Grey matter atrophy is associated with disability increase in natalizumab-treated patients

Ciampi, Ethel; Pareto, Deborah; Sastre‐Garriga, Jaume; Vidal-Jordana, Ángela; Tur, Carmen; Río, Jordi; Tintoré, Mar; Auger, Cristina; Montalbán, Xavier

doi:10.1177/1352458516656808

Cited by 21 publications

(31 citation statements)

References 35 publications

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“…In contrast to previous studies, we did not detect focal gray matter atrophy by VBM (from 0 to 12 months and from 12 to 60 months), while previous studies did so . This may be well due to our small sample size.…”

Section: Discussioncontrasting

confidence: 99%

“…A trained neurologist performed clinical assessment every 3 to 6 months, including Expanded Disability Status Scale (EDSS). EDSS worsening was defined as an increase ≥1 point for baseline EDSS < 5.5 or an increase ≥.5 for baseline EDSS ≥ 5.5 …”

Section: Methodsmentioning

confidence: 99%

“…EDSS worsening was defined as an increase ࣙ1 point for baseline EDSS < 5.5 or an increase ࣙ.5 for baseline EDSS ࣙ 5.5. 6 Patients underwent MRI within 3 months after the start of NTZ therapy (baseline) and at 12, 24, 36, 48, and 60 months. Images were acquired on a 3.0 T MRI system (MAGNE-TOM Skyra, Siemens, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…In the AFFIRM trial (A Randomized, Placebo‐Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis), brain volume reduction was higher in the first year after initiation of NTZ treatment than in the second year, a phenomenon interpreted as a “pseudoatrophy” effect due to the inflammatory activity present at the onset of therapy . However, even though various studies investigated short‐ term dynamics of brain atrophy development in NTZ‐treated MS patients, long‐term data concerning brain volume changes on NTZ therapy are limited until now . The aim of this retrospective study was to investigate the evolution of brain volume changes in MS patients receiving NTZ for at least 60 months.…”

Section: Introductionmentioning

confidence: 99%

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Brain Atrophy in Natalizumab‐treated Patients with Multiple Sclerosis: A 5‐year Retrospective Study

Eisele

Szabo

Ebert

et al. 2018

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Studies demonstrated a higher brain volume loss in the first year after initiation of natalizumab treatment than in the second year, but the experiences beyond 24 months are scarce until now. We investigated the evolution of brain volume changes in multiple sclerosis (MS) patients receiving natalizumab for at least 60 months. METHODS Using annual 3‐dimensional magnetization‐prepared rapid acquisition gradient‐echo (MPRAGE) sequences acquired on a 3 Tesla magnetic resonance imaging (MRI), we investigated percentage brain volume changes (PBVCs) in 10 MS patients (9 women, mean age at baseline MRI = 29 ± 9 years; median Expanded Disability Status Scale = 2 ± 1.5; mean disease duration = 6 ± 5 years) after 12, 24, 36, 48, and 60 months. RESULTS PBVCs were statistically higher during the first 12 months (−1.48 ± 1.05%) when compared to 12‐24 months (−.6 ± .61%; P < .05), but not between 12‐24 and 24‐36 months (−.43 ± .54%), 24‐36 and 36‐48 months (−.28 ± .49%), and 36‐48 and 48‐60 months (−.33 ± .49%; P > .05 for all comparisons). CONCLUSION Our results contribute to the increasing knowledge of PBVCs in natalizumab‐treated MS patients. Our data suggests that after a significant PBVC decrease in the first year, brain atrophy rates show a slowdown during long‐term follow‐up.

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Section: Discussioncontrasting

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brain Atrophy in Natalizumab‐treated Patients with Multiple Sclerosis: A 5‐year Retrospective Study

Eisele

Szabo

Ebert

et al. 2018

Journal of Neuroimaging

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“…Previous studies using VBM to analyze the effect of disease‐modifying drugs have reported GM atrophy of 1.25% per year after one year of treatment with natalizumab (Ciampi et al., 2017). Comparatively, we observed GM loss of 0.5% per year in the estriol + GA group compared to 1.5% per year in the placebo + GA group after one year of treatment.…”

Section: Discussionmentioning

confidence: 99%

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

et al. 2018

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IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

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Brain atrophy patterns in multiple sclerosis patients treated with natalizumab and its clinical correlates

et al. 2022

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Background: Multiple sclerosis (MS) is defined as a demyelinating disorder of the central nervous system, witnessing over the past years a remarkable progress in the therapeutic approaches of the inflammatory process. Yet, the ongoing neurodegenerative process is still ambiguous, under-assessed, and probably under-treated. Atrophy and cognitive dysfunction represent the radiological and clinical correlates of such process. In this study, we evaluated the effect of one specific MS treatment, which is natalizumab (NTZ), on brain atrophy evolution in different anatomical regions and its correlation with the cognitive profile and the physical disability. Methods:We recruited 20 patients diagnosed with relapsing-remitting MS (RR-MS) and treated with NTZ. We tracked brain atrophy in different anatomical structures using MRI scans processed with an automated image segmentation technique. We also assessed the progression of physical disability and the cognitive function and its link with the progression of atrophy.Results: During the first 2 years of treatment, a significant volume loss was noted within the corpus callosum and the cerebellum gray matter (GM). The annual atrophy rate of the cortical GM, the cerebellum GM, the thalamus, the amygdala, the globus pallidus, and the hippocampus correlated with greater memory impairment. As for the third and fourth years of treatment, a significant atrophy revolved around the gray matter, mainly the cortical one. We also noted an increase of the thalamus volume. Conclusion:Atrophy in RR-MS patients treated with NTZ is regional and targeting highly cognitive regions mainly of the subcortical gray matter and the cerebellum. The cerebellum atrophy was a marker of physical disability progression. NTZ did not accelerate the atrophy process in MS and may play a neuroprotective role by increasing the thalamus volume.

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Grey matter atrophy is associated with disability increase in natalizumab-treated patients

Abstract: BVL develops mainly during the first year of natalizumab therapy. GM changes are independent of baseline inflammation and correlate with disability.

Cited by 21 publications

References 35 publications

Brain Atrophy in Natalizumab‐treated Patients with Multiple Sclerosis: A 5‐year Retrospective Study

Brain Atrophy in Natalizumab‐treated Patients with Multiple Sclerosis: A 5‐year Retrospective Study

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

Brain atrophy patterns in multiple sclerosis patients treated with natalizumab and its clinical correlates

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