Changes to the septo-fornical area might play a role in the pathogenesis of anxiety in multiple sclerosis

Palotai, Miklós; Mike, Andrea; Cavallari, Michele; Strammer, Erzsebet; Orsi, G.; Healy, Brian C.; Schregel, Katharina; Illés, Zsolt

doi:10.1177/1352458517711273

Cited by 23 publications

(27 citation statements)

References 35 publications

(51 reference statements)

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“…4,7–9 However, among the plethora of neuroimaging studies investigating the relationship between those structural brain abnormalities and fatigue, only some showed significant associations, while others failed to replicate those findings. 10–17 The limited replicability of these studies is likely due, at least in part, to the criteria applied to classify patients. Previous neuroimaging studies allocated MS patients into “fatigued” or “non-fatigued” group using a single time-point assessment of fatigue, which may not be adequate to summarize the fluctuating dynamics of this symptom.…”

Section: Introductionmentioning

confidence: 99%

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

2020

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Background: Magnetic resonance imaging (MRI) studies of multiple sclerosis–related fatigue had limited reproducibility. Temporal fatigue fluctuations have not been considered. Objective: To investigate whether a novel group allocation that reflects temporal dynamics of fatigue improves our ability to detect fatigue-associated structural brain abnormalities. Methods: Patient stratification based on biennial fatigue assessments: sustained fatigue (SF, n = 29, fatigued at the latest ⩾2 assessments), one time-point fatigue (1F, n = 15, fatigued at the latest, but non-fatigued at the penultimate assessment), reversible fatigue (RF, n = 31, non-fatigued at the latest assessment, but reported fatigue previously), and never fatigued (NF, n = 54). Brain parenchymal fraction (BPF) and T2 lesion volume (T2LV) were compared between these groups and were derived using a conventional, single time-point fatigued versus non-fatigued stratification. Results: The SF versus NF stratification yielded improved power. SF ( p = 0.005) and RF ( p = 0.043) showed significantly higher T2LV than NF. T2LV showed no significant differences in SF versus 1F, SF versus RF, or 1F versus RF. Fatigued versus non-fatigued patients showed significantly higher T2LV ( p = 0.030). We found no significant differences in BPF between the groups. Conclusion: Taking into account temporal fatigue dynamics increases the statistical power with respect to T2LV and may improve characterization of brain pathological correlates of MS-related fatigue.

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Section: Introductionmentioning

confidence: 99%

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

2020

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“…Several studies failed to detect significant associations between structural brain abnormalities and fatigue, altogether. 12,14–16…”

Section: Introductionmentioning

confidence: 99%

Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression

et al. 2019

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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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“…While altered connectivity between the amygdala and PFC has been well documented in several stress and anxietyrelated disorders (Tromp et al, 2012), pathological inflammatory demyelination of the septo-fornical area, has also been reported in multiple sclerosis patients with high anxiety, and suggested to contribute to its pathogenesis (Palotai et al, 2018).…”

Section: Myelin and White Matter Alterations In Stress-and Anxiety-rementioning

confidence: 99%

White Matter Plasticity in Anxiety: Disruption of Neural Network Synchronization During Threat-Safety Discrimination

Liu

Likhtik

Shereen

et al. 2020

Front. Cell. Neurosci.

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Recent evidence highlighted the importance of white matter tracts in typical and atypical behaviors. White matter dynamically changes in response to learning, stress, and social experiences. Several lines of evidence have reported white matter dysfunction in psychiatric conditions, including depression, stress-and anxiety-related disorders. The mechanistic underpinnings of these associations, however, remain poorly understood. Here, we outline an integrative perspective positing a link between aberrant myelin plasticity and anxiety. Drawing on extant literature and emerging new findings, we suggest that in anxiety, unique changes may occur in response to threat and to safety learning and the ability to discriminate between both types of stimuli. We propose that altered myelin plasticity in the neural circuits underlying these two forms of learning relates to the emergence of anxiety-related disorders, by compromising mechanisms of neural network synchronization. The clinical and translational implications of this model for anxiety-related disorders are discussed.

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Changes to the septo-fornical area might play a role in the pathogenesis of anxiety in multiple sclerosis

Abstract: Our results suggest that anxiety in MS patients may have a neuropathological substrate in the septo-fornical area, which requires further validation using larger sample size and ultra-high-field MRI in targeted prospective studies.

Cited by 23 publications

References 35 publications

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression

White Matter Plasticity in Anxiety: Disruption of Neural Network Synchronization During Threat-Safety Discrimination

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