Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load

Background: Fatigue in multiple sclerosis (MS) has been inconsistently associated with disruption of specific brain circuitries. Temporal fluctuations of fatigue have not been considered. Objective: The aim of this study was to investigate the association of fatigue with brain diffusion abnormalities, using robust criteria for patient stratification based on longitudinal patterns of fatigue. Methods: Patient stratification: (1) sustained fatigue (SF, n = 26): latest two Modified Fatigue Impact Scale (MFIS) ⩾ 38; (2) reversible fatigue (RF, n = 25): latest MFIS < 38 and minimum one previous MFIS ⩾ 38; and (3) never fatigued (NF, n = 42): MFIS always < 38 (five assessments minimum). 3T brain magnetic resonance imaging (MRI) was used to perform voxel-wise comparison of fractional anisotropy (FA) between the groups controlling for age, sex, disease duration, physical disability, white matter lesion load (T2LV), and depression. Results: SF and, to a lesser extent, RF patients showed lower FA in multiple brain regions compared to NF patients, independent of age, sex, disease duration, and physical disability. In cingulo-postcommissural-striato-thalamic regions, the differences in FA between SF and NF (but not between RF and NF or SF) patients were independent of T2LV, and in ventromedial prefronto-precommissuro-striatal and temporo-insular areas, independent of T2LV and depression. Conclusion: Damage to ventromedial prefronto-precommissuro-striatal and temporo-insular pathways appears to be a specific substrate of SF in MS.

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1H-MRSI evidence for cortical gray matter pathology that is independent of cerebral white matter lesion load in patients with secondary progressive multiple sclerosis

Journal of the Neurological Sciences ◽

10.1016/j.jns.2009.01.015 ◽

2009 ◽

Vol 282 (1-2) ◽

pp. 72-79 ◽

Cited By ~ 17

Author(s):

Zografos Caramanos ◽

Salvatore DiMaio ◽

Sridar Narayanan ◽

Yves Lapierre ◽

Douglas L. Arnold

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

White Matter Lesion ◽

Progressive Multiple Sclerosis ◽

Cerebral White Matter ◽

Lesion Load ◽

Secondary Progressive ◽

Cortical Gray Matter ◽

Cerebral White Matter Lesion

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Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes

Frontiers in Neurology ◽

10.3389/fneur.2020.00973 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ramona-Alexandra Todea ◽

Po-Jui Lu ◽

Mario Joao Fartaria ◽

Guillaume Bonnier ◽

Renaud Du Pasquier ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

White Matter Lesion ◽

Early Stage ◽

Lesion Load ◽

Clinical Changes

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Fatigue in multiple sclerosis is associated with the disruption of frontal and parietal pathways

Multiple Sclerosis Journal ◽

10.1177/1352458508098373 ◽

2009 ◽

Vol 15 (3) ◽

pp. 337-344 ◽

Cited By ~ 119

Author(s):

J Sepulcre ◽

JC Masdeu ◽

J Goñi ◽

G Arrondo ◽

N Vélez de Mendizábal ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Gray Matter ◽

Parietal Lobe ◽

White Matter Lesion ◽

Lesion Load ◽

Attentional Processes ◽

Fatigue Score ◽

Gray Matter Atrophy ◽

The Right

Background Fatigue is one of the most frequent and disturbing symptoms in multiple sclerosis (MS), directly affecting the patient’s quality of life. However, many questions remain unclear regarding the anatomic brain correlate of MS-related fatigue. Objective To assess the relationship between fatigue and white matter lesion location and gray matter atrophy. Methods In this study, 60 patients with MS were evaluated with the Modified Fatigue Impact Scale and magnetic resonance imaging. Location of white matter lesion was analyzed using a voxel-by-voxel lesion probability mapping approach and gray matter atrophy degree and location using an optimized voxel-based morphometry method. Results We found a correlation between lesion load and fatigue score (T2 lesion load: r = 0.415, P = 0.001; T1 lesion load r = 0.328, P = 0.011). Moreover, fatigue correlated with lesions in the right parietotemporal (periatrial area, juxtaventricular white matter deep in the parietal lobe and callosal forceps) and left frontal (middle-anterior corpus callosum, anterior cingulum and centrum semiovale of the superior and middle frontal gyri) white matter regions ( P < 0.001 in all cases). Finally, fatigue score significantly correlated with gray matter atrophy in frontal regions, specifically, the left superior frontal gyrus and bilateral middle frontal gyri ( P < 0.001 in all cases). Conclusion Our results suggest that the symptom of fatigue is associated with a disruption of brain networks involved in cognitive/attentional processes.

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Faculty Opinions recommendation of Large, nonplateauing relationship between clinical disability and cerebral white matter lesion load in patients with multiple sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13489073.14866201 ◽

2012 ◽

Author(s):

Marco Rovaris

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

White Matter Lesion ◽

Cerebral White Matter ◽

Lesion Load ◽

Cerebral White Matter Lesion

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Large, Nonplateauing Relationship Between Clinical Disability and Cerebral White Matter Lesion Load in Patients With Multiple Sclerosis

Archives of Neurology ◽

10.1001/archneurol.2011.765 ◽

2012 ◽

Vol 69 (1) ◽

pp. 89 ◽

Cited By ~ 16

Author(s):

Zografos Caramanos

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

White Matter Lesion ◽

Cerebral White Matter ◽

Lesion Load ◽

Cerebral White Matter Lesion

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Cortical morphology predicts placebo response in multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-04462-7 ◽

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.

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White matter lesion characteristics on MRI can differentiate multiple sclerosis from patent foramen ovale

Journal of the Neurological Sciences ◽

10.1016/j.jns.2021.118301 ◽

2021 ◽

Vol 429 ◽

pp. 118301

Author(s):

Gianmarco Severa ◽

Rosa Cortese ◽

Antonio Covelli ◽

Marco Battaglini ◽

Jian Zhang ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Patent Foramen Ovale ◽

White Matter Lesion ◽

Foramen Ovale

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Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

Multiple Sclerosis Journal ◽

10.1191/1352458504ms997oa ◽

2004 ◽

Vol 10 (2) ◽

pp. 188-196 ◽

Cited By ~ 57

Author(s):

Emmanuelle Cassol ◽

Jean-Philippe Ranjeva ◽

Danielle Ibarrola ◽

Claude Mékies ◽

Claude Manelfe ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Lesion Load ◽

Normal Appearing White Matter ◽

Relapsing Remitting ◽

One Year ◽

Diffusion Tensor Imaging Dti

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-mo nthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P B-0.0001). O ver the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. A lthough this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.

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