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Objectives: Gradual expansion of multiple sclerosis lesions over time is known to have a significant impact on disease progression. However, accurately quantifying the volume changes in chronic lesions presents challenges due to their slow rate of progression and the need for longitudinal segmentation. Our study addresses this by estimating the expansion of chronic lesions using data collected over a 1-2 year period and exploring imaging markers that do not require longitudinal lesion segmentation., Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 42 patients with MS. Lesion expansion, stratified by the severity of tissue damage as measured by mean diffusivity change, was analysed between baseline and 48 months (Progressive Volume/Severity Index, PVSI). Central brain atrophy (CBA) and the degree of tissue loss inside chronic lesions (measured by the change of T1 intensity and mean diffusivity (MD)) were used as surrogate markers., Results: CBA measured after 2 years of follow-up estimated lesion expansion at 4 years with a high degree of accuracy (r = 0.82, p < 0.001, ROC area under the curve 0.92, sensitivity of 94 %, specificity of 85 %). Increased MD within chronic lesions measured over 2 years was strongly associated with future expansion (r = 0.77, p < 0.001, ROC area under the curve 0.87, sensitivity of 81 % and specificity of 81 %). In contrast, change in lesion T1 hypointensity poorly explained future PVSI (best sensitivity and specificity 60 % and 59 % respectively)., Interpretation: CBA and, to a lesser extent, the change in MD within chronic MS lesions, measured over a period of 2 years, can provide a reliable and sensitive estimate of the extent and severity of chronic lesion expansion., Competing Interests: Declaration of competing interest Authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To evaluate the combined effect of lesion activity and pathologic processes occurring in both chronically demyelinated lesions and normal-appearing white matter (NAWM) on brain atrophy in MS., Methods: Pre- and post-gadolinium T1, fluid attenuation inversion recovery, and diffusion tensor imaging images were acquired from 50 consecutive patients with relapsing-remitting MS (all, but one, on disease-modifying therapy) at baseline and 5 years. Brain atrophy was measured using structural image evaluation, using normalization of atrophy percent brain volume change (PBVC) analysis., Results: During follow-up, brain volume diminished by 2.0% ± 1.1%. PBVC was not associated with patient age, disease duration, sex, or type of treatment. PBVC moderately correlated with baseline lesion load ( r = -0.38, p = 0.016), but demonstrated strong association with new lesion activity ( r = -0.63, p < 0.001). Brain atrophy was also strongly linked to the increase of water diffusion within chronic MS lesions ( r = -0.62, p < 0.001). In normal-appearing white matter (NAWM), PBVC demonstrated a significant correlation with both baseline and longitudinal increase of demyelination as measured by radial diffusivity (RD, r = -0.44, p = 0.005 and r = -0.35, p = 0.026, respectively). Linear regression analysis explained 62% of the variance in PBVC. It confirmed the major role of new lesion activity ( p = 0.002, standardized beta-coefficient -0.42), whereas change in diffusivity inside chronic lesions and NAWM RD at baseline also contributed significantly ( p = 0.04 and 0.02, standardized beta-coefficient -0.31 and -0.29, respectively), increasing predictive power of the model by 55%., Conclusion: In addition to new lesion activity, progressive loss of demyelinated axons in chronic lesions and the degree of demyelination in NAWM significantly contribute to accelerated loss of brain tissue in patients with MS receiving immunomodulatory therapy., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Using diffusion tensor imaging (DTI), we examined chronic stable MS lesions, peri-lesional white matter (PLWM) and normal appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (RRMS) for evidence of progressive tissue destruction and evaluated whether diffusivity change is associated with conventional MRI parameters and clinical findings., Method: Pre- and post-gadolinium T1, T2 and DTI images were acquired from 55 consecutive RRMS patients at baseline and 42.3 ± 9.7 months later. Chronic stable T2 lesions of sufficient size were identified in 43 patients (total of 134 lesions). Diffusivity parameters such as axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) were compared at baseline and follow-up. MRI was also performed in 20 normal subjects of similar age and gender., Results: Within the core of chronic MS lesions the diffusion of water molecules significantly increased over the follow-up period, while in NAWM all diffusivity indices remained stable. Since increase of AD and RD in lesional core was highly concordant, indicating isotropic nature of diffusivity change, and considering potential effect of crossing fibers on directionally-selective indices, only MD, a directionally-independent measure, was used for further analysis. The significant increase of MD in the lesion core during the follow-up period (1.29 ± 0.19 μm 2 /ms and 1.34 ± 0.20 μm 2 /ms at baseline and follow-up respectively, P  < 0.0001) was independent of age or disease duration, total brain lesion volume or new lesion activity, lesion size or location and baseline tissue damage (T1 hypointensity). Change of MD in the lesion core, however, was associated with progressive brain atrophy ( r  = 0.47, P  = 0.002). A significant gender difference was also observed: the MD change in male patients was almost twice that of female patients (0.030 ± 0.04 μm 2 /ms and 0.058 ± 0.03 μm 2 /ms in female and male respectively, P  = 0.01). Sub-analysis of lesions with lesion-free surrounding revealed the largest MD increase in the lesion core, while MD progression gradually declined towards PLWM. MD in NAWM remained stable over the follow-up period., Conclusion: The significant increase of isotropic water diffusion in the core of chronic stable MS lesions likely reflects gradual, self-sustained tissue destruction in demyelinated white matter that is more aggressive in males.

Background: Radial Diffusivity (RD) has been suggested as a promising biomarker associated with the level of myelination in MS lesions. However, the level of RD within the lesion is affected not only by loss of myelin sheaths, but also by the degree of tissue destruction. This may lead to exaggeration of diffusivity measures, potentially masking the effect of remyelination., Objective: To test the hypothesis that the T2 hyperintense lesion edge that extends beyond the T1 hypointense lesion core is less affected by tissue loss, and therefore a more appropriate target for imaging biomarker development targeting de- and re-myelination., Method: Pre- and post-gadolinium (Gd) enhanced T1, T2 and DTI images were acquired from 75 consecutive RRMS patients. The optic radiation (OR) was identified in individual patients using a template-based method. T2 lesions were segmented into T1-hypointense and T1-isointense areas and lesion masks intersected with the OR. Average Radial, Axial and Mean diffusivity (RD, AD and MD) and fractional anisotropy (FA) were calculated for lesions of the entire brain and the OR. In addition, Gd enhancing lesions were excluded from the analysis., Results: 86% of chronic T2 lesions demonstrated hypointense areas on T1-weighted images, which typically occupied the central part of each T2 lesion, taking about 40% of lesional volume. The T1-isointense component of the T2 lesion was most commonly seen as a peripheral ring of relatively constant thickness ("T2-rim"). While changes of diffusivity between adjacent normal appearing white matter and the "T2-rim" demonstrated a disproportionally high elevation of RD compare to AD, the increase of water diffusion was largely isointense between the "T2-rim" and T1-hypointense parts of the lesion., Conclusion: Distinct patterns of diffusivity within the central and peripheral components of MS lesions suggest that axonal loss dominates in the T1 hypointense core. The effects of de/remyelination may be more readily detected in the "T2-rim", where there is relative preservation of structural integrity. Identifying and separating those patterns has an important implication for clinical trials of both neuroprotective and, in particular, remyelinating agents.

Susac's syndrome is considered a rare differential diagnosis in the work-up of suspected multiple sclerosis. Over the last decade or so, significant advances in our understanding of Susac's syndrome mean that it can now be readily distinguished from multiple sclerosis in the majority of cases with a careful history and close attention to MR imaging. Supporting investigations such as CSF examination, fluorescein angiogram, visual field perimetry and audiology often yield important clues. In milder cases, however, diagnostic uncertainty can exist, and forme frustes of the disease are recognised. In this article, we discuss the clinical features of Susac's syndrome with emphasis on the findings and investigations that help to differentiate it from MS.

Decompression sickness can lead to neurological complications. Recovery may be studied by somatosensory evoked potentials (SEPs), which are more sensitive than normal methods of neurological examination, and by electroencephalography (EEG). The combination of EEG and SEP may be useful in differentiating among spinal, brainstem and cortical pathology.

The clinical manifestations of mitochondrial encephalomyopathy are described in four generations of a single kindred. The age of onset of major neurological disturbance varied from 3-70 years. In some patients, deafness was the only manifestation; in others, recurrent bouts of status epilepticus associated with focal neurological deficits and headache, caused severe disability or death. Examples of all three adult forms of mitochondrial encephalomyopathy: MELAS, MERFF and Kearns Sayre syndrome, were represented within the kindred. Associated features included deafness, short stature, non-insulin-dependent diabetes mellitus, migraine, peptic ulceration and severe constipation. The nt 3243 A-G MELAS mutation was detected in two members of the kindred. This study highlights the diversity of clinical expression of a mitochondrial mutation within a single kindred. [ABSTRACT FROM AUTHOR]