scholarly journals Cortical morphology predicts placebo response in multiple sclerosis

2019 ◽  
Author(s):  
Mariya V. Cherkasova ◽  
Jessie F. Fu ◽  
Michael Jarrett ◽  
Poljanka Johnson ◽  
Shawna Abel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cortical Thickness ◽  
Right Hemisphere ◽  
Functional Integration ◽  
Placebo Response ◽  
Small World ◽  
Lesion Load ◽  
Brain Correlates ◽  
The Right ◽  
Multiple Sclerosis Patients

ABSTRACTAlthough significant insights have been gained into the neural mechanisms of acute placebo responses, less is known about the mechanisms of longer-term placebo responses, such as those seen in clinical trials, or the interactions between these mechanisms and brain disease. We examined neuropathological and morphological brain correlates of placebo responses in a randomized clinical trial of a controversial endovascular treatment (“liberation therapy”) for multiple sclerosis. Patients were randomized to receive either balloon or sham extracranial venoplasty and followed for 48 weeks. The trial did not support therapeutic efficacy of venoplasty, but a subset of both venoplasty- and sham-treated patients reported an improvement in health-related quality of life that peaked at 12 weeks following treatment, suggesting a placebo response. Placebo responders had higher lesion activity than placebo non-responders. Although placebo responders did not differ from non-responders in terms of total normalized brain volume, regional grey or white matter volume or cortical thickness, graph theoretical analysis of cortical thickness covariance showed that placebo non-responders had a more homogenous cortical thickness topology with a more small-world-like architecture. In placebo non-responders, lesion load inversely predicted cortical thickness in primary somatosensory and motor areas, association areas, precuneus and insula, primarily in the right hemisphere. In placebo responders, lesion load was unrelated to cortical thickness. The neuropathological process in MS may result in a cortical configuration that is less suited to functional integration and less capable of generating a sustained placebo response.

scholarly journals Cortical morphology predicts placebo response in multiple sclerosis

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Mariya V. Cherkasova ◽  
Jessie F. Fu ◽  
Michael Jarrett ◽  
Poljanka Johnson ◽  
Shawna Abel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Right Hemisphere ◽  
Placebo Response ◽  
Small World ◽  
Lesion Load ◽  
Transient Improvement ◽  
Related Quality ◽  
Brain Correlates ◽  
The Right ◽  
Multiple Sclerosis Patients

AbstractDespite significant insights into the neural mechanisms of acute placebo responses, less is known about longer-term placebo responses, such as those seen in clinical trials, or their interactions with brain disease. We examined brain correlates of placebo responses in a randomized trial of a then controversial and now disproved endovascular treatment for multiple sclerosis. Patients received either balloon or sham extracranial venoplasty and were followed for 48 weeks. Venoplasty had no therapeutic effect, but a subset of both venoplasty- and sham-treated patients reported a transient improvement in health-related quality of life, suggesting a placebo response. Placebo responders did not differ from non-responders in total MRI T2 lesion load, count or location, nor were there differences in normalized brain volume, regional grey or white matter volume or cortical thickness (CT). However, responders had higher lesion activity. Graph theoretical analysis of CT covariance showed that non-responders had a more small-world-like CT architecture. In non-responders, lesion load was inversely associated with CT in somatosensory, motor and association areas, precuneus, and insula, primarily in the right hemisphere. In responders, lesion load was unrelated to CT. The neuropathological process in MS may produce in some a cortical configuration less capable of generating sustained placebo responses.

Early changes on electroencephalography in natalizumab-associated progressive multifocal leucoencephalopathy

2010 ◽  
Vol 16 (6) ◽  
pp. 749-753 ◽  
Author(s):  
Ingo Kleiter ◽  
Michael Schröder ◽  
Ralf Lürding ◽  
Gerhard Schuierer ◽  
David B Clifford ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Right Hemisphere ◽  
Jc Virus ◽  
Neuropsychological Testing ◽  
Neurological Deficits ◽  
Imaging Features ◽  
Progressive Multifocal Leucoencephalopathy ◽  
The Right ◽  
Multiple Sclerosis Patients ◽  
Virus Testing

Progressive multifocal leucoencephalopathy has become a growing concern in natalizumab-treated multiple sclerosis patients. Here, we describe a 35-year-old patient who was treated with 34 infusions of natalizumab before complaining about visual deterioration. MRI was non-diagnostic and JC virus testing initially was negative. Electroencephalography showed severe slowing of the right hemisphere, and neuropsychological testing revealed right frontal and temporal deficits. The diagnosis of progressive multifocal leucoencephalopathy was established 2 months later by typical MRI presentation and detection of JC virus DNA in the cerebrospinal fluid. Functional neurological deficits may precede imaging features and should prompt early consideration of progressive multifocal leucoencephalopathy.

scholarly journals The Right Hemisphere Planum Temporale Supports Enhanced Visual Motion Detection Ability in Deaf People: Evidence from Cortical Thickness

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Martha M. Shiell ◽  
François Champoux ◽  
Robert J. Zatorre
Keyword(s):  
Cortical Thickness ◽  
Motion Detection ◽  
Visual Motion ◽  
Right Hemisphere ◽  
Deaf People ◽  
Planum Temporale ◽  
Detection Thresholds ◽  
Temporal Area ◽  
The Right ◽  
Visual Motion Detection

After sensory loss, the deprived cortex can reorganize to process information from the remaining modalities, a phenomenon known as cross-modal reorganization. In blind people this cross-modal processing supports compensatory behavioural enhancements in the nondeprived modalities. Deaf people also show some compensatory visual enhancements, but a direct relationship between these abilities and cross-modally reorganized auditory cortex has only been established in an animal model, the congenitally deaf cat, and not in humans. Using T1-weighted magnetic resonance imaging, we measured cortical thickness in the planum temporale, Heschl’s gyrus and sulcus, the middle temporal area MT+, and the calcarine sulcus, in early-deaf persons. We tested for a correlation between this measure and visual motion detection thresholds, a visual function where deaf people show enhancements as compared to hearing. We found that the cortical thickness of a region in the right hemisphere planum temporale, typically an auditory region, was greater in deaf individuals with better visual motion detection thresholds. This same region has previously been implicated in functional imaging studies as important for functional reorganization. The structure-behaviour correlation observed here demonstrates this area’s involvement in compensatory vision and indicates an anatomical correlate, increased cortical thickness, of cross-modal plasticity.

Agreement analysis comparing iPad LCVA and Sloan testing in multiple sclerosis patients

2017 ◽  
Vol 24 (8) ◽  
pp. 1126-1130 ◽  
Author(s):  
Neda Sattarnezhad ◽  
Samantha Farrow ◽  
Dorlan Kimbrough ◽  
Bonnie Glanz ◽  
Brian Healy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Visual Acuity ◽  
T Test ◽  
Computerized Testing ◽  
Low Contrast ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
The Right ◽  
Multiple Sclerosis Patients ◽  
Paired T Test

Background: Visual symptoms are common in multiple sclerosis (MS). Low-contrast visual acuity (LCVA) testing using Sloan charts has demonstrated increased sensitivity for visual deficits compared to high-contrast acuity testing. Computerized testing of visual acuity may facilitate use in the clinic setting. Objectives: To evaluate the agreement between an iPad-based and Sloan testing of LCVA in a cohort of MS patients. Methods: A total of 38 patients with relapsing-remitting MS were enrolled after providing informed written consent at Partners MS Center, Brigham and Women’s hospital. Monocular LCVA was measured using retroilluminated Sloan chart and iPad-based LogMAR chart. Number of correct letters and agreement between two measurements were assessed for each eye using Bland–Altman analysis and paired t-test. Results: For both eyes, there was no significant difference in number correct between the two measurements using a paired t-test, and there was high correlation between two measurements (oculus dextrus (OD) r = 0.89, p < 0.001; oculus sinister (OS) r = 0.78, p < 0.001). The limits of agreement were −7.9 to +8.5 letters for the right eye and −10.9 to +11.2 letters for the left eye. Conclusion: An iPad-based LCVA test shows good agreement with Sloan testing in MS patients.

A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab

2018 ◽  
Vol 25 (6) ◽  
pp. 811-818 ◽  
Author(s):  
Irene M Vavasour ◽  
Roger Tam ◽  
David KB Li ◽  
Cornelia Laule ◽  
Carolyn Taylor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Cortical Thickness ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Water Fraction ◽  
Normal Appearing White Matter ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
Multiple Sclerosis Patients

Background: Tissue damage in both multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) are important contributors to disability and progression. Specific aspects of MS pathology can be measured using advanced imaging. Alemtuzumab is a humanised monoclonal antibody targeting CD52 developed for MS treatment. Objective: To investigate changes over 2 years of advanced magnetic resonance (MR) metrics in lesions and NAWM of MS patients treated with alemtuzumab. Methods: A total of 42 relapsing–remitting alemtuzumab-treated MS subjects were scanned for 2 years at 3 T. T1 relaxation, T2 relaxation, diffusion tensor, MR spectroscopy and volumetric sequences were performed. Mean T1 and myelin water fraction (MWF) were determined for stable lesions, new lesions and NAWM. Fractional anisotropy was calculated for the corpus callosum (CC) and N-acetylaspartate (NAA) concentration was determined from a large NAWM voxel. Brain parenchymal fraction (BPF), cortical thickness and CC area were also calculated. Results: No change in any MR measurement was found in lesions or NAWM over 24 months. BPF, cortical thickness and CC area all showed decreases in the first year followed by stability in the second year. Conclusion: Advanced MR biomarkers of myelin (MWF) and neuron/axons (NAA) show no change in NAWM over 24 months in alemtuzumab-treated MS participants.

Meeting Review: The management of multiple sclerosis in children: a European view

2010 ◽  
Vol 16 (10) ◽  
pp. 1258-1267 ◽  
Author(s):  
Angelo Ghezzi ◽  
Brenda Banwell ◽  
Alexey Boyko ◽  
Maria Pia Amato ◽  
Banu Anlar ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Significant Proportion ◽  
Open Label ◽  
Common View ◽  
High Relapse Rate ◽  
Paediatric Multiple Sclerosis ◽  
Hard Evidence ◽  
The Right ◽  
Multiple Sclerosis Patients

About 3—5% of all patients with multiple sclerosis experience the onset of their disease under the age of 16. A significant proportion of paediatric multiple sclerosis patients develop significant cognitive disturbances and persistent physical disability. The high relapse rate and the morbidity in the paediatric multiple sclerosis population has triggered the use of disease-modifying therapies that have been shown to reduce relapse rate, disease progression and cognitive decline in adult patients with multiple sclerosis. Hard evidence for the right treatment and its appropriate timing is scarce in paediatric multiple sclerosis. Nevertheless, expertise in this field has grown thanks to recent open-label trials and experience generated in specialized centres. In spring 2009, a first meeting was held in Rotterdam with clinicians from 11 European countries (one from Canada) that are all active in the management of paediatric multiple sclerosis. One of the aims was to generate a common view on the management of paediatric multiple sclerosis patients. The result of this meeting is presented here to help standardize treatment and to support clinicians with less experience in this field.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

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