910-12769183-63343918","span":{"begin":1586,"end":1590},"obj":"12769183"},{"id":"26727910-20818792-63343919","span":{"begin":2074,"end":2078},"obj":"20818792"},{"id":"26727910-20818792-63343919","span":{"begin":2074,"end":2078},"obj":"20818792"},{"id":"26727910-19129505-63343920","span":{"begin":2599,"end":2603},"obj":"19129505"},{"id":"26727910-19129505-63343920","span":{"begin":2599,"end":2603},"obj":"19129505"},{"id":"26727910-16862584-63343921","span":{"begin":2614,"end":2618},"obj":"16862584"},{"id":"26727910-16862584-63343921","span":{"begin":2614,"end":2618},"obj":"16862584"},{"id":"T80876","span":{"begin":848,"end":852},"obj":"24088807"},{"id":"T41320","span":{"begin":848,"end":852},"obj":"24088807"},{"id":"T76033","span":{"begin":1063,"end":1067},"obj":"22157619"},{"id":"T26738","span":{"begin":1063,"end":1067},"obj":"22157619"},{"id":"T42402","span":{"begin":1586,"end":1590},"obj":"12769183"},{"id":"T44250","span":{"begin":1586,"end":1590},"obj":"12769183"},{"id":"T34124","span":{"begin":2074,"end":2078},"obj":"20818792"},{"id":"T33244","span":{"begin":2074,"end":2078},"obj":"20818792"},{"id":"T71233","span":{"begin":2599,"end":2603},"obj":"19129505"},{"id":"T16373","span":{"begin":2599,"end":2603},"obj":"19129505"},{"id":"T82064","span":{"begin":2614,"end":2618},"obj":"16862584"},{"id":"T2854","span":{"begin":2614,"end":2618},"obj":"16862584"}],"attributes":[{"subj":"26727910-24088807-63343916","pred":"source","obj":"2_test"},{"subj":"26727910-24088807-63343916","pred":"source","obj":"2_test"},{"subj":"26727910-22157619-63343917","pred":"source","obj":"2_test"},{"subj":"26727910-22157619-63343917","pred":"source","obj":"2_test"},{"subj":"26727910-12769183-63343918","pred":"source","obj":"2_test"},{"subj":"26727910-12769183-63343918","pred":"source","obj":"2_test"},{"subj":"26727910-20818792-63343919","pred":"source","obj":"2_test"},{"subj":"26727910-20818792-63343919","pred":"source","obj":"2_test"},{"subj":"26727910-19129505-63343920","pred":"source","obj":"2_test"},{"subj":"26727910-19129505-63343920","pred":"source","obj":"2_test"},{"subj":"26727910-16862584-63343921","pred":"source","obj":"2_test"},{"subj":"26727910-16862584-63343921","pred":"source","obj":"2_test"},{"subj":"T80876","pred":"source","obj":"2_test"},{"subj":"T41320","pred":"source","obj":"2_test"},{"subj":"T76033","pred":"source","obj":"2_test"},{"subj":"T26738","pred":"source","obj":"2_test"},{"subj":"T42402","pred":"source","obj":"2_test"},{"subj":"T44250","pred":"source","obj":"2_test"},{"subj":"T34124","pred":"source","obj":"2_test"},{"subj":"T33244","pred":"source","obj":"2_test"},{"subj":"T71233","pred":"source","obj":"2_test"},{"subj":"T16373","pred":"source","obj":"2_test"},{"subj":"T82064","pred":"source","obj":"2_test"},{"subj":"T2854","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93eca2","default":true}]}]}}