Delphine Wybrecht

Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis

Objective: The present study aims to determine the clinical counterpart of brain resting-state networks reorganization recently evidenced in early multiple sclerosis. Methods: Thirteen patients with early relapsing–remitting multiple sclerosis and 14 matched healthy controls were included in a resting state functional MRI study performed at 3 T. Data were analyzed using group spatial Independent Component Analysis using concatenation approach (FSL 4.1.3) and double regression analyses (SPM5) to extract local and global levels of connectivity inside various resting state networks (RSNs). Differences in global levels of connectivity of each network between patients and controls were assessed using Mann–Whitney U-test. In patients, relationship between clinical data (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Score – MSFC) and global RSN connectivity were assessed using Spearman rank correlation. Results: Independent component analysis provided eight consistent neuronal networks involved in motor, sensory and cognitive processes. For seven RSNs, the global level of connectivity was significantly increased in patients compared with controls. No significant decrease in RSN connectivity was found in early multiple sclerosis patients. MSFC values were negatively correlated with increased RSN connectivity within the dorsal frontoparietal network (r = −0.811, p = 0.001), the right ventral frontoparietal network (r = − 0.587, p = 0.045) and the prefronto-insular network (r = −0.615, p = 0.033). Conclusions: This study demonstrates that resting state networks reorganization is strongly associated with disability in early multiple sclerosis. These findings suggest that resting state functional MRI may represent a promising surrogate marker of disease burden.

Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual

Background: Previous studies have demonstrated that intrathecal synthesis of IgM is observed in multiple sclerosis (MS) and correlates with a worse disease course. These results suggest that IgM participates in the formation of MS lesions. Objective: The aim of the present study was to assess the potential association between the level of intrathecal synthesis of IgM measured after a clinically isolated syndrome (CIS) and the subsequent formation of brain lesions. Methods: Fifty seven patients with a CIS and a high risk developing MS were enrolled in a longitudinal study. Examination of cerebrospinal fluid was performed after the CIS and included measures of intrathecal IgM and IgG synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance imaging (MRI) system at baseline and after a mean follow-up period of 49 months (range 36–60). Spearman Rank correlation was used to assess the potential correlations between levels of intrathecal immunoglobulin synthesis and MRI data. Results: The level of intrathecal IgM synthesis was correlated with the number of gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain lesions during the follow-up period (p = 0.02). By taking into account brain sub-regions, we demonstrated that the level of intrathecal IgM synthesis was only correlated with the increased number of lesions in the periventricular regions (p = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI data. Conclusion: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation.

Voxelwise analysis of conventional magnetic resonance imaging to predict future disability in early relapsing–remitting multiple sclerosis

Background: The ability of conventional magnetic resonance imaging (MRI) to predict subsequent physical disability and cognitive deterioration after a clinically isolated syndrome (CIS) is weak. Objectives: We aimed to investigate whether conventional MRI changes over 1 year could predict cognitive and physical disability 5 years later in CIS. We performed analyses using a global approach (T2 lesion load, number of T2 lesions), but also a topographic approach. Methods: This study included 38 patients with a CIS. At inclusion, 10 out of 38 patients fulfilled the 2010 revised McDonald’s criteria for the diagnosis of multiple sclerosis. Expanded Disability Status Scale (EDSS) evaluation was performed at baseline, year 1 and year 5, and cognitive evaluation at baseline and year 5. T2-weighted MRI was performed at baseline and year 1. We used voxelwise analysis to analyse the predictive value of lesions location for subsequent disability. Results: Using the global approach, no correlation was found between MRI and clinical data. The occurrence or growth of new lesions in the brainstem was correlated with EDSS changes over the 5 years of follow-up. The occurrence or growth of new lesions in cerebellum, thalami, corpus callosum and frontal lobes over 1 year was correlated with cognitive impairment at 5 years. Conclusion: The assessment of lesion location at the first stage of multiple sclerosis may be of value to predict future clinical disability.

New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study

Objective In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. Methods EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). Results At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0–3] at Year 1 to 2.5 [range: 0–6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. Conclusion The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.

Glioblastoma Secondary to Meningioma: A Case Report and Literature Review

BACKGROUND The pathophysiologies underlying meningioma and glioma are distinct. The coexistence of those 2 lesions in the same patient is rare, and at the same location, it is even more exceptional. CASE DESCRIPTION We report a case of a 79-year-old man initially presenting with a meningioma that was treated by complete excision of the lesion. The patient had 2 relapses at the same site, in which glioblastoma was confirmed histopathologically. CONCLUSIONS Glial transformation meningiomas remain a contentious issue, with coincidental occurrence being the most prevalent explanation. Nevertheless, impairment of the same molecular signaling pathways in both tumor types suggests a common origin. Another hypothesis is that perilesional parenchymal damage from radiotherapy or surgery may lead to glial transformation in the tissues surrounding the original meningioma lesion. Further research is needed to determine if the original tumor or surgery has an oncogenic effect on the adjacent tissue.

Intravenous thrombolytic therapy for acute anterior ischemic stroke: Experience at the French Military Teaching Hospital in Toulon from 2003 to 2014

INTRODUCTION Intravenous thrombolysis with rt-PA is the key treatment for acute ischemic stroke (IS), and has largely been developed at the Military Teaching Hospital in Toulon since 2003. This report is of the results of our practices compared with those in the literature, as well as our attempts to identify factors predictive of a favorable outcome after thrombolysis. METHODS All patients treated with rt-PA for IS in the carotid territory between 2003 and 2014 were prospectively included. Disability was assessed at 3 months by modified Rankin Scale (m-RS) scores; outcome was considered unfavorable if the m-RS score was >2. Multivariate analyses were also performed to identify parameters correlating with poor and favorable outcomes. RESULTS Of the 289 patients prospectively enrolled in the study [mean initial National Institutes of Health Stroke Scale (NIHSS) score: 14.3], 52.5% had an m-RS score >2 at 3 months of follow-up. Three independent predictive factors for poor functional outcomes at the 3-month follow-up were identified: NIHSS score>12 on admission (P=0.048); NIHSS score>8 at discharge (P<0.001); and early neurological worsening within the first 24h (P=0.015). Early neurological improvement within 24h of rt-PA infusion was significantly associated with recanalization of the stroke-related occluded cerebral artery (P<0.001, r=0.37). CONCLUSION After 12 years of practice, our stroke unit has produced results similar to those of the major clinical studies in terms of safety and efficacy. High NIHSS scores on admission and a lack of neurological improvement during the first 24h of thrombolysis due to failure of early recanalization were identified as independent predictive factors of poor functional outcomes.