Author Of 2 Presentations
P0138 - "Progressive Multifocal Leukoencephalopathy outcomes in Multiple Sclerosis: A Systemic review and Metanalysis " (ID 1013)
Multiple Sclerosis (MS) is an autoimmune, demyelinating disorder of the central nervous system (CNS), treated with disease modifying therapies (DMT). Although DMT are commonly well tolerated, a potentially fatal complication is progressive multifocal leukoencephalopathy (PML). PML is a severe, sometimes fatal disease of the CNS caused by the John Cunnigham virus (JCV) characterized by a wide range of neurologic deficits.
This is a systemic review and metanalysis on DMT-induced PML outcomes in MS. Literature is limited and results are not uniform due to incomplete data and various treatment protocols.
We conducted a systematic review and metanalysis of articles in PubMed, SCOPUS and EMBASE database from Jan 2005 to Dec 2019 for MS patients being treated for PML. Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of >=1.0 point from the time of PML diagnosis to post PML treatment. We categorized the PML cases into two groups - people who did not improve in the EDSS score by 1 point (EDSS-NI) versus people with improved EDSS score by at least 1 point after the PML treatment (EDSS-I).
A total of 569 articles were screened with 62 articles included with total number of patients were 214, out of which 158 were in EDSS-NI group and 36 were in EDSS-I group. A total of 129 women (66.5%) and 65 men (33.5%) participate in the study (20 cases gender were not available). The mean age of EDSS-NI was 44.7 while the mean age of EDSS-I was 40.5 (p-value: 0.021). In terms of DMT at the time of PML diagnosis, the most common DMT was natalizumab (185/214; 86.4%) followed by fingolimod (20/214; 9.3%) and others including dimethyl fumarate, ocrelizumab, alemtuzumab (9/214; 4.2%). Out of 214 cases CSF JCV DNA (copies per ml) were available in only 188 patients. In EDSS-NI group 108 cases had CSF JCV DNA >100 copies/ml (108/151; 71.5%). Whereas, in EDSS-I group 19 patients had CSF JCV DNA >100 copies/ml (19/37; 51.4%). There was significant difference in outcomes of the patients who had <100 copies/ml of CSF JCV DNA with p-value of 0.03, meaning that fewer CSF JCV DNA copies were associated with better outcomes.
The most important variables that determine outcome are age at the PML diagnosis and number of copies/ml of CSF JCV DNA. Old age and high number of copies of CSF JCV DNA are associated with worse outcome, which is either disability or death. None of the DMT are independently associated with outcome.
P0614 - Perilesional neurodegenerative injury in MS: relations with focal lesions and disability (ID 1849)
Chronic black holes (cBHs), characterized by severe myelin and axonal loss, are associated with higher disability levels in patients with multiple sclerosis (MS). However, whether cBHs impact perilesional tissue via retrograde and/or antegrade degeneration and how this remote pathology affects patient disability has not been investigated in vivo. Novel MRI techniques, such as selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment microscopic diffusion MRI spherical mean technique (SMT) have the potential to more accurately assess myelin and axonal injury in vivo, thus allowing us to measure remote tissue injury and its impact on patient clinical disability.
To compare the macromolecular-to-free pool size ratio (PSR), derived from SIR-qMT, and apparent axonal volume fraction (Vax), from SMT, values among cBHs, perilesional normal-appearing white matter (NAWM) and contra-lateral (distant) NAWM and test associations of these measures with disability in vivo.
Eighteen MS patients underwent 3T MRI consisting of clinical protocols, SIR-qMT and SMT. Regions of interest (ROIs) were manually placed on CBHs, perilesional NAWM and distant NAWM areas; PSR/Vaxwere calculated and compared using a mixed effects model. Pearson correlation analyses tested the associations between PSR/Vax values and patient clinical and MRI metrics.
Compared to perilesional NAWM, both PSR (-43.3%, p<0.001) and Vax (-29.7%, p<0.001) values were reduced in cBHs and increased in distant NAWM (10.2%, p<0.001 for PSR and 20%, p<0.001 for Vax). A strong correlation was seen for cBH and perilesional NAWM Vaxvalues (rho=0.63 p<0.001). No significant associations were seen between PSR/Vaxvalues and other clinical or MRI metrics of disease apart from cBHs PSR, which correlated with the EDSS score (rho=-0.63, p=0.03). There was a trend for decreasing PSR and Vaxvalues in all regions with worsening disease phenotype.
Our results show that myelin and axonal integrity, detected by PSR and Vax, are reduced in perilesional NAWM, as a function of the degree of focal cBH axonal injury. This is indicative of an ongoing anterograde and retrograde degeneration and suggests that preventing cBH development is a key factor for preserving NAWM integrity in surrounding tissue. PSR and Vaxlargely failed to capture associations with clinical and MRI characteristics. However, the trends observed with disease phenotypes suggest that longitudinal assessment of a larger cohort may indeed unravel the impact of this pathology on disease progression.