Brigham and Women's Hospital
Neurology

Author Of 2 Presentations

Pathogenesis – Role of Glia Late Breaking Abstracts

LB1224 - Thalamic and whole brain atrophy are linked with white matter microglial activation: A [F-18]PBR06-PET study in multiple sclerosis  (ID 2099)

Speakers
Presentation Number
LB1224
Presentation Topic
Pathogenesis – Role of Glia

Abstract

Background

Thalamic and whole brain atrophy have been extensively studied as biomarkers of neurodegeneration in multiple sclerosis but their mechanism is not clear. [F-18]PBR06-Positron Emission Tomography (PET) is a novel molecular imaging technique to assess microglial activation.

Objectives

To determine the relationship of thalamic and whole brain atrophy with white matter (WM) microglial activation in multiple sclerosis.

Methods

22 individuals (13 MS, including 8 relapsing-remitting and 5 secondary progressive, and 9 healthy control (HC)) subjects underwent 3T MRI and [F-18]PBR06-PET. Individualized z-score maps of WM microglial activation were generated by voxel-by-voxel comparison between each subject's PET SUVR images and a control dataset. Glial activity load on PET in WM (“GALP-WM”) was calculated as the sum of voxel-by-voxel z-scores ≥4 in the WM subjects and its logarithmic transformation (“ln-GALP”) was also obtained. "Z-max" score was calculated as the highest z-score in the WM matter averaged over surrounding 5 voxels. SIENAX and FSL-FIRST pipelines determined normalized brain parenchymal volume (BPV) and thalamic volumes (Th-V) respectively. A p-value <0.05 was considered statistically significant.

Results

Th-V and BPV were lower in MS vs. HC (19.7±2.2 vs. 22.4±1.6 ml, 1376.6±81.3 vs. 1475.1±70.9 ml, both p<0.01). GALP-WM, Z-max and ln-GALP were higher in MS vs. HC (18757.9±13646 vs. 7580.5±12216, 13.2±2.9 vs. 8.3±4.1, and 9.5±0.92 vs. 7.4±1.9, all p<0.05). Th-V and BPV were inversely correlated with WM microglial activation, represented by GALP-WM, Z-max and ln-GALP (r=-0.62, -0.66 and -0.62, all p<0.01 for Th-V and r=-0.68, -0.643 and -0.678, all p<0.01 for BPV) that remained significant after adjustment for age (all p<0.05).

Conclusions

Thalamic and whole brain atrophy are linked with white matter microglial activation in MS, representing a link between neuroinflammation and neurodegeneration across central nervous system compartments. Further investigation of the “GALP” method as a novel, individualized approach for evaluating glial activity in MS is warranted. Prospective longitudinal studies to determine the impact of therapeutically targeting microglial activation on neurodegeneration in MS patients are urgently needed.

Collapse
COVID-19 Late Breaking Abstracts

LB1262 - Low Prevalence of SARS-CoV-2 Antibodies in People with Multiple Sclerosis Residing in Massachusetts (ID 2159)

Abstract

Background

Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2. Most people with multiple sclerosis (MS) are treated with immunomodulators or immunosuppressants, so it is crucial to understand the immune response to the novel SARS-CoV-2 in people with MS.

Objectives

To investigate the prevalence and persistence of the SARS-CoV-2 antibody response in MS and how this relates to MS phenotype and treatment.

Methods

227 consecutive people with MS residing in MA and receiving care at Massachusetts General Hospital or Brigham and Women’s Hospital and 143 of their cohabitants were enrolled May 29-July 23, 2020. In addition, 8 people with MS receiving care elsewhere who tested positive for SARS-CoV-2 nasal swab PCR and 7 cohabitants of that group were enrolled to enrich the sample for select analyses. Each participant remotely submitted a dried blood card for in-house MGH SARS-CoV-2 IgG ELISA assay testing. The assay displays 99.7% sensitivity and 100% specificity >14 days from symptom onset. Participants completed a REDCap questionnaire covering demographics, MS history and treatments, comorbidities, and COVID-19 symptoms and exposure. Antibody prevalence in MS participants will be compared to that in their cohabitants using Pearson’s Chi-squared tests.

Results

The majority of MS participants were characterized as relapsing/remitting (76.8%) and were taking disease modifying therapies (72.6%) at the time of collection. SARS-CoV-2 antibodies were detected in 3.5% of people with MS residing in MA and 6.3% of their cohabitants (X2=1.54, p=0.22). For comparison, ~1.5% of the MA population had tested positive by PCR in this date range. Exposure and treatment data will be presented in 13 cases of antibody discordance between the person with MS and his/her cohabitant; the person with MS was antibody-negative in 10 cases and antibody-positive in 3 cases with discordance. In total there were 6 MS participants and no cohabitants who previously tested positive by nasal swab PCR but lacked antibodies at follow-up. Of the COVID-positive participants (by PCR or antibody), 54.5% (6 of 11) of MS and 88.9% (8 of 9) of cohabitants were asymptomatic (p=0.16).

Conclusions

Antibody prevalence was low overall in people with MS residing in MA. Discordance between MS participants and their cohabitants and lack of detectable antibodies in some people with MS with prior nasal swab PCR positivity suggest SARS-CoV-2 antibodies may be less persistent in people with MS.

Collapse

Presenter Of 1 Presentation

Pathogenesis – Role of Glia Late Breaking Abstracts

LB1224 - Thalamic and whole brain atrophy are linked with white matter microglial activation: A [F-18]PBR06-PET study in multiple sclerosis  (ID 2099)

Speakers
Presentation Number
LB1224
Presentation Topic
Pathogenesis – Role of Glia

Abstract

Background

Thalamic and whole brain atrophy have been extensively studied as biomarkers of neurodegeneration in multiple sclerosis but their mechanism is not clear. [F-18]PBR06-Positron Emission Tomography (PET) is a novel molecular imaging technique to assess microglial activation.

Objectives

To determine the relationship of thalamic and whole brain atrophy with white matter (WM) microglial activation in multiple sclerosis.

Methods

22 individuals (13 MS, including 8 relapsing-remitting and 5 secondary progressive, and 9 healthy control (HC)) subjects underwent 3T MRI and [F-18]PBR06-PET. Individualized z-score maps of WM microglial activation were generated by voxel-by-voxel comparison between each subject's PET SUVR images and a control dataset. Glial activity load on PET in WM (“GALP-WM”) was calculated as the sum of voxel-by-voxel z-scores ≥4 in the WM subjects and its logarithmic transformation (“ln-GALP”) was also obtained. "Z-max" score was calculated as the highest z-score in the WM matter averaged over surrounding 5 voxels. SIENAX and FSL-FIRST pipelines determined normalized brain parenchymal volume (BPV) and thalamic volumes (Th-V) respectively. A p-value <0.05 was considered statistically significant.

Results

Th-V and BPV were lower in MS vs. HC (19.7±2.2 vs. 22.4±1.6 ml, 1376.6±81.3 vs. 1475.1±70.9 ml, both p<0.01). GALP-WM, Z-max and ln-GALP were higher in MS vs. HC (18757.9±13646 vs. 7580.5±12216, 13.2±2.9 vs. 8.3±4.1, and 9.5±0.92 vs. 7.4±1.9, all p<0.05). Th-V and BPV were inversely correlated with WM microglial activation, represented by GALP-WM, Z-max and ln-GALP (r=-0.62, -0.66 and -0.62, all p<0.01 for Th-V and r=-0.68, -0.643 and -0.678, all p<0.01 for BPV) that remained significant after adjustment for age (all p<0.05).

Conclusions

Thalamic and whole brain atrophy are linked with white matter microglial activation in MS, representing a link between neuroinflammation and neurodegeneration across central nervous system compartments. Further investigation of the “GALP” method as a novel, individualized approach for evaluating glial activity in MS is warranted. Prospective longitudinal studies to determine the impact of therapeutically targeting microglial activation on neurodegeneration in MS patients are urgently needed.

Collapse