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Detecting signs of residual neural activity in patients with altered states of consciousness is a crucial issue for the customization of neurorehabilitation treatments and clinical decision-making. With this large observational prospective study, we propose an innovative approach to detect residual signs of consciousness via the assessment of the amount of autonomic information coded within the brain. The latter was estimated by computing the mutual information (MI) between preprocessed EEG and ECG signals, to be then compared across consciousness groups, together with the absolute power and an international qualitative labeling. One-hundred seventy-four patients (73 females, 42%) were included in the study (median age of 65 years [IQR = 20], MCS +: 29, MCS -: 23, UWS: 29). Electroencephalography (EEG) information content was found to be mostly related to the coding of electrocardiography (ECG) activity, i.e., with higher MI (p < 0.05), in Unresponsive Wakefulness Syndrome and Minimally Consciousness State minus (MCS -). EEG-ECG MI, besides clearly discriminating patients in an MCS - and +, significantly differed between lesioned areas (sides) in a subgroup of unilateral hemorrhagic patients. Crucially, such an accessible and non-invasive measure of residual consciousness signs was robust across electrodes and patient groups. Consequently, exiting from a strictly neuro-centric consciousness detection approach may be the key to provide complementary insights for the objective assessment of patients' consciousness levels and for the patient-specific planning of rehabilitative interventions., (© 2023. The Author(s).)

Background: The MRI incidental finding in asymptomatic subjects of brain white matter (WM) changes meeting the Barkhof criteria for the diagnosis of multiple sclerosis (MS) has been recently characterized as the radiologically isolated syndrome (RIS). This entity needs to be more specifically defined to allow risk stratification of these subjects. We used brain proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess metabolic changes in an RIS population., Methods: Twenty-three RIS subjects who were classified according to the Okuda Criteria underwent 1H-MRSI examination with a central brain (CB) volume of interest (VOI) to measure levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr) in the whole CB-VOI, in lesional/perilesional and normal-appearing WM regions, and in the cortical gray matter (CGM). The 1H-MRSI data were compared with those of 20 demographically matched healthy controls (HC)., Results: NAA/Cr levels were significantly lower in RIS than in HC in all regions (p < 0.005 for all). No differences in Cho/Cr levels were found in either brain region. A single-subject analysis showed that NAA/Cr levels were at least 2 SDs below the HC mean in the 44% of RIS in the normal-appearing WM and in the 61% of RIS in the CGM., Conclusion: Decreased brain NAA/Cr levels in a group of RIS subjects indicates that brain metabolic abnormalities suggestive of axonal damage can be significant even at this early disease stage. This information could be useful for stratifying RIS individuals with a high risk of progression to MS.

Background and Purpose: The development of treatment strategies for cognitive impairment in multiple sclerosis (MS) is still in its infancy. The objective of this prospective, non-randomized, pilot study was to assess the possible efficacy of treatment with natalizumab in comparison with interferon beta (IFNB) in a group of relapsing-remitting patients with MS., Methods: We included 12 patients treated with natalizumab and 14 with IFNB. At baseline and at follow-up, cognitive functioning was assessed through Rao's Brief Repeatable Battery. All the patients underwent brain MR study with the assessment of T2 lesion volumes, neocortical volume, normalized brain volume and percentage brain volume change (PBVC). Evolution of cognitive performance was assessed using available normative data for the Italian population. Treatment comparisons were assessed through the Mann-Whitney U-test, anova for repeated measures and linear multivariate regression analyses., Results: After a mean follow-up of 1.5 years, the mean number of neuropsychological tests with a deteriorating performance was significantly lower in patients treated with natalizumab (0.7 ± 0.7 vs. 1.7 ± 1.4; P = 0.031). Likewise, PBVC was significantly lower in natalizumab-treated subjects than that observed in patients treated with IFNB (-0.51% ± 0.47% vs. -1.18% ± 0.98%; P = 0.050)., Conclusion: Our results suggest a potential beneficial effect of natalizumab therapy on cognitive functioning in MS, possibly mediated by a reduction of brain atrophy., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) was hypothesized to play a causative role in multiple sclerosis (MS). The assessment of pediatric-onset MS (POMS) may provide a unique window of opportunity to study hypothesized risk factors in close temporal association with the onset of the disease., Methods: Internal jugular veins, vertebral veins and intracranial veins were evaluated with extracranial and intracranial ultrasound in 15 POMS and 16 healthy controls. Assessor's blinding was maintained during the study. We considered subjects positive to CCSVI when at least two criteria were fulfilled., Results: CCSVI frequency was comparable between POMS and controls (p > 0.05). Clinical features were not significantly different between CCSVI-positive and CCSVI-negative patients., Conclusions: Our findings add to previous data pointing against a causative role of CCSVI in MS.

Objective: To assess the relationship between cognition and brain white matter (WM) lesion distribution and frequency in patients with relapsing-remitting multiple sclerosis (RR MS)., Methods: MRI-based T2 lesion probability map (LPM) was used to assess the relevance of brain lesion location for cognitive impairment in a group of 142 consecutive patients with RRMS. Significance of voxelwise analyses was p<0.05, cluster-corrected for multiple comparisons. The Rao Brief Repeatable Battery was administered at the time of brain MRI to categorize the MS population into cognitively preserved (CP) and cognitively impaired (CI)., Results: Out of 142 RRMS, 106 were classified as CP and 36 as CI. Although the CI group had greater WM lesion volume than the CP group (p = 0.001), T2 lesions tended to be less widespread across the WM. The peak of lesion frequency was almost twice higher in CI (61% in the forceps major) than in CP patients (37% in the posterior corona radiata). The voxelwise analysis confirmed that lesion frequency was higher in CI than in CP patients with significant bilateral clusters in the forceps major and in the splenium of the corpus callosum (p<0.05, corrected). Low scores of the Symbol Digit Modalities Test correlated with higher lesion frequency in these WM regions., Conclusions: Overall these results suggest that in MS patients, areas relevant for cognition lie mostly in the commissural fiber tracts. This supports the notion of a functional (multiple) disconnection between grey matter structures, secondary to damage located in specific WM areas, as one of the most important mechanisms leading to cognitive impairment in MS.

Cognitive dysfunction involves 40-65% of multiple sclerosis patients and can have a great functional impact. It can be detected in all the disease phenotypes since the early stages of the disease, and tends to progress over time. Memory, complex attention, information-processing speed and executive functions are most commonly involved. The relationship between cognitive changes and magnetic resonance imaging (MRI) findings may involve changes in different areas, including white matter lesions, cortical and deep grey matter and normal appearing brain tissue on conventional MRI. The search for effective therapeutic strategies is a major undertaking, involving the use of both pharmacologic and rehabilitative approaches. Early treatment with disease-modifying drugs that can contain the disease burden in the brain seems to be highly advisable in order to prevent or delay the development of cognitive impairment.

Cognitive impairment can be detected in a sizeable proportion of pediatric multiple sclerosis (MS) patients. It involves memory, complex attention, information processing speed, executive functions, linguistic abilities, and intelligent quotient. It has a great impact on school, everyday and social activities, and significantly progresses overtime in the great majority of the subjects. These findings highlight the importance of a comprehensive and systematic assessment of MS-related cognitive difficulties in pediatric cases. Moreover, despite the acknowledged relevance of cognitive impairment in this age range, specific interventions for pediatric MS are lacking. As for rehabilitative strategies, there is some evidence of efficacy in other diseases, in particular brain trauma, tumor, and stroke. The development of effective rehabilitative strategies tailored to the needs of young MS patients is a priority for future research in the field.