Author Of 3 Presentations
P0122 - Ocrelizumab in patients with multiple sclerosis: A single center experience. (ID 668)
Abstract
Background
Multiple Sclerosis is a progressive demyelinating autoimmune disorder that can lead to significant morbidity and mortality. It can be either relapsing remitting i.e Relapsing Remitting Multiple Sclerosis (RRMS) or progressive in nature like Primary Progressive Multiple Sclerosis (PPMS). Several Disease Modifying Treatments (DMT) are used to treat this disorder. Ocrelizumab is a humanized CD20 monoclonal antibody which was approved for management of RRMS and PPMS in 2017. Trials such OPERA I and II as well as ORATORIO has shown improved clinical outcomes in patients with RRMS and PPMS respectively.
Objectives
We aim to study the clinical disease progression including disability scores and imaging findings such as volumetric analysis of several central structures in patients being treated with Ocrelizumab at baseline and 12 months.
Methods
We enrolled a total of 124 patients that were seen at our institute, who are currently being treated with Ocrelizumab (92 with RRMS and 32 with PPMS) between August 2017 to July 2020. Clinical data was obtained from their medical records including Expanded Disability Status Scale (EDSS) and Timed 25 Foot Walk (T25FW) at baseline and 12 months. MRI of the brain, which included T1-w, T2-w, T2-FLAIR, post gadolinium T1-MRAGE sequences were also collected. LesionQuant software, developed by CorTechs laboratory will be used to obtain volumes of the cortical gray matter, white matter, hippocampi and white matter lesion load in the periventricular, juxtacortical, infratentorial and deep cerebral white matter areas.
Results
When independent paired t- test was performed there was significant improvement in the T25FW over time (t= 3.19, n=47; p=0.003 Cohen’s d= 0.46) but no such changes were observed with the EDSS scores (t= 1.58, n= 120; p=0.118 Cohen’s d= 0.14). Means of T25FW before and after intervention were 10.98 seconds and 9.49 seconds respectively. Means of EDSS scores before and after interventions were 3.58 and 3.52 respectively. We’re currently in the process of obtaining volumetric measure of the structures mentioned above and correlating them with the clinical scales in the near future.
Conclusions
In 31 participants with PPMS, EDSS score improved in 6 (19%), was stable in 22 (71%), and deteriorated in 3 (10%). In 89 participants with RRMS, EDSS score improved in 3 (3%), was stable in 76 (86%), and deteriorated in 10 (11%). We hope to further explore the effect of medication by computing imaging features in the near future.
P0138 - "Progressive Multifocal Leukoencephalopathy outcomes in Multiple Sclerosis: A Systemic review and Metanalysis " (ID 1013)
Abstract
Background
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.
Objectives
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.
Methods
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).
Results
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.
Conclusions
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)
Abstract
Background
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.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.