Course of brain damage following malignant hypertension

Course of brain damage following malignant hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Course of brain damage following malignant hypertension Jean Sebastien Liegey, antoine cremer, Ludovic Lucas, Philippe Gosse, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4355241/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Nov, 2024 Read the published version in Journal of Human Hypertension → Version 1 posted 10 You are reading this latest preprint version Abstract Background Malignant hypertension (MHT) crisis is characterized by acute and diffuse microvascular damages, and the brain is a primary target organ. While a recent MRI study has revealed extensive and frequent cerebral injuries during the acute phase of MHT crisis, there is a scarcity of follow-up data. This study aims to address this gap by investigating the evolution of brain MRI markers following the management of the acute phase of malignant hypertension. Methods In this retrospective analysis, we examined brain MRI data from patients admitted for acute MHT between 2008 and 2022 at Bordeaux University Hospital. Eligible patients had at least one follow-up brain MRI available. A skilled operator conducted a comprehensive analysis of each brain MRI, searching for posterior reversible encephalopathy syndrome (PRES), acute stroke or cerebral hemorrhage and microangiopathy markers, blinded for clinical and demographical data. Results Among 149 patients enrolled, 104 had a brain MRI at inclusion, 47 individuals had at least one follow-up brain MRI and were included in the analysis. 72.3% were male, mean age was 48.2 ± 10.8 years and 46.8% presented blood pressure control at the time of the follow-up brain MRI. Median interval between initial and follow-up brain MRI was 228 (84–726) days. Five (10.6%) new recent strokes, 2 (4.3%) cerebral hemorrhage and 0 PRES were recorded during follow-up. On the follow-up brain MRI, more patients presented chronic lacunar infarct and/or microbleeds, in higher numbers. On the contrary, overall Fazekas score was stable in 31 patients (66.0%), improved in 15 patients (31.9%) and worsened in 1 patients (2.1%). Comparison of subgroups dichotomized according to blood pressure control or follow up duration showed no difference in brain MRI markers. Conclusion This study offers valuable insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of malignant hypertension. Our findings emphasize the dynamic nature of cerebral microvascular burden and the potential for regression of white matter hyperintensities. A better understanding of these phenomena might contribute to improved diagnosis, tailored treatment, and proactive patient care in the context of malignant hypertension. Health sciences/Health care/Medical imaging Health sciences/Diseases/Cardiovascular diseases/Hypertension Malignant hypertension brain cerebral small vessel disease MRI follow up Figures Figure 1 Figure 2 Figure 3 What is known about the topic Widespread impact: Malignant hypertension (MHT) can cause widespread microvascular damage, particularly in the brain, which is often monitored through MRI. Scarcity of data: Despite frequent cerebral involvement, there is limited follow-up data on the evolution of brain injuries in MHT patients after acute crisis management. What this study adds: New cerebrovascular events: This study documents the incidence of new cerebrovascular events and the evolution of brain MRI markers in a cohort during the follow-up period after a MHT crisis. Dynamic changes observed: It highlights the dynamic changes in brain MRI markers, revealing both deterioration and improvement, suggesting a bimodal evolution of microvascular changes. Potential for improved management: Insights from this study could lead to better diagnosis, personalized treatment strategies, and proactive patient care in MHT, emphasizing the importance of ongoing monitoring and management. INTRODUCTION Malignant hypertension (MHT) is a severe form of hypertension that has been historically neglected by the medical community, despite its potential to cause acute and diffuse microvascular damage to vital organs such as the eyes, heart, brain, and kidneys. While the incidence of MHT has remained stable over the past four decades, ranging from 1 to 7 cases per 100,000 inhabitants per year, it continues to pose a significant threat to public health ( 1 ). Cardiac, renal, and ophthalmologic lesions associated with MHT are frequently observed in more than half of the patients, particularly during the acute phase and follow-up periods ( 2 – 4 ). However, brain damage resulting from MHT has received little attention, even though neurological disorders are the second leading cause of death in this population( 5 – 8 ). Recent studies have highlighted frequent and extensive cerebral involvement in MHT patients, particularly in young hypertensive patients, resulting in severe microvascular burden and frequent recent injuries, as our team recently reported( 9 ). However, little is known about the course of these brain injuries during follow-up periods after managing the malignant hypertension crisis. Therefore, the aim of this study is to report the incidence of new cerebral injuries during follow-up after managing the malignant hypertension crisis and the evolution of several brain MRI markers of microangiopathy between the first and latest follow-up MRI, in order to provide a better understanding of the long-term effects of MHT on brain health. METHOD Study design This was a cross-sectional, observational study based on patients included in the Bordeaux Malignant Hypertensive Database from 2008 to 2022. Population The Bordeaux MHT cohort has been fully described previously( 8 ).Briefly, our European excellence center has focused on malignant hypertension since 1995. Patients are referred by either the emergency department, cardiac intensive care unit, stroke unit, intensive care units or private physicians. According to the common and most recent definitions, the diagnosis of MHT requires the association of severe arterial hypertension (> 180/110 mmHg) with either severe hypertensive retinopathy (Keith and Wagener classification stage 3 or 4), or rapid onset of at least three of the following four conditions: cardiac damage, brain damage, renal damage and thrombotic microangiopathy. The definition of target organ damage is fully described in the “HYP-MOD” proposal ( 2 ). Brain damage was defined by the presence of either posterior reversible encephalopathy syndrome (PRES), ischemic or hemorrhagic stroke, extensive white matter lesions or microbleeds before 60 years of age. Brain MRI has been used since 2008 to assess the cerebrovascular consequences of MHT independently from the results of the neurological examination. We included for this study patients with at least a second brain MRI available during the follow up after MHT crisis. According to French law and the French Data Protection Authority, the handling of these data for research purposes was declared to the Data Protection Officer of Bordeaux University Hospital. On the basis of the available documents, the ethics committee publication group of the Bordeaux University Hospital issued a favorable opinion on the publication of this research work (Opinion CE-GP-2021-03). Brain imaging Brain MRI was performed using a Philips Achieva Nova® 1.5 Tesla between 2008 and 2016, and Philips Achieva Dstream® 1.5 Tesla since December 2016.The following sequences were performed: diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted and intracranial vascular imaging (either angio-MR or time of flight). We included all the patients who had a brain MRI within 21 days following MHT diagnosis to identify acute abnormalities. The following MRI markers were recorded by a stroke neurologist: acute ischemic stroke (DWI and FLAIR positive), acute intracerebral hemorrhage (T2* and FLAIR positive), acute brain edema with extensive posterior white matter hyperintensity suggesting a PRES, chronic ischemic stroke (DWI negative-FLAIR positive), chronic intracerebral hemorrhage (T2* positive-FLAIR negative) and markers of small vessel disease: i) presence of subcortical old lacunar infarct, ii) extent and distribution (deep and periventricular) of white matter hyperintensities (WMH), iii) presence of dilated perivascular spaces and iv) presence of microbleeds. WMH were rated on FLAIR sequences using the Fazekas scale( 10 ), dilated perivascular spaces were rated according to the criteria described in Zhu et al. ( 11 ). Subcortical lacunar infarcts and microbleeds were assessed according to the Standards for Reporting Vascular changes on neuroimaging( 12 ). The severity of cerebral small vessel disease was evaluated using the previously described “Small vessel disease score” (SVD score), assigning 1 point for periventricular WMH rated Fazekas 3 or deep WMH rated 2 or 3, 1 point for the presence of at least one lacune, 1 point for dilated perivascular spaces > 10 in basal ganglia, and 1 point for the presence of at least one deep microbleed( 13 ). A significant SVD score was defined by a total score ≥ 2. Brain MRI without acute ischemic and hemorrhagic stroke, PRES and presence of microangiopathy markers were considered as “No abnormality”. “At least one brain MRI abnormality” refers to a brain MRI with any of the previous abnormalities. Follow up Patients returned 1 month after discharge to the hypertension unit and then every 3 months for 1 year and then once a year. Blood pressure level, medications and adverse event occurrence were systematically recorded. Uncontrolled hypertension was defined by elevated clinic BP (> 140/90mmHg) during the consultation at the time closest to the follow-up MRI. Brain MRI follow-up was not mandatory in the cohort, but frequently performed in case of abnormal baseline brain MRI results, at the discretion of the physician. When there was more than one brain MRI available during the follow up, only the last one was considered for this study. Analysis of the second brain MRI was carried out sequentially after the first MRI for each patient, as to record the same MRI markers as the baseline brain MRI, allowing to compare the relative evolution of these markers between the two. Subsequently, we analyzed the differences in the evolution of these MRI markers between subgroups of patients dichotomized according to their BP control status during follow-up, and according to the follow-up duration (below or above the global median follow up duration). Occurrence of neurovascular event was recorded through patients’ interrogation. Data analysis Categorical variables were expressed as percentages. Quantitative variables with a normal distribution were expressed as the mean ± standard deviation, whereas those not normally distributed were expressed as the median and interquartile range (IQR). Normality was tested using the Shapiro-Wilk test. Comparisons were performed using the χ2 test or Fisher’s exact test for categorical variables, and T-test and Mann-Whitney test for quantitative variables, as appropriate. Comparison of successive evaluation was performed with Mac Nemar test, exact fisher test and paired t-test as appropriate. For all comparisons, p < 0.05 was considered significant. All statistical analyses were conducted using SAS software version 9.4 (SAS Institute, Cary, NC, USA). RESULTS We enrolled 149 patients in the cohort between January 2008 and January 2022 (flow chart, Fig. 1 ). One hundred and four had a brain MRI during the acute phase and 47 at least a second brain MRI during the follow-up. The median delay between the two brain MRI was 228 days (84–726). There was no significant difference in the characteristics of patients with and without follow-up brain MRI (Table 1 ), but a tendency toward more frequent acute cerebral injuries at admission in the former. Follow-up brain MRI results: new cerebrovascular events (Table 2 ) Among patients with acute brain injuries at baseline, 12 patients had presented a PRES, which was absent at follow-up brain MRI. New symptomatic cerebrovascular events occurred in 7 patients (14.9%), 5 new ischemic stroke and 2 new cerebral hemorrhages. Among these 7 patients, 5 were male, median age at admission, systolic and diastolic blood pressure at follow up and follow-up duration were respectively 44 (41.5–57.5) years, 144 (125 -145.5), 90 (84–102) mmHg and 409.5 (199.5–781.5) days. Follow-up brain MRI results: Microvascular data (Table 2 ) In terms of cerebral microangiopathy, the overall Fazekas score (sum of combined periventricular and deep white matter scores) was stable in 31 patients (66%), improved in 15 patients (31.9%) and worsened in 1 patient (2.1%). Ten patients out of 47 (21.3%) showed an improvement of their overall Fazekas score by at least 2 points during the follow-up. Among the 15 patients whose leukopathy improved, 5 had presented PRES at baseline MRI. The number of lacunes remained stable in 36 patients (76.6%), and worsened in 11 patients (23.4%) with the appearance of at least one additional lacune. For microbleeds, 33 patients (70.2%) remained stable, 14 patients (29.8%) worsened and presented one or several additional microbleeds. Virchow space enlargement was stable in 41 patients (87.2%), and worsened by an additional enlargement in 4 patients (8.5%). The SVD score was stable in 32 patients (68.1%), improved in 8 patients (17%) and worsened in 7 patients (14.9%). Subgroup brain MRI analysis based on the presence or absence of blood pressure control during follow-up ( Table 3 ) At the time of the follow-up brain MRI, patients had lower blood pressure level, with 22 (46.8%) patients presenting blood pressure control. Table 3 compares the main brain MRI results inpatients with and without blood pressure control. Altogether, markers of microangiopathy (change in total Fazekas score and SVD score between the first and follow-up brain MRI) did not differ between these groups. Subgroup brain MRI analysis based on the follow-up duration (Table 4 , supplemental data) Table 4 compares the main brain MRI results in patients benefiting from a follow up below or above the median follow-up duration. Altogether, markers of microangiopathy (change in total Fazekas score and SVD score between the first and follow-up brain MRI) did not differ between these groups. DISCUSSION This study offers original insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of malignant hypertension. A significant proportion of patients (14.9%) presented a new cerebrovascular event during a median follow-up of 409.5 days. On the microvascular side, evolution was bimodal with a global deterioration in the number of lacunar infarct and microbleeds but an improvement in the Fazekas score, leading to an overall stable SVD score during follow up. White matter hyperintensities on FLAIR MRI are an underused tool for characterizing the hypertensive profile of patients, both chronic and acute. In the absence of current MRI criteria for dating these lesions, interpretation can be difficult without a reference examination. The lack of significant regression of these lesions for most patients in our cohort even as they were treated in a specialized setting reinforces the interest in primary prevention through early detection of hypertension in hypertensive patients and optimal blood pressure control in the population. Moreover, the decrease of leukopathy indicated by a decrease in the Fazekas score in a subgroup of our cohort is intriguing, as it has never been described before in cohorts of malignant hypertension patients and could have 2 mains explanations. Interestingly, a recent meta-analysis of 12,284 participants with sporadic small vessel disease also reported white matter hyperintensities volume regression documented explicitly in up to one-third of participants ( 14 ), challenging the classical notion of small vessel disease related leukopathy as permanent white matter damage( 15 ). In malignant hypertensive patients, regression of vascular injuries with adequate management has already been reported in the kidney ( 16 ). An alternative explanation for this phenomenon in our cohort could be the misclassification of typically reversible white matter hyperintensities such as PRES-related ones as small vessel disease leukopathy, as in the 15 patients showing improvement of their Fazekas score, 10 had no PRES-related finding on their baseline MRI, but could have nevertheless presented atypical PRES. Mechanisms supporting this radiological improvement, as well as its clinical and cognitive implications, will need to be studied in more detail. Future studies should aim to elucidate the mechanisms underlying this regression and explore the potential of white matter hyperintensities as a biomarker of response to treatment, especially given the fact that white matter hyperintensities predict an increased risk of stroke, dementia, and death ( 15 ). Future works should also focus on the characterization of different patterns of MRI anomalies to establish a phenotype for each cerebrovascular disease, mainly cerebral amyloïd angiopathy, CADASIL, and malignant hypertension, to improve radiological diagnostic performance and allow for better categorization in clinical studies. The radiological signs of malignant hypertension can indeed be subtle and aspecific, easily leading to wrong alternative diagnoses as cerebral amyloïd angiopathy or CADASIL. In our cohort, specific cerebral involvement of malignant hypertension was seldom considered as a diagnostic hypothesis, while alternative diagnoses were proposed in 15 patients out of 104 (14.4%) during initial patient management, including cerebral amyloïd angiopathy, CADASIL, COL4 mutations, vascular or cardiac embolization and vasculitis. An erroneous diagnosis of cerebral amyloïd angiopathy may lead to contraindications for antithrombotic treatments and impair prognosis in the presence of a strong indication such as atrial fibrillation. This highlights the need for increased awareness of malignant hypertension among neuro-radiologists to improve its detection and avoid costly specialized assessments aimed at eliminating the proposed differential diagnoses. Additionally, it would be valuable to propose a differentiation between the pattern of brain damage on MRI observed during malignant hypertension as opposed to non-malignant hypertension, and leverage the use of radiomics ( 17 , 18 ) and genomics ( 19 )as a tool for clinical correlation. This would enable clinicians to better identify malignant hypertension and differentiate it from other cerebrovascular diseases with similar presentations. Overall, the brain is a central target organ of malignant hypertension and more broadly chronic hypertension ( 20 ), and cerebral damage should be thoroughly evaluated, as well as its evolution during malignant hypertensive crisis. Conversely, the extent of damage in the brain, as assessed by leukoencephalopathy, should be an additional clue of longstanding hypertension in a patient presenting with another target organ failure of unknown origin. Moreover, our study suggests that white matter hyperintensities could be used to monitor the evolution of hypertensive disease over time. This study highlights the substantial impact of malignant hypertension on cerebral health, and is to our knowledge the first to analyze in a standardized manner the evolution of new cerebrovascular events and microangiopathy markers during the follow-up of a malignant hypertension cohort. Nevertheless, our study presented the following limits : relatively small sample size, lack of blinding to clinical evolution for the stroke neurologist reviewing imaging markers, potential bias introduced by the serial assessment of each patient’s MRI, acquisition of MRI on different machines for some patients limiting comparability, and variable duration between first and follow-up neuro-imaging. Conclusion Our findings underscore the necessity of recognizing malignant hypertension as a potential cause for acute cerebral manifestations, such as ischemic or hemorrhagic stroke, alongside severe arterial hypertension and other target organ damage. The analysis of brain MRI markers during follow-up reveals the occurrence of new cerebral injuries, offering insight into the dynamic nature of microvascular burden. Particularly intriguing is the observation of white matter hyperintensities regressing in a subset of patients, highlighting their potential as an indicator of disease progression and treatment response. These results emphasize the importance of timely diagnosis, optimal blood pressure control, and vigilant monitoring in mitigating the adverse impact of malignant hypertension on cerebral health. Declarations A cknowledgement: We thank Ray Cooke for reviewing the English in the manuscript, and Christel Baigts for editing. Source of funding: None Disclosures: The authors do not report any conflict of interest in relation with this work. References Shantsila A, Lip GYH. Malignant Hypertension Revisited-Does This Still Exist? Am J Hypertens. 2017 Jun 1;30(6):543–9. Cremer A, Amraoui F, Lip GYH, Morales E, Rubin S, Segura J, et al. From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency. 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Tables Table 1 : Demographic characteristics at baseline of patients with and without follow-up brain MRI Variable No FU brain MRI n = 57 At least 1 FU brain MRI n = 47 p Age (years) 47.9 (12.4) 48.2 (10.8) 0.88* Sex (female/male) 21/35 13/34 0.36 £ Diabetes mellitus 3 (5.3 %) 5 (10.6 %) 0.46 ¤ Hypercholesterolemia 7 (12.3 %) 10 (21.3 %) 0.22£ Active smoker 24 (42.1 %) 17 (36.2 %) 0.54£ HypertensionandTargetOrgan damage SBP at admission (mmHg) 215.7 (33.2) 211.3 (24.5) 0.46* DBP at admission (mmHg) 119.2 (19.7) 118.4 (18.6) 0.83* Severe Hypertensive retinopathy 44 (78.5 %) 31 (66 %) 0.20 £ Creatinin level (µmol/l) 124 (95 - 180) 106 (84 - 172) 0.12µ Cardiac damage 50 (89.3 %) 40 (85.1 %) 0.53£ TMA stigmata 8 (14.0 %) 12 (25.5 %) 0.14£ Neurologicalmanifestationsuponadmission Neurologic symptoms at admission 22 (38.6 %) 22 (46.8 %) 0.39 £ Acute brain injury 22 (38.6 %) 27 (57.4 %) 0.055 £ Ischemic stroke 9 (15.8 %) 10 (21.3 %) 0.44 £ Cerebral Hemorrhage 7 (12.3 %) 9 (19.1 %) 0.31 £ PRES 7 (12.3 %) 12 (25.5 %) 0.082 £ Mean SVD score 1.6 (1.1) 1.9 (1.2) 0.17* Results are expressed as average (SD), median (IQR) or number (%). FU : Follow-Up, SBP : systolic blood pressure, DBP: diastolic blood pressure, MRI: Magnetic resonance imaging, TMA : thrombotic microangiopathy, standing for elevated LDH measurement associated with low haptoglobin level. Cardiac damage stands for disproportionate left ventricular hypertrophy on echocardiography or electrocardiogram and / or cardiac biomarkers elevation (troponin and BNP). * : T-Test, £:Chi-2 test, µ:Mann-Whitney test, ¤: Fisher’s exact test Table 2 : Follow-up brain MRI findings compared to baseline brain MRI findings Variables Baseline (n=47) Latest brain MRI follow-up (n=47) p Clinical data SBP (mmHg) 211.3(24.5) 136.0 (18) < 0.01 § DBP (mmHg) 118.4 (18.6) 86.0 (12.4) < 0.01 § Blood pressure control 0 (0%) 22 (46.8%) < 0.01 ¤ Parenchymal injuries Acute brain injury 27 (54.7%) 7 (14.9%) 0.02 £ Ischemic stroke 10 (21.3 %) 5 (10.6 %) 0.25 ¤ Cerebral Hemorrhage 9 (19.1 %) 2 (4.3 %) 0.05 ¤ PRES 12 (25.5 %) 0 (0 %) < 0.01 ¤ Chronic microvascular injuries At least one chronic lacunar infarct 29 (62%) 33 (70.2%) 0.019 £ Among them. mean number of lacunar infarct 2.45 (1.72) 2.93 (2.42) 0.07§ At least one microbleed 26(55%) 28 (56%) 0.16 £ Among them. mean number of microbleeds 3.4 (2.1) 4.9 (3.9) 0.057 § Extensive WMH (Fazekas score 2 or 3) Deep Periventricular 30 (64%) 33 (70%) 24 (51%) 33 (70%) 0.034 £ 1 £ Mean SVD score SVD score 0 1 2 3 4 1.9 (1.2) 6 (13%) 13 (28%) 7 (15%) 14 (30%) 7 (15%) 2.0 (1.3) 8 (17%) 9 (19%) 9 (19%) 16 (34%) 5 (11%) 0.64 § Results are expressed as average (SD), median (IQR) or number (%). SBP : systolic blood pressure, DBP: diastolic blood pressure, MRI: Magnetic resonance imaging, PRES : posterior reversible encephalopathy syndrome, WMH : white matter hyperintensities, SVD : small vessel disease. Blood pressure control stands for systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg. Acute brain injury encompasses acute stroke, hemorrhage and/or PRES. §:paired t test, ¤:Fisher exact test, £ : Mac Nemar test Table3 :Evolution ofbrain MRI markers between first and follow-up MRI according to blood pressure control status Variables Blood pressure control (n=22) Absence of blood pressure control (n=25) p Clinical data Age at baseline (years) 49.3(10.9) 47.3 (10.7) 0.78µ Follow-up duration (days) 228 (93 – 390) 209.5(83.5 – 739.5) 0.94 $ Sex (female/male) 8/14 5/20 0.21 § SBP (mmHg) 120.9 (10.5) 149.4 (11.4) < 0.001µ DBP (mmHg) 76.1 (7.2) 94.8 (9.0) < 0.001µ New cerebrovascular event Ischemic stroke 1 (4.5%) 4 (16%) 0.35 ¤ Cerebral Hemorrhage 2 (9%) 0 (0%) 0.21 ¤ PRES 0 (0%) 0 (0%) 1¤ Evolution of microvascular data At least one chronic lacunar infarct at follow up 13 (59.1%) 20 (80 %) 0.12 § Among them, mean number of lacunar infarct 1.8 (2.1) 2.3 (2.6) 0.62 $ At least one microbleed at follow up 14 (63.6%) 15 (60%) 0.80 § Among them, mean number of microbleeds 2.9 (3.2) 1.9 (2.5) 0.47$ Total Fazekas score change 0 (-1 - 0) 0 (-1 - 0) 0.60$ Relative changes in total Fazekas score -3 -2 -1 0 + 1 1 (4.5%) 3 (13.6%) 3 (13.6%) 4 (63.6%) 1 (4.5%) 2 (8%) 4 (16%) 2 (8%) 17 (68%) 0 (0 %) SVD score change 0 ( 0 – 0 ) 0 ( 0 – 0 ) 0.55$ Relative changes in SVD score - 2 - 1 0 +1 1 (4.5%) 2 (9.1%) 17 (77.2%) 2 (9.1%) 0 (0%) 5 (20%) 15 (60%) 5 (20%) Results are expressed as number (%). SBP : systolic blood pressure. DBP: diastolic blood pressure MRI: Magnetic resonance imaging; PRES. posterior reversible encephalopathy syndrome; WMH. white matter hyperintensities; SVD: small vessel disease. Total Fazekas score stands for the addition of deep and periventricular Fazekas score. Total Fazekas / SVD score change represent the difference between the Total Fazekas / SVD score at follow up and at baseline. µ : T-Test, §:Chi-2 test, $:Mann-Whitney test, ¤:Fisher’s exact test. Regarding the mean number of lacunar infarcts and microbleeds, we chose to present data as mean (SD) because it is more informative in this situation. Nevertheless, the comparison is performed with the Mann-Whitney test because of the distribution of the data. Table 4: Evolution of brain MRI markers during follow-up according to follow-up duration Variables Below median follow up (n=24) Above median follow up (n=23) p Clinical data Age at baseline (years) 49.9 (8.7) 46.4 (12.4) 0. 10µ Follow-up duration (days) 85.6 (65.1) 880.7 (625.6) <0.001µ Sex (female/male) 9/15 4/19 0.12 § Blood pressure control 11 (45.8%) 11 (47.8%) 0.89 § New cerebrovascular event Ischemic stroke 2 ( 8.3%) 3 ( 13%) 0.67 ¤ Cerebral Hemorrhage 1 (4.2%) 1(4.3%) 1 ¤ PRES 0 (0%) 0 (0%) 1 ¤ Evolution of microvascular data At least one chronic lacunar infarct at follow up 16 (66.7%) 17 (73.9%) 0.59 § Among them, mean number of lacunar infarct 2.1 (2.1) 2.1 (2.7) 0.59 $ At least one microbleed at follow up 14 (58.3%) 15 (65.2%) 0.63§ Among them, mean number of microbleeds 3.1 (3.2) 1.7 (2.4) 0.31 $ Total Fazekas score change 0 (0 – 0) 0 (0 – 0) 0.25 $ Relative changes in total Fazekas score -3 -2 -1 0 + 1 2 (8.3%) 5 (20.8%) 3 (12.5%) 12 (50%) 1 (4.2%) 1 (4.3%) 2 (8.7%) 1 (4.3%) 18 (78.3%) 0 (0%) SVD score change 0 ( 0 – -2 ) 0 ( 0 – 0 ) 1 $ Relative changes in SVD score - 2 - 1 0 +1 1 (4.2%) 4 (16.7%) 14 (58.3%) 4 (16.7%) 0 (0%) 3 (13%) 17 (73.9%) 2 (8.7%) Results are expressed as number (%). SBP : systolic blood pressure. DBP: diastolic blood pressure MRI: Magnetic resonance imaging; PRES. posterior reversible encephalopathy syndrome; WMH. white matter hyperintensities; SVD: small vessel disease. Total Fazekas score stands for the addition of deep and periventricular Fazekas score. Total Fazekas / SVD score change represent the difference between the Total Fazekas / SVD score at follow up and at baseline. µ : T-Test, §:Chi-2 test, $:Mann-Whitney test, ¤:Fisher’s exact test Regarding the mean number of lacunar infarcts and microbleeds, we chose to present data as mean (SD) because it is more informative in this situation. Nevertheless, the comparison is performed with the Mann-Whitney test because of the distribution of the data. Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Published Journal Publication published 01 Nov, 2024 Read the published version in Journal of Human Hypertension → Version 1 posted Editorial decision: revise 19 Jul, 2024 Review # 1 received at journal 10 Jul, 2024 Review # 2 received at journal 25 Jun, 2024 Reviewer # 2 agreed at journal 24 Jun, 2024 Reviewer # 1 agreed at journal 24 Jun, 2024 Reviewers invited by journal 04 Jun, 2024 Editor assigned by journal 15 May, 2024 Submission checks completed at journal 07 May, 2024 First submitted to journal 05 May, 2024 Unknown event 02 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4355241","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":310550613,"identity":"d54c62d6-e244-4cee-9f6b-552ef21531be","order_by":0,"name":"Jean Sebastien Liegey","email":"data:image/png;base64,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","orcid":"","institution":"Bordeaux University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Jean","middleName":"Sebastien","lastName":"Liegey","suffix":""},{"id":310550614,"identity":"13f0c128-a16d-49f7-bcf1-bf6266382c2e","order_by":1,"name":"antoine cremer","email":"","orcid":"https://orcid.org/0000-0001-6197-5766","institution":"CHU de Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"antoine","middleName":"","lastName":"cremer","suffix":""},{"id":310550615,"identity":"fd392497-8c46-4050-8b98-2d5e17f347f9","order_by":2,"name":"Ludovic Lucas","email":"","orcid":"","institution":"Bordeaux University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ludovic","middleName":"","lastName":"Lucas","suffix":""},{"id":310550616,"identity":"6e37d82d-e91c-49aa-918c-ee9bd0672a3c","order_by":3,"name":"Philippe Gosse","email":"","orcid":"","institution":"Bordeaux University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Philippe","middleName":"","lastName":"Gosse","suffix":""},{"id":310550617,"identity":"3f52a4e5-4246-422c-ba7c-7f1593242bf6","order_by":4,"name":"Stephane Debeugny","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Stephane","middleName":"","lastName":"Debeugny","suffix":""},{"id":310550618,"identity":"568ec2de-3f90-40d0-b83c-40215fe7c219","order_by":5,"name":"Sebastien Rubin","email":"","orcid":"https://orcid.org/0000-0002-1246-0712","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Sebastien","middleName":"","lastName":"Rubin","suffix":""},{"id":310550619,"identity":"7cc540e9-af1c-4ccb-a2f7-731cc1fa3ba5","order_by":6,"name":"julien Doublet","email":"","orcid":"","institution":"University hospital of Bordeaux","correspondingAuthor":false,"prefix":"","firstName":"julien","middleName":"","lastName":"Doublet","suffix":""},{"id":310550620,"identity":"664d7eb2-9e45-4bdb-b32f-9660f6efbe22","order_by":7,"name":"Igor Sibon","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Igor","middleName":"","lastName":"Sibon","suffix":""},{"id":310550621,"identity":"0c5dc078-30f0-4a5f-a385-dfe67210cd14","order_by":8,"name":"ROMAIN BOULESTREAU","email":"","orcid":"","institution":"Bordeaux university hospital","correspondingAuthor":false,"prefix":"","firstName":"ROMAIN","middleName":"","lastName":"BOULESTREAU","suffix":""}],"badges":[],"createdAt":"2024-05-01 16:35:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4355241/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4355241/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41371-024-00968-5","type":"published","date":"2024-11-01T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58753636,"identity":"28e82808-563c-4cb7-adf5-2f859767a9e7","added_by":"auto","created_at":"2024-06-20 16:19:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12144,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart\u003c/p\u003e\n\u003cp\u003eMHT : Malignant Hypertension; MRI: Magnetic resonance imaging, BP : blood pressure\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4355241/v1/930db38a6dfd6288ad362b1e.png"},{"id":58753634,"identity":"01092948-d650-4b91-977f-4d0d015d7c44","added_by":"auto","created_at":"2024-06-20 16:19:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60240,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDynamic Changes in Microvascular Lesions Among 47 Patients with Malignant Hypertension according to Baseline and Follow-Up Brain MRI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe evolution of SVD score and total Fazekas score (the sum of deep and periventricular Fazekas scores, ranging from 0 to 6) was examined in 47 patients from baseline to the latest cerebral MRI. Plain arrows denote patients showing improvement in microvascular lesions (n = 15 for Total Fazekas Score, n = 8 for SVD score), while dotted arrows represent patients experiencing worsening of their microvascular lesions (n = 1 for Total Fazekas score, n = 7 for SVD score). Patients with no changes between baseline and follow-up are not depicted by arrows.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4355241/v1/56a1ca7815a72631eae3cc87.png"},{"id":58753633,"identity":"fa41d195-a3ba-497a-8dfc-8c88b8068a2d","added_by":"auto","created_at":"2024-06-20 16:19:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":413920,"visible":true,"origin":"","legend":"\u003cp\u003eFollow-up brain MRI of two patients (FLAIR sequence)\u003c/p\u003e\n\u003cp\u003ePatient 1 : A 41 years old man suffered from cerebellar hematoma in 2008, revealing a previously unknown malignant hypertension (SBP \u0026gt;200 mmHg). Other organs damage were a grade III retinopathy and left ventricular hypertrophy. On follow-up MRI in 2016, WMH showed significant regression, with a 3 points decrease in the overall Fazekas score (-2 points in the deep white matter, -1 point in the periventricular white matter). Blood pressure control was not attained in 2016.\u003c/p\u003e\n\u003cp\u003ePatient 2 : A 51 years old woman presented with hypertensive encephalopathy manifested by sudden behavior changes on June 2018. Admission BP was 220/130 mmHg. Other organs damage were a grade II retinopathy and acute renal failure. On follow-up MRI two months later, WMH load had increased by a point on the Fazekas scale in the deep white matter. Blood pressure control was achieved by that time.\u003c/p\u003e\n\u003cp\u003eMRI : Magnetic resonance imaging; FLAIR : \u0026nbsp;Fluid Attenuated Inversion Recovery; WMH, white matter hyperintensities\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4355241/v1/8d2a150a4b34d2b085a8df1c.png"},{"id":68066634,"identity":"31df9705-bea9-4d00-844f-14a3a0aa261e","added_by":"auto","created_at":"2024-11-02 07:09:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1255890,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4355241/v1/b9518772-d1ce-45c3-aaca-30a9ec83518a.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Course of brain damage following malignant hypertension","fulltext":[{"header":"What is known about the topic","content":"\u003cul\u003e\n \u003cli\u003e\u003cu\u003eWidespread impact:\u003c/u\u003e Malignant hypertension (MHT) can cause widespread microvascular damage, particularly in the brain, which is often monitored through MRI.\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eScarcity of data:\u003c/u\u003e Despite frequent cerebral involvement, there is limited follow-up data on the evolution of brain injuries in MHT patients after acute crisis management.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWhat this study adds:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cu\u003eNew cerebrovascular events:\u003c/u\u003e This study documents the incidence of new cerebrovascular events and the evolution of brain MRI markers in a cohort during the follow-up period after a MHT crisis.\u003c/li\u003e\n \u003cli\u003e\u003cu\u003eDynamic changes observed:\u003c/u\u003e It highlights the dynamic changes in brain MRI markers, revealing both deterioration and improvement, suggesting a bimodal evolution of microvascular changes.\u003c/li\u003e\n \u003cli\u003e\u003cu\u003ePotential for improved management:\u003c/u\u003e Insights from this study could lead to better diagnosis, personalized treatment strategies, and proactive patient care in MHT, emphasizing the importance of ongoing monitoring and management.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eMalignant hypertension (MHT) is a severe form of hypertension that has been historically neglected by the medical community, despite its potential to cause acute and diffuse microvascular damage to vital organs such as the eyes, heart, brain, and kidneys. While the incidence of MHT has remained stable over the past four decades, ranging from 1 to 7 cases per 100,000 inhabitants per year, it continues to pose a significant threat to public health (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCardiac, renal, and ophthalmologic lesions associated with MHT are frequently observed in more than half of the patients, particularly during the acute phase and follow-up periods (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, brain damage resulting from MHT has received little attention, even though neurological disorders are the second leading cause of death in this population(\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent studies have highlighted frequent and extensive cerebral involvement in MHT patients, particularly in young hypertensive patients, resulting in severe microvascular burden and frequent recent injuries, as our team recently reported(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, little is known about the course of these brain injuries during follow-up periods after managing the malignant hypertension crisis.\u003c/p\u003e \u003cp\u003eTherefore, the aim of this study is to report the incidence of new cerebral injuries during follow-up after managing the malignant hypertension crisis and the evolution of several brain MRI markers of microangiopathy between the first and latest follow-up MRI, in order to provide a better understanding of the long-term effects of MHT on brain health.\u003c/p\u003e"},{"header":"METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional, observational study based on patients included in the Bordeaux Malignant Hypertensive Database from 2008 to 2022.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePopulation\u003c/h2\u003e \u003cp\u003eThe Bordeaux MHT cohort has been fully described previously(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).Briefly, our European excellence center has focused on malignant hypertension since 1995. Patients are referred by either the emergency department, cardiac intensive care unit, stroke unit, intensive care units or private physicians. According to the common and most recent definitions, the diagnosis of MHT requires the association of severe arterial hypertension (\u0026gt;\u0026thinsp;180/110 mmHg) with either severe hypertensive retinopathy (Keith and Wagener classification stage 3 or 4), or rapid onset of at least three of the following four conditions: cardiac damage, brain damage, renal damage and thrombotic microangiopathy. The definition of target organ damage is fully described in the \u0026ldquo;HYP-MOD\u0026rdquo; proposal (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Brain damage was defined by the presence of either posterior reversible encephalopathy syndrome (PRES), ischemic or hemorrhagic stroke, extensive white matter lesions or microbleeds before 60 years of age.\u003c/p\u003e \u003cp\u003eBrain MRI has been used since 2008 to assess the cerebrovascular consequences of MHT independently from the results of the neurological examination. We included for this study patients with at least a second brain MRI available during the follow up after MHT crisis. According to French law and the French Data Protection Authority, the handling of these data for research purposes was declared to the Data Protection Officer of Bordeaux University Hospital. On the basis of the available documents, the ethics committee publication group of the Bordeaux University Hospital issued a favorable opinion on the publication of this research work (Opinion CE-GP-2021-03).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eBrain imaging\u003c/h2\u003e \u003cp\u003eBrain MRI was performed using a Philips Achieva Nova\u0026reg; 1.5 Tesla between 2008 and 2016, and Philips Achieva Dstream\u0026reg; 1.5 Tesla since December 2016.The following sequences were performed: diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted and intracranial vascular imaging (either angio-MR or time of flight). We included all the patients who had a brain MRI within 21 days following MHT diagnosis to identify acute abnormalities. The following MRI markers were recorded by a stroke neurologist: acute ischemic stroke (DWI and FLAIR positive), acute intracerebral hemorrhage (T2* and FLAIR positive), acute brain edema with extensive posterior white matter hyperintensity suggesting a PRES, chronic ischemic stroke (DWI negative-FLAIR positive), chronic intracerebral hemorrhage (T2* positive-FLAIR negative) and markers of small vessel disease: i) presence of subcortical old lacunar infarct, ii) extent and distribution (deep and periventricular) of white matter hyperintensities (WMH), iii) presence of dilated perivascular spaces and iv) presence of microbleeds. WMH were rated on FLAIR sequences using the Fazekas scale(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), dilated perivascular spaces were rated according to the criteria described in Zhu et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Subcortical lacunar infarcts and microbleeds were assessed according to the Standards for Reporting Vascular changes on neuroimaging(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The severity of cerebral small vessel disease was evaluated using the previously described \u0026ldquo;Small vessel disease score\u0026rdquo; (SVD score), assigning 1 point for periventricular WMH rated Fazekas 3 or deep WMH rated 2 or 3, 1 point for the presence of at least one lacune, 1 point for dilated perivascular spaces\u0026thinsp;\u0026gt;\u0026thinsp;10 in basal ganglia, and 1 point for the presence of at least one deep microbleed(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). A significant SVD score was defined by a total score\u0026thinsp;\u0026ge;\u0026thinsp;2. Brain MRI without acute ischemic and hemorrhagic stroke, PRES and presence of microangiopathy markers were considered as \u0026ldquo;No abnormality\u0026rdquo;. \u0026ldquo;At least one brain MRI abnormality\u0026rdquo; refers to a brain MRI with any of the previous abnormalities.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eFollow up\u003c/h2\u003e \u003cp\u003ePatients returned 1 month after discharge to the hypertension unit and then every 3 months for 1 year and then once a year. Blood pressure level, medications and adverse event occurrence were systematically recorded. Uncontrolled hypertension was defined by elevated clinic BP (\u0026gt;\u0026thinsp;140/90mmHg) during the consultation at the time closest to the follow-up MRI. Brain MRI follow-up was not mandatory in the cohort, but frequently performed in case of abnormal baseline brain MRI results, at the discretion of the physician. When there was more than one brain MRI available during the follow up, only the last one was considered for this study. Analysis of the second brain MRI was carried out sequentially after the first MRI for each patient, as to record the same MRI markers as the baseline brain MRI, allowing to compare the relative evolution of these markers between the two. Subsequently, we analyzed the differences in the evolution of these MRI markers between subgroups of patients dichotomized according to their BP control status during follow-up, and according to the follow-up duration (below or above the global median follow up duration). Occurrence of neurovascular event was recorded through patients\u0026rsquo; interrogation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eData analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were expressed as percentages. Quantitative variables with a normal distribution were expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, whereas those not normally distributed were expressed as the median and interquartile range (IQR). Normality was tested using the Shapiro-Wilk test. Comparisons were performed using the χ2 test or Fisher\u0026rsquo;s exact test for categorical variables, and T-test and Mann-Whitney test for quantitative variables, as appropriate. Comparison of successive evaluation was performed with Mac Nemar test, exact fisher test and paired t-test as appropriate. For all comparisons, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. All statistical analyses were conducted using SAS software version 9.4 (SAS Institute, Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eWe enrolled 149 patients in the cohort between January 2008 and January 2022 (flow chart, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One hundred and four had a brain MRI during the acute phase and 47 at least a second brain MRI during the follow-up. The median delay between the two brain MRI was 228 days (84\u0026ndash;726). There was no significant difference in the characteristics of patients with and without follow-up brain MRI (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), but a tendency toward more frequent acute cerebral injuries at admission in the former.\u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up brain MRI results: new cerebrovascular events (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003eAmong patients with acute brain injuries at baseline, 12 patients had presented a PRES, which was absent at follow-up brain MRI. New symptomatic cerebrovascular events occurred in 7 patients (14.9%), 5 new ischemic stroke and 2 new cerebral hemorrhages. Among these 7 patients, 5 were male, median age at admission, systolic and diastolic blood pressure at follow up and follow-up duration were respectively 44 (41.5\u0026ndash;57.5) years, 144 (125 -145.5), 90 (84\u0026ndash;102) mmHg and 409.5 (199.5\u0026ndash;781.5) days.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up brain MRI results: Microvascular data (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/h2\u003e \u003cp\u003eIn terms of cerebral microangiopathy, the overall Fazekas score (sum of combined periventricular and deep white matter scores) was stable in 31 patients (66%), improved in 15 patients (31.9%) and worsened in 1 patient (2.1%). Ten patients out of 47 (21.3%) showed an improvement of their overall Fazekas score by at least 2 points during the follow-up. Among the 15 patients whose leukopathy improved, 5 had presented PRES at baseline MRI. The number of lacunes remained stable in 36 patients (76.6%), and worsened in 11 patients (23.4%) with the appearance of at least one additional lacune. For microbleeds, 33 patients (70.2%) remained stable, 14 patients (29.8%) worsened and presented one or several additional microbleeds. Virchow space enlargement was stable in 41 patients (87.2%), and worsened by an additional enlargement in 4 patients (8.5%). The SVD score was stable in 32 patients (68.1%), improved in 8 patients (17%) and worsened in 7 patients (14.9%).\u003c/p\u003e \u003cp\u003e \u003cb\u003eSubgroup brain MRI analysis based on the presence or absence of blood pressure control during follow-up (\u003c/b\u003eTable \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAt the time of the follow-up brain MRI, patients had lower blood pressure level, with 22 (46.8%) patients presenting blood pressure control. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e compares the main brain MRI results inpatients with and without blood pressure control. Altogether, markers of microangiopathy (change in total Fazekas score and SVD score between the first and follow-up brain MRI) did not differ between these groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup brain MRI analysis based on the follow-up duration (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, supplemental data)\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e compares the main brain MRI results in patients benefiting from a follow up below or above the median follow-up duration. Altogether, markers of microangiopathy (change in total Fazekas score and SVD score between the first and follow-up brain MRI) did not differ between these groups.\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study offers original insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of malignant hypertension. A significant proportion of patients (14.9%) presented a new cerebrovascular event during a median follow-up of 409.5 days. On the microvascular side, evolution was bimodal with a global deterioration in the number of lacunar infarct and microbleeds but an improvement in the Fazekas score, leading to an overall stable SVD score during follow up.\u003c/p\u003e \u003cp\u003eWhite matter hyperintensities on FLAIR MRI are an underused tool for characterizing the hypertensive profile of patients, both chronic and acute. In the absence of current MRI criteria for dating these lesions, interpretation can be difficult without a reference examination. The lack of significant regression of these lesions for most patients in our cohort even as they were treated in a specialized setting reinforces the interest in primary prevention through early detection of hypertension in hypertensive patients and optimal blood pressure control in the population. Moreover, the decrease of leukopathy indicated by a decrease in the Fazekas score in a subgroup of our cohort is intriguing, as it has never been described before in cohorts of malignant hypertension patients and could have 2 mains explanations. Interestingly, a recent meta-analysis of 12,284 participants with sporadic small vessel disease also reported white matter hyperintensities volume regression documented explicitly in up to one-third of participants (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), challenging the classical notion of small vessel disease related leukopathy as permanent white matter damage(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In malignant hypertensive patients, regression of vascular injuries with adequate management has already been reported in the kidney (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). An alternative explanation for this phenomenon in our cohort could be the misclassification of typically reversible white matter hyperintensities such as PRES-related ones as small vessel disease leukopathy, as in the 15 patients showing improvement of their Fazekas score, 10 had no PRES-related finding on their baseline MRI, but could have nevertheless presented atypical PRES. Mechanisms supporting this radiological improvement, as well as its clinical and cognitive implications, will need to be studied in more detail. Future studies should aim to elucidate the mechanisms underlying this regression and explore the potential of white matter hyperintensities as a biomarker of response to treatment, especially given the fact that white matter hyperintensities predict an increased risk of stroke, dementia, and death (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFuture works should also focus on the characterization of different patterns of MRI anomalies to establish a phenotype for each cerebrovascular disease, mainly cerebral amylo\u0026iuml;d angiopathy, CADASIL, and malignant hypertension, to improve radiological diagnostic performance and allow for better categorization in clinical studies. The radiological signs of malignant hypertension can indeed be subtle and aspecific, easily leading to wrong alternative diagnoses as cerebral amylo\u0026iuml;d angiopathy or CADASIL. In our cohort, specific cerebral involvement of malignant hypertension was seldom considered as a diagnostic hypothesis, while alternative diagnoses were proposed in 15 patients out of 104 (14.4%) during initial patient management, including cerebral amylo\u0026iuml;d angiopathy, CADASIL, COL4 mutations, vascular or cardiac embolization and vasculitis. An erroneous diagnosis of cerebral amylo\u0026iuml;d angiopathy may lead to contraindications for antithrombotic treatments and impair prognosis in the presence of a strong indication such as atrial fibrillation. This highlights the need for increased awareness of malignant hypertension among neuro-radiologists to improve its detection and avoid costly specialized assessments aimed at eliminating the proposed differential diagnoses. Additionally, it would be valuable to propose a differentiation between the pattern of brain damage on MRI observed during malignant hypertension as opposed to non-malignant hypertension, and leverage the use of radiomics (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) and genomics (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)as a tool for clinical correlation. This would enable clinicians to better identify malignant hypertension and differentiate it from other cerebrovascular diseases with similar presentations. Overall, the brain is a central target organ of malignant hypertension and more broadly chronic hypertension (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and cerebral damage should be thoroughly evaluated, as well as its evolution during malignant hypertensive crisis. Conversely, the extent of damage in the brain, as assessed by leukoencephalopathy, should be an additional clue of longstanding hypertension in a patient presenting with another target organ failure of unknown origin. Moreover, our study suggests that white matter hyperintensities could be used to monitor the evolution of hypertensive disease over time.\u003c/p\u003e \u003cp\u003eThis study highlights the substantial impact of malignant hypertension on cerebral health, and is to our knowledge the first to analyze in a standardized manner the evolution of new cerebrovascular events and microangiopathy markers during the follow-up of a malignant hypertension cohort. Nevertheless, our study presented the following limits : relatively small sample size, lack of blinding to clinical evolution for the stroke neurologist reviewing imaging markers, potential bias introduced by the serial assessment of each patient\u0026rsquo;s MRI, acquisition of MRI on different machines for some patients limiting comparability, and variable duration between first and follow-up neuro-imaging.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings underscore the necessity of recognizing malignant hypertension as a potential cause for acute cerebral manifestations, such as ischemic or hemorrhagic stroke, alongside severe arterial hypertension and other target organ damage. The analysis of brain MRI markers during follow-up reveals the occurrence of new cerebral injuries, offering insight into the dynamic nature of microvascular burden. Particularly intriguing is the observation of white matter hyperintensities regressing in a subset of patients, highlighting their potential as an indicator of disease progression and treatment response. These results emphasize the importance of timely diagnosis, optimal blood pressure control, and vigilant monitoring in mitigating the adverse impact of malignant hypertension on cerebral health.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eA\u003cstrong\u003ecknowledgement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Ray Cooke for reviewing the English in the manuscript, and Christel Baigts for editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of funding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors do not report any conflict of interest in relation with this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eShantsila A, Lip GYH. Malignant Hypertension Revisited-Does This Still Exist? Am J Hypertens. 2017 Jun 1;30(6):543\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eCremer A, Amraoui F, Lip GYH, Morales E, Rubin S, Segura J, et al. From malignant hypertension to hypertension-MOD: a modern definition for an old but still dangerous emergency. Journal of Human Hypertension. 2016;30(8):463\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003evan den Born BJH, Koopmans RP, van Montfrans GA. The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension. Am J Hypertens. 2007 Aug;20(8):900\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eShantsila A, Shantsila E, Beevers DG, Lip GYH. Predictors of 5-year outcomes in malignant phase hypertension: the West Birmingham Malignant Hypertension Registry. J Hypertens. 2017 Nov;35(11):2310\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eKEITH NM, WAGENER HP, KERNOHAN JW. THE SYNDROME OF MALIGNANT HYPERTENSION. Archives of Internal Medicine. 1928 Feb 1;41(2):141\u0026ndash;88. \u003c/li\u003e\n\u003cli\u003eLip GY, Beevers M, Beevers G. The failure of malignant hypertension to decline: a survey of 24 years\u0026rsquo; experience in a multiracial population in England. J Hypertens. 1994 Nov;12(11):1297\u0026ndash;305. \u003c/li\u003e\n\u003cli\u003evan den Born BJH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother. 2019 Jan 1;5(1):37\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eRubin S, Cremer A, Boulestreau R, Rigothier C, Kuntz S, Gosse P. Malignant hypertension: diagnosis, treatment and prognosis with experience from the Bordeaux cohort. Journal of Hypertension. 2018;36(1):1\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eBoulestreau R, Lucas L, Cremer A, Debeugny S, Rubin S, Gaudissard J, et al. Neurologically asymptomatic patients frequently present cerebral injuries during malignant hypertension: a MRI study. J Hypertens. 2021 Dec 1;39(12):2463\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eFazekas F, Chawluk JB AA. MR signal abnormalities at 1.5 T in Alzheimer\u0026rsquo;s dementia and normal aging. AJR Am J Roentgenol. 1987;149(2):351-6. \u003c/li\u003e\n\u003cli\u003eZhu YC, Dufouil C, Mazoyer B, Soumar\u0026eacute; A, Ricolfi F, Tzourio C, et al. Frequency and location of dilated Virchow-Robin spaces in elderly people: A population-based 3D MR imaging study. American Journal of Neuroradiology. 2011;32(4):709\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eWardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. The Lancet Neurology. 2013;12(8):822\u0026ndash;38. \u003c/li\u003e\n\u003cli\u003eStaals J, Makin SDJ, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology. 2014;(83):1228\u0026ndash;34. \u003c/li\u003e\n\u003cli\u003eJochems ACC, Arteaga C, Chappell F, Ritakari T, Hooley M, Doubal F, et al. Longitudinal Changes of White Matter Hyperintensities in Sporadic Small Vessel Disease: A Systematic Review and Meta-analysis. Neurology. 2022 Nov 29;99(22):e2454\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eDebette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010 Jul 26;341:c3666. \u003c/li\u003e\n\u003cli\u003eAmraoui F, Bos S, Vogt L, van den Born BJ. Long-term renal outcome in patients with malignant hypertension: a retrospective cohort study. BMC Nephrology. 2012 Jul 30;13(1):71. \u003c/li\u003e\n\u003cli\u003eBretzner M, Bonkhoff AK, Schirmer MD, Hong S, Dalca AV, Donahue KL, et al. MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes. Front Neurosci. 2021;15:691244. \u003c/li\u003e\n\u003cli\u003eMin ZG, Shan HR, Xu L, Yuan DH, Sheng XX, Xie WC, et al. Diffusion tensor imaging revealed different pathological processes of white matter hyperintensities. BMC Neurol. 2021 Mar 19;21(1):128. \u003c/li\u003e\n\u003cli\u003eArmstrong NJ, Mather KA, Sargurupremraj M, Knol MJ, Malik R, Satizabal CL, et al. Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities. Stroke. 2020 Jul;51(7):2111\u0026ndash;21. \u003c/li\u003e\n\u003cli\u003eIadecola C, Yaffe K, Biller J, Bratzke LC, Faraci FM, Gorelick PB, et al. Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association. Hypertension. 2016 Dec;68(6):e67\u0026ndash;94. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 : Demographic characteristics at baseline of patients with and without follow-up brain MRI\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo FU brain MRI\u003cbr\u003e\u0026nbsp;n = 57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003eAt least 1 FU brain MRI\u003cbr\u003e\u0026nbsp;n = 47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\" valign=\"bottom\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e47.9 (12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e48.2 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.88*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\" valign=\"bottom\"\u003e\n \u003cp\u003eSex (female/male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e21/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e13/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.36 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\" valign=\"bottom\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (5.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (10.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.46 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\" valign=\"bottom\"\u003e\n \u003cp\u003eHypercholesterolemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (12.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (21.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.22\u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.61971830985915%\" valign=\"bottom\"\u003e\n \u003cp\u003eActive smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e24 (42.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 (36.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.380281690140846%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.54\u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eHypertensionandTargetOrgan damage\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eSBP at admission (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e215.7 (33.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e211.3 (24.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.46*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eDBP at admission (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e119.2 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e118.4 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.83*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eSevere Hypertensive retinopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e44 (78.5 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e31 (66 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.20 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eCreatinin level (\u0026micro;mol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e124 (95 - 180)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e106 (84 - 172)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.12\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eCardiac damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e50 (89.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e40 (85.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.53\u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eTMA stigmata\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 (14.0 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (25.5 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.14\u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003eNeurologicalmanifestationsuponadmission\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eNeurologic symptoms at admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (38.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (46.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.39 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eAcute brain injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e22 (38.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e27 (57.4 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.055 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Ischemic stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (15.8 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (21.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.44 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Cerebral Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (12.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (19.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.31 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; PRES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (12.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (25.5 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.082 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.27160493827161%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean SVD score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.280423280423282%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.6 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.044091710758376%\" valign=\"bottom\"\u003e\n \u003cp\u003e1.9 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.17*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults are expressed as average (SD), median (IQR) or number (%).\u003c/p\u003e\n\u003cp\u003eFU \u0026nbsp;: Follow-Up,\u0026nbsp;SBP : systolic blood pressure, DBP: diastolic blood pressure, MRI: Magnetic resonance imaging, TMA : thrombotic microangiopathy, standing for elevated LDH measurement associated with low haptoglobin level. Cardiac damage stands for disproportionate left ventricular hypertrophy on echocardiography or electrocardiogram and / or cardiac biomarkers elevation (troponin and BNP).\u003c/p\u003e\n\u003cp\u003e* : T-Test, \u0026pound;:Chi-2 test, \u0026micro;:Mann-Whitney test, \u0026curren;: Fisher\u0026rsquo;s exact test\u003c/p\u003e\n\u003cp\u003eTable 2 : Follow-up brain MRI findings compared to baseline brain MRI findings\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBaseline (n=47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003eLatest brain MRI follow-up\u003c/p\u003e\n \u003cp\u003e(n=47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eClinical data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e211.3(24.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e136.0 (18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.01 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e118.4 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e86.0 (12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.01 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eBlood pressure control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e22 (46.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.01 \u0026nbsp;\u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eParenchymal injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eAcute brain injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e27 (54.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e7 (14.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.02 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Ischemic stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e10 (21.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e5 (10.6 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.25 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eCerebral Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e9 (19.1 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e2 (4.3 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.05 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003ePRES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e12 (25.5 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e0 (0 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.01 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eChronic microvascular injuries\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eAt least one chronic lacunar infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e29 (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e33 (70.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.019 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003e\u0026nbsp; Among them. mean number of lacunar infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e2.45 (1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e2.93 (2.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.07\u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eAt least one microbleed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e26(55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e28 (56%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.16 \u0026pound;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eAmong them. mean number of microbleeds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e3.4 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e4.9 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.057 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eExtensive WMH (Fazekas score 2 or 3)\u003c/p\u003e\n \u003cp\u003eDeep\u003c/p\u003e\n \u003cp\u003ePeriventricular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (64%)\u003c/p\u003e\n \u003cp\u003e33 (70%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (51%)\u003c/p\u003e\n \u003cp\u003e33 (70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.034 \u0026pound;\u003c/p\u003e\n \u003cp\u003e1 \u0026pound;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"45.90163934426229%\" valign=\"top\" style=\"width: 49.0391%;\"\u003e\n \u003cp\u003eMean SVD score\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSVD score\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.672131147540984%\" valign=\"top\" style=\"width: 19.0859%;\"\u003e\n \u003cp\u003e1.9 (1.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (13%)\u003c/p\u003e\n \u003cp\u003e13 (28%)\u003c/p\u003e\n \u003cp\u003e7 (15%)\u003c/p\u003e\n \u003cp\u003e14 (30%)\u003c/p\u003e\n \u003cp\u003e7 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.94353369763206%\" valign=\"top\" style=\"width: 16.3027%;\"\u003e\n \u003cp\u003e2.0 (1.3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (17%)\u003c/p\u003e\n \u003cp\u003e9 (19%)\u003c/p\u003e\n \u003cp\u003e9 (19%)\u003c/p\u003e\n \u003cp\u003e16 (34%)\u003c/p\u003e\n \u003cp\u003e5 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.482695810564662%\" valign=\"top\"\u003e\n \u003cp\u003e0.64 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults are expressed as average (SD), median (IQR) or number (%).\u003c/p\u003e\n\u003cp\u003eSBP : systolic blood pressure, DBP: diastolic blood pressure, MRI: Magnetic resonance imaging, PRES : posterior reversible encephalopathy syndrome, WMH : white matter hyperintensities, SVD : small vessel disease. Blood pressure control stands for systolic blood pressure \u0026lt; 140 mmHg and diastolic blood pressure \u0026lt; 90 mmHg. Acute brain injury encompasses acute stroke, hemorrhage and/or PRES.\u003c/p\u003e\n\u003cp\u003e\u0026sect;:paired t test, \u0026curren;:Fisher exact test, \u0026pound; :\u0026nbsp;Mac Nemar test\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable3 :Evolution ofbrain MRI markers between first and follow-up MRI according to blood pressure control status\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003eBlood pressure control\u003c/p\u003e\n \u003cp\u003e(n=22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003eAbsence of blood pressure control\u003c/p\u003e\n \u003cp\u003e(n=25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eClinical data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eAge at baseline (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e49.3(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e47.3 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.78\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eFollow-up duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e228 (93 \u0026ndash; 390)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e209.5(83.5 \u0026ndash; 739.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.94 $\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eSex (female/male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e8/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e5/20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.21 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e120.9 (10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e149.4 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eDBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e76.1 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e94.8 (9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eNew cerebrovascular event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eIschemic stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e4 (16%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.35 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eCerebral Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e2 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.21 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003ePRES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e1\u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eEvolution of microvascular data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eAt least one chronic lacunar infarct at follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e20 (80 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.232209737827715%\" valign=\"top\"\u003e\n \u003cp\u003e0.12 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.5617977528089888%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003e\u0026nbsp;Among them, mean number of lacunar infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e1.8 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e2.3 (2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.232209737827715%\" valign=\"top\"\u003e\n \u003cp\u003e0.62 $\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.5617977528089888%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eAt least one microbleed at follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e14 (63.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e15 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.232209737827715%\" valign=\"top\"\u003e\n \u003cp\u003e0.80 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.5617977528089888%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eAmong them, mean number of microbleeds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e2.9 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e1.9 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.232209737827715%\" valign=\"top\"\u003e\n \u003cp\u003e0.47$\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.5617977528089888%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eTotal Fazekas score change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (-1 - 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e0 (-1 - 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.60$\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eRelative changes in total Fazekas score\u003c/p\u003e\n \u003cp\u003e-3\u003c/p\u003e\n \u003cp\u003e-2\u003c/p\u003e\n \u003cp\u003e-1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e+ 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003cp\u003e3 (13.6%)\u003c/p\u003e\n \u003cp\u003e3 (13.6%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;4 (63.6%)\u003c/p\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (8%)\u003c/p\u003e\n \u003cp\u003e4 (16%)\u003c/p\u003e\n \u003cp\u003e2 (8%)\u003c/p\u003e\n \u003cp\u003e17 (68%)\u003c/p\u003e\n \u003cp\u003e0 (0 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eSVD score change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e0 ( 0 \u0026ndash; 0 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e0 ( 0 \u0026ndash; 0 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e0.55$\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 41.5918%;\"\u003e\n \u003cp\u003eRelative changes in SVD score\u003c/p\u003e\n \u003cp\u003e- 2\u003c/p\u003e\n \u003cp\u003e- 1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e+1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 23.5332%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003cp\u003e17 (77.2%)\u003c/p\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 19.8457%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e5 (20%)\u003c/p\u003e\n \u003cp\u003e15 (60%)\u003c/p\u003e\n \u003cp\u003e5 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults are expressed as number (%). SBP : systolic blood pressure. DBP: diastolic blood pressure\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging; PRES. posterior reversible encephalopathy syndrome; WMH. white matter hyperintensities; SVD: small vessel disease. Total Fazekas score stands for the addition of deep and periventricular Fazekas score. Total Fazekas / SVD score change represent the difference between the Total Fazekas / SVD score at follow up and at baseline.\u003c/p\u003e\n\u003cp\u003e\u0026micro; : T-Test, \u0026sect;:Chi-2 test, $:Mann-Whitney test, \u0026curren;:Fisher\u0026rsquo;s exact test.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRegarding the mean number of lacunar infarcts and microbleeds, we chose to present data as mean (SD) because it is more informative in this situation. Nevertheless, the comparison is performed with the Mann-Whitney test because of the distribution of the data.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTable 4: Evolution of brain MRI markers during follow-up according to follow-up duration\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003eBelow median follow up\u003c/p\u003e\n \u003cp\u003e(n=24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003eAbove median follow up\u003c/p\u003e\n \u003cp\u003e(n=23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eClinical data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eAge at baseline (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e49.9 (8.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e46.4 (12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0. 10\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eFollow-up duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e85.6 (65.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e880.7 (625.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u0026micro;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eSex (female/male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e9/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e4/19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.12 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eBlood pressure control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e11 (45.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e11 (47.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.89 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eNew cerebrovascular event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eIschemic stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e2 ( 8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e3 ( 13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.67 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eCerebral Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e1(4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e1 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003ePRES\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e1 \u0026curren;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eEvolution of microvascular data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eAt least one chronic lacunar infarct at follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e16 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e17 (73.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.59 \u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Among them, mean number of lacunar infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e2.1 (2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e2.1 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.59 $\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eAt least one microbleed at follow up\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e14 (58.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e15 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.63\u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Among them, mean number of microbleeds\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e3.1 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e1.7 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.31 $\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eTotal Fazekas score change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0 \u0026ndash; 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e0 (0 \u0026ndash; 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e0.25 $\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eRelative changes in total Fazekas score\u003c/p\u003e\n \u003cp\u003e-3\u003c/p\u003e\n \u003cp\u003e-2\u003c/p\u003e\n \u003cp\u003e-1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e+ 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (8.3%)\u003c/p\u003e\n \u003cp\u003e5 (20.8%)\u003c/p\u003e\n \u003cp\u003e3 (12.5%)\u003c/p\u003e\n \u003cp\u003e12 (50%)\u003c/p\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003cp\u003e18 (78.3%)\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eSVD score change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e0 ( 0 \u0026ndash; -2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e0 ( 0 \u0026ndash; 0 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e1 $\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.89513108614232%\" valign=\"top\" style=\"width: 48.3125%;\"\u003e\n \u003cp\u003eRelative changes in SVD score\u003c/p\u003e\n \u003cp\u003e- 2\u003c/p\u003e\n \u003cp\u003e- 1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e+1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.719101123595507%\" valign=\"top\" style=\"width: 18.041%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003cp\u003e4 (16.7%)\u003c/p\u003e\n \u003cp\u003e14 (58.3%)\u003c/p\u003e\n \u003cp\u003e4 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.591760299625467%\" valign=\"top\" style=\"width: 18.709%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003cp\u003e3 (13%)\u003c/p\u003e\n \u003cp\u003e17 (73.9%)\u003c/p\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.794007490636703%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eResults are expressed as number (%). SBP : systolic blood pressure. DBP: diastolic blood pressure\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging; PRES. posterior reversible encephalopathy syndrome; WMH. white matter hyperintensities; SVD: small vessel disease. Total Fazekas score stands for the addition of deep and periventricular Fazekas score. Total Fazekas / SVD score change represent the difference between the Total Fazekas / SVD score at follow up and at baseline.\u003c/p\u003e\n\u003cp\u003e\u0026micro; : T-Test, \u0026sect;:Chi-2 test, $:Mann-Whitney test, \u0026curren;:Fisher\u0026rsquo;s exact test\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRegarding the mean number of lacunar infarcts and microbleeds, we chose to present data as mean (SD) because it is more informative in this situation. Nevertheless, the comparison is performed with the Mann-Whitney test because of the distribution of the data.\u003c/em\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-human-hypertension","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jhh","sideBox":"Learn more about [Journal of Human Hypertension](http://www.nature.com/jhh/)","snPcode":"41371","submissionUrl":"https://mts-jhh.nature.com/cgi-bin/main.plex","title":"Journal of Human Hypertension","twitterHandle":"@jhhypertension","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Malignant hypertension, brain, cerebral small vessel disease, MRI, follow up","lastPublishedDoi":"10.21203/rs.3.rs-4355241/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4355241/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMalignant hypertension (MHT) crisis is characterized by acute and diffuse microvascular damages, and the brain is a primary target organ. While a recent MRI study has revealed extensive and frequent cerebral injuries during the acute phase of MHT crisis, there is a scarcity of follow-up data. This study aims to address this gap by investigating the evolution of brain MRI markers following the management of the acute phase of malignant hypertension.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this retrospective analysis, we examined brain MRI data from patients admitted for acute MHT between 2008 and 2022 at Bordeaux University Hospital. Eligible patients had at least one follow-up brain MRI available. A skilled operator conducted a comprehensive analysis of each brain MRI, searching for posterior reversible encephalopathy syndrome (PRES), acute stroke or cerebral hemorrhage and microangiopathy markers, blinded for clinical and demographical data.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAmong 149 patients enrolled, 104 had a brain MRI at inclusion, 47 individuals had at least one follow-up brain MRI and were included in the analysis. 72.3% were male, mean age was 48.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 years and 46.8% presented blood pressure control at the time of the follow-up brain MRI. Median interval between initial and follow-up brain MRI was 228 (84\u0026ndash;726) days. Five (10.6%) new recent strokes, 2 (4.3%) cerebral hemorrhage and 0 PRES were recorded during follow-up. On the follow-up brain MRI, more patients presented chronic lacunar infarct and/or microbleeds, in higher numbers. On the contrary, overall Fazekas score was stable in 31 patients (66.0%), improved in 15 patients (31.9%) and worsened in 1 patients (2.1%). Comparison of subgroups dichotomized according to blood pressure control or follow up duration showed no difference in brain MRI markers.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study offers valuable insights into the risk of new cerebrovascular events and the evolution of brain MRI markers after managing the acute phase of malignant hypertension. Our findings emphasize the dynamic nature of cerebral microvascular burden and the potential for regression of white matter hyperintensities. A better understanding of these phenomena might contribute to improved diagnosis, tailored treatment, and proactive patient care in the context of malignant hypertension.\u003c/p\u003e","manuscriptTitle":"Course of brain damage following malignant hypertension","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 16:19:51","doi":"10.21203/rs.3.rs-4355241/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-07-19T11:36:17+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-07-10T17:40:05+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-06-25T17:27:26+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-06-24T16:13:09+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-06-24T13:49:56+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-06-04T15:25:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-15T22:57:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-07T09:20:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Human Hypertension","date":"2024-05-05T17:33:53+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2024-05-02T09:39:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-human-hypertension","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jhh","sideBox":"Learn more about [Journal of Human Hypertension](http://www.nature.com/jhh/)","snPcode":"41371","submissionUrl":"https://mts-jhh.nature.com/cgi-bin/main.plex","title":"Journal of Human Hypertension","twitterHandle":"@jhhypertension","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"85ffd79c-9db8-4ba7-b569-6388731d4ebb","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":32818302,"name":"Health sciences/Health care/Medical imaging"},{"id":32818303,"name":"Health sciences/Diseases/Cardiovascular diseases/Hypertension"}],"tags":[],"updatedAt":"2024-11-02T07:08:55+00:00","versionOfRecord":{"articleIdentity":"rs-4355241","link":"https://doi.org/10.1038/s41371-024-00968-5","journal":{"identity":"journal-of-human-hypertension","isVorOnly":false,"title":"Journal of Human Hypertension"},"publishedOn":"2024-11-01 04:00:00","publishedOnDateReadable":"November 1st, 2024"},"versionCreatedAt":"2024-06-20 16:19:51","video":"","vorDoi":"10.1038/s41371-024-00968-5","vorDoiUrl":"https://doi.org/10.1038/s41371-024-00968-5","workflowStages":[]},"version":"v1","identity":"rs-4355241","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4355241","identity":"rs-4355241","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}