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CADASIL is the most frequent hereditary cerebral small vessel disease worldwide. The disease is responsible for a slow and progressive accumulation of cerebral ischemic insults that lead to disabling cognitive and motor symptoms at late age. Although there is currently no cure for this condition, future therapies may concern subjects only at early stage of the disease. This will raise the question of the participation of asymptomatic carriers of pathogenic NOTCH3 gene mutation in future clinical trials, which will presuppose acceptance of presymptomatic genetic diagnosis. In this study, we questioned the population at risk of CADASIL who had not undergone a diagnostic procedure yet. Based on a questionnaire survey carried out by an independent team of sociologists, we analyzed what underlies the choice of people at risk to undergo or not to undergo a genetic test, and what could constitute the tipping point that could lead people who were initially not interested in their diagnosis to have recourse to it. Our results suggest that, far from being a simple, unequivocal path, the decision-making process leading to the choice of diagnosis is initially slowed down by the need to distance oneself from the disease so that it doesn't take over one's life, and then evolves under the influence of a complex tangle between advancing age, the presence of early symptoms, and the personal relationship with uncertainty. It cannot be ruled out that the real and imminent prospect of therapy may also modify responses to this type of survey., (© 2024. The Author(s).)

Background: The immune form of thrombotic thrombocytopenic purpura (iTTP) and the hemolytic and uremic syndrome (HUS) are two major forms of thrombotic microangiopathy (TMA). Their treatment has been recently greatly improved. In this new era, both the prevalence and predictors of cerebral lesions occurring during the acute phase of these severe conditions remain poorly known., Aim: The prevalence and predictors of cerebral lesions appearing during the acute phase of iTTP and Shiga toxin-producing Escherichia coli-HUS or atypical HUS were evaluated in a prospective multicenter study., Methods: Univariate analysis was performed to report the main differences between patients with iTTP and those with HUS or between patients with acute cerebral lesions and the others. Multivariable logistic regression analysis was used to identify the potential predictors of these lesions., Results: Among 73 TMA cases (mean age 46.9 ± 16 years (range 21-87 years) with iTTP (n = 57) or HUS (n = 16), one-third presented with acute ischemic cerebral lesions on magnetic resonance imagery (MRI); two individuals also had hemorrhagic lesions. One in ten patients had acute ischemic lesions without any neurological symptom. The neurological manifestations did not differ between iTTP and HUS. In multivariable analysis, three factors predicted the occurrence of acute ischemic lesions on cerebral MRI: (1) the presence of old infarcts on cerebral MRI, (2) the level of blood pulse pressure, (3) the diagnosis of iTTP., Conclusion: At the acute phase of iTTP or HUS, both symptomatic and covert ischemic lesions are detected in one third of cases on MRI. Diagnosis of iTTP and the presence of old infarcts on MRI are associated with the occurrence of such acute lesions as well as increased blood pulse pressure, that may represent a potential target to further improve the therapeutic management of these conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: COVID-19 restrictive containment was responsible for major psychological distress and alteration of quality of life (QoL) in the general population. Their impact in a group of patients having cerebral small vessel disease (SVD) and at high risk of stroke and disability was unknown., Objective: We aimed to determine the potential psychological impact of strict containment during the COVID-19 pandemic in a sample of CADASIL patients, a rare SVD caused by NOTCH3 gene mutations., Methods: Interviews of 135 CADASIL patients were obtained just after the end of the strict containment in France. Depression, QoL and negative subjective experience of the containment were analysed, as well as predictors of posttraumatic and stressor-related manifestations, defined as an Impact Event Scale-Revised score ≥ 24, using multivariable logistic analysis., Results: Only 9% of patients showed a depressive episode. A similar proportion had significant posttraumatic and stressor-related disorder manifestations independently associated only with socio-environment factors, rather than clinical ones: living alone outside a couple (OR 7.86 (1.87-38.32), unemployment (OR 4.73 (1.17-18.70)) and the presence of 2 or more children at home (OR 6.34 (1.35-38.34)., Conclusion: Psychological impact of the containment was limited in CADASIL patients and did not appear related to the disease status. About 9% of patients presented with significant posttraumatic and stressor-related disorder manifestations which were predicted by living alone, unemployment, or exhaustion related to parental burden., (© 2023. The Author(s).)

Despite intensive investigations, about 30% of stroke cases remains of undetermined origin. After exclusion of common causes of stroke, there is a number of rare heritable and non-heritable conditions, which often remain misdiagnosed, that should be additionally considered in the diagnosis of cryptogenic stroke. The identification of these diseases requires a complex work up including detailed clinical evaluation for the detection of systemic symptoms and signs, an adequate neuroimaging assessment and a careful family history collection. The task becomes more complicated by phenotype heterogeneity since stroke could be the primary or unique manifestation of a syndrome or represent just a manifestation (sometimes minor) of a multisystem disorder. The aim of this review paper is to provide clinicians with an update on clinical and neuroradiological features and a set of practical suggestions for the diagnostic work up and management of these uncommon causes of stroke. The identification of these stroke causes is important to avoid inappropriate and expensive diagnostic tests, to establish appropriate management measures, including presymptomatic testing, genetic counseling, and, if available, therapy. Therefore, physicians should become familiar with these diseases to provide future risk assessment and family counseling., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Evaluate the prevalence of Labbé vein thrombosis (LVT) and its liability for the lesions observed in the case of associated ipsilateral transverse sinus thrombosis (TST)., Methods: MRI findings of 58 consecutive patients (≥ 18 years) with acute LVT and TST (group 1) were compared with those of 149 patients with acute TST-no LVT (group 2) observed during the same period., Results: The prevalence of LVT was 15.2%. Group 1: TST extended to sigmoid sinus in 94.8%, resulting in complete sinuses occlusion. Any lesion was observed in 81% within LV territory: swelling (n = 5, 8.6%), edema (n = 9; 15.5%), non-hemorrhagic Infarct (n = 1; 1.7%), multiple temporal lobe hemorrhages (n = 31; 53.5%), temporal lobe hematoma (n = 13; 22.4%), and pericerebral hemorrhages (n = 28; 50%). The hemorrhagic lesions were not related to dominant TST or to extensive venous thrombosis. There was a prevalence of left TST- LVT (n = 32; 55.2%) and a higher prevalence of hemorrhagic lesions in this subset (59.4%). Risk factors were also associated (p = 0.03). Group 2: the TST resulted in an occlusion of the TS: (i) complete (n = 16; 10.7%); (ii) incomplete (n = 97; 82.8%); and (iii) segmental, involving the TS before (n = 32; 21.5%) or after (n = 10; 6.7%) LV ending within the TS. No parenchymal/pericerebral lesions were associated., Conclusion: This study shows a strong association between the following: (i) the extent of thrombosis in the TS and the presence of LVT (p < 0.0001), (ii) the concomitance of LVT-TST and the presence of lesions in the LV territory and at the temporo-frontal convexity, (iii) risk factors and group 1 (p = 0.03).

Introduction: The main objectives of the present study are to assess the incidence of cerebral venous thrombosis (CVT) presenting as isolated subarachnoid hemorrhage (SAH) and to determine the occurrence of cortical venous thrombosis (CoVT)., Methods: Among 332 patients with CVT, investigated with the same CT and MR standardized protocol, 33 (10 %) presented with SAH, associated in 11 cases with hemorrhagic infarct or intracerebral hemorrhage. This study is based on 22 cases of CVT presenting as SAH in the absence of hemorrhagic brain lesion. Diagnosis of sinus thrombosis was established on T2* and magnetic resonance venography and that of CoVT on T2* sequence. Diagnostic of SAH was based on fluid-attenuated inversion recovery (FLAIR) sequence., Results: CVT involved lateral sinus in 18 patients, superior sagittal sinus in 16, and straight sinus in 1. Cortical veins were involved in all patients, in continuity with dural sinus thrombosis when present. SAH was circumscribed to few sulci in all cases and mainly localized at the convexity (21 cases). CoVT implied different areas on the same side in four patients and was bilateral in seven. There was no perimesencephalic or basal cisterns hemorrhage. Cortical swelling was present in 12 cases, associated with localized edema. All patients except one had a favorable outcome., Conclusion: This report shows that the incidence of CVT presenting as isolated SAH is evaluated to 6.4 % and that SAH is, in all cases, in the vicinity of CoVT and when dural thrombosis is present in continuity with it.

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination was performed. MRI assessment included age-related white matter changes (ARWMC) grading (mild, moderate, severe according to the Fazekas' scale), count of lacunar and non-lacunar infarcts, and global atrophy rating. Of the 633 (out of the 639 enrolled) patients with follow-up information (mean age 74.1 ± 5.0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological abnormality independently predicted transition to disability or death [HR (95 % CI) 1.53 (1.01-2.34)]. The hazard increased with increasing number of abnormalities. Among MRI lesions, only ARWMC of severe grade independently predicted disability or death [HR (95 % CI) 2.18 (1.37-3.48)]. In our cohort, presence and number of neurological examination abnormalities predicted global functional decline independent of MRI lesions typical of the aging brain and other determinants of disability in the elderly. Systematically checking for neurological examination abnormalities in older patients may be cost-effective in identifying those at risk of functional decline.

The PERFORM MRI Project was an ancillary study of the PERFORM trial. Its aim was to investigate the potential effects of terutroban in patients with atherothrombotic disorders, in comparison to aspirin, on the evolution of magnetic resonance imaging (MRI) lesions after a recent ischemic stroke or transient ischemic attack (TIA). The change in both hypointense and hyperintense lesions on the fluid attenuated inversion recovery (FLAIR) sequence, in the total brain volume and in the hippocampal volume from baseline (M1) to the final visit (M24) was assessed as well as the number of emergent microbleeds. A total of 748 patients had their MRI examination validated both at M1 and M24 during the study. At baseline, the volume of hypointense and hyperintense lesions on FLAIR images, the total brain volume, the hippocampal volume and the number of patients with microbleeds did not differ between the two groups. During follow-up, the mean volumetric increase of lesions hypointense or hyperintense on FLAIR images (from 5 to 8 %), the mean reduction of total brain volume (−0.4 %) and of hippocampal volume (−4 %), did not differ between the two treatment arms. The same parameters analysed ipsilateral to the ischaemic lesion did not differ either between the two groups. In the terutroban group, 16.3 % of patients presented with emergent microbleeds, 10.7 % in the aspirin group; this difference was not significant. In the PERFORM study, the progression of FLAIR lesions, of cerebral or hippocampal atrophy and of microbleeds did not differ between patients treated by terutroban and those treated by aspirin.

Cerebral white matter changes (WMC) are associated with motor, cognitive, mood, urinary disturbances, and disability, but little is known about the prevalence of neurological signs in patients with these brain lesions. We assessed the presence and occurrence of neurological abnormalities over a 3-year period and their possible associations with WMC in a cohort of initially non-disabled elderly subjects. Data from the multicenter Leukoaraiosis And DISability study were used. A standard neurological examination was performed at baseline and at each of the annual follow-up visits. A standard MRI scan was performed at baseline and after 3-years. WMC severity was graded as mild, moderate, or severe on the Fazekas scale, while the Rotterdam scale was used to assess progression. Infarcts and their occurrence were also assessed. Six hundred and thirty-nine non-disabled subjects were enrolled (mean age 74.1 ± 5.0, M/F: 288/351). Severe WMC at baseline were associated with gait and stance abnormalities, upper motor signs, and fingertap slowing. This effect was independent of age, sex, lacunar and non-lacunar infarcts. The occurrence of stance abnormalities, upper motor signs, primitive reflexes and fingertap slowing during the 3-year follow-up period was associated with both baseline WMC load and their progression. The occurrence of the same abnormalities plus extrapyramidal and primitive reflexes was associated with incident lacunar infarcts. In our cohort of non-disabled elders, severe WMC were associated with the presence and the occurrence of neurological signs, independently of other vascular brain lesions, confirming that these lesions have clinical relevance.

We compared the severity of white matter T2-hyperintensities (WMH) in the frontal lobe and occipital lobe using a visual MRI score in 102 patients with lobar intracerebral hemorrhage (ICH) diagnosed with possible or probable cerebral amyloid angiopathy (CAA), 99 patients with hypertension-related deep ICH, and 159 normal elderly subjects from a population-based cohort. The frontal-occipital (FO) gradient was used to describe the difference in the severity of WMH between the frontal lobe and occipital lobe. A higher proportion of subjects with obvious occipital dominant WMH (FO gradient ≤-2) was found among patients with lobar ICH than among healthy elderly subjects (FO gradient ≤-2: 13.7 vs. 5.7%, p = 0.03). Subjects with obvious occipital dominant WMH were more likely to have more WMH (p = 0.0006) and a significantly higher prevalence of the apolipoprotein E ε4 allele (45.8% vs. 19.4%, p = 0.04) than those who had obvious frontal dominant WMH. This finding is consistent with the relative predilection of CAA for posterior brain regions, and suggests that white matter lesions may preferentially occur in areas of greatest vascular pathology.