Use of multiple sclerosis disease-modifying therapies during pregnancy in France: Nationwide study between 2010 and 2021.

BACKGROUND: Multiple sclerosis (MS) frequently affects women of childbearing age and pregnant women. OBJECTIVE: To assess the use of MS disease-modifying therapies (DMTs) during pregnancy in France over the last decade, marked by an increasing DMTs availability. METHODS: All pregnancies ended from April 2010 to December 2021 in women with MS were identified based on the nationwide Mother-Child Register EPI-MERES, built from the French National Health Data System (Système National des Données de Santé (SNDS)). RESULTS: Of a total of 20,567 pregnancies in women with MS, 7587 were exposed to DMT. The number of DMT-exposed pregnancies markedly increased from 1079 in 2010-2012 to 2413 in 2019-2021 (+124%), especially those exposed to glatiramer acetate, natalizumab, dimethyl fumarate, and anti-CD20. Among pregnancies of women on DMT 6 months before pregnancy, 78.0% underwent DMT discontinuation and 7.6% switched DMT, generally before (33.0% and 77.0%, respectively) or during the first trimester of pregnancy (58.3% and 17.8%, respectively). DMT discontinuation decreased from 84.0% in 2010-2012 to 72.4% in 2019-2021 and was less frequent among women aged ⩾35 years and those socioeconomically disadvantaged. CONCLUSION: Despite MS therapeutic management adaptations to pregnancy, exposure during pregnancy to treatments whose safety profile has not yet been clearly established has increased sharply over the last decade.

Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.

Untreated patients with multiple sclerosis: A study of French expert centers.

BACKGROUND AND PURPOSE: Disease-modifying therapies (DMTs) have an impact on relapses and disease progression. Nonetheless, many patients with multiple sclerosis (MS) remain untreated. The objectives of the present study were to determine the proportion of untreated patients with MS followed in expert centers in France and to determine the predictive factors of nontreatment. METHODS: We conducted a retrospective cohort study. Data were extracted from the 38 centers participating in the European Database for Multiple Sclerosis (EDMUS) on December 15, 2018, and patients with MS seen at least once during the study period (from June 15, 2016 to June 14, 2017) were included. RESULTS: Of the 21,189 patients with MS (age 47.1 ± 13.1 years; Expanded Disability Status Scale (EDSS) score 3.4 ± 2.4), 6,631 (31.3%; 95% confidence interval [CI] 30.7-31.9) were not receiving any DMT. Although patients with a relapsing-remitting course (n = 11,693) were the most likely to receive DMT, 14.8% (95% CI 14.2-15.4) were still untreated (6.8% never treated). After multivariate analysis among patients with relapsing-remitting MS, the main factors explaining never having been treated were: not having ≥9 lesions on brain magnetic resonance imaging (odds ratio [OR] 0.52 [95% CI 0.44-0.61]) and lower EDSS score (OR 0.78 [95% CI 0.74-0.82]). Most patients with progressive MS (50.4% for secondary and 64.2% for primary progressive MS) did not receive any DMT during the study period, while 11.6% of patients with secondary and 34.0% of patients with primary progressive MS had never received any DMT. CONCLUSION: A significant proportion of patients with MS did not receive any DMT, even though such treatments are reimbursed by the healthcare system for French patients. This result highlights the unmet need for current DMTs for a large subgroup of patients with MS.

Social norms in patients with relapsing-remitting multiple sclerosis: Impairment of the moral/conventional distinction?

In multiple sclerosis, conflicting results have been reported between social impairment and relatively preserved moral judgments, mainly tested with moral dilemmas. Some results even yet suggest signs of "ultra-morality" in these patients. The objective of the present study was to test this hypothesis with the moral/conventional distinction task, investigating the knowledge of social norms and the judgment of moral versus conventional transgressions. In the first condition, the permissibility of social situations was estimated. If the participant judged the situation as wrong, he had to estimate the seriousness of the transgression, to give verbal justifications and to re-estimate the permissibility when the law authorizes the act (generalization condition) and when a social authority recommends the act (dependency condition). Forty-six multiple sclerosis patients matched to healthy controls completed this task. Contrary to our hypotheses, patients showed less permissibility for moral transgressions or a higher seriousness but, unexpectedly, for conventional transgressions. Most importantly, abnormal justifications were observed (strictly moral arguments for conventional transgressions and vice versa). This suggests a lack of distinction between conventional and moral judgment in multiple sclerosis. This confusion may explain the "ultra-morality" sometimes reported, if patients base their judgment mainly on social knowledge and not on emotional processing.

Impairments of humour comprehension in multiple sclerosis.

BACKGROUND: Sociocognition is an important field of neuropsychology involving human interactions. In relapsing-remitting multiple sclerosis, it was recently demonstrated that sociocognition is severely and precociously impaired. Among sociocognitive abilities, humour has not yet been considered in this disease despite its important social functions, including during doctor-patient communication. Its main functions are to reduce stress when interactions become strained and to convey difficult messages in a gentle form. Thus, the inability to perceive this second degree of language is likely to generate a major social handicap. As humour is a higher cognitive process, its assessment requires the control of lower levels according to a serial model. METHODS: The present humour comprehension protocol, based on a serial cognitive model, consisted of a first incongruity detection step (normality identification task) and a second incongruity resolution step (funniness identification task). This protocol was administered using both verbal and visual material (stories and cartoons). For each type of material, the participant had to decide which of three proposed endings was normal (normality identification) and which was funny (funniness identification). A group of 21 relapsing-remitting multiple sclerosis patients was compared to a control group of 38 healthy participants. In view of the severe impairment demonstrated for MS patients in other sociocognitive abilities, we predicted a deficit of humour comprehension in these patients in comparison with healthy participants. In reference to the serial model of humour, and considering the variability of MS lesions, our main goal was to test the hypothesis of a primary deficit in incongruity resolution (selective to funniness identification) in some MS patients whereas others may suffer a non-specific comprehension impairment (affecting both normality and funniness identification). RESULTS: Group analyses (non-parametric tests, Mann-Whitney) revealed lower scores for relapsing-remitting multiple sclerosis patients compared to controls for the visual tasks (normality and funniness). No significant difference was found in the verbal tasks. At the individual level, 62% of relapsing-remitting multiple sclerosis patients showed impairment compared to controls for the funniness tasks. Moreover, 38% presented a selective deficit in the funniness tasks. CONCLUSION: These preliminary results suggest that a high proportion of relapsing-remitting multiple sclerosis patients may be impaired in humour comprehension, some as a primary deficit and others as a secondary deficit to more general comprehension difficulties. On a theoretical level, the dissociations obtained between verbal and visual material do not support an amodal humour comprehension model.

Early Management of Transient Ischemic Attack in Emergency Departments in France.

INTRODUCTION: Emergency departments play a key role in the diagnosis and treatment of transient ischemic attacks, but limited data are available about the early management of such patients in emergency wards. Therefore, we aimed to evaluate emergency physicians' management of transient ischemic attack and analyze variations factors. METHODS: A multicenter survey among emergency physicians of the Grand Est region network (Est-RESCUE) was conducted from January 28th to March 28th, 2019. Medical and administrative data were collected by the same network and the national directory of medical resources. RESULTS: Among 542 emergency physicians recipients, 78 answered (14%) and 71 were finally included, practicing in 25 public hospitals homogeneously distributed across the territory, including 3 university hospitals. A cerebral magnetic resonance imaging was obtained for 75%-100% of patients by 4.3% of responders, 36.4% of which were performed within more than 24 hours. A cardiac monitoring was prescribed in 75%-100% of cases by 32.4% of responders. A neurologic consultation was routinely requested by 84.6% of responders practicing in a university hospital and 36.8% of responders practicing in a community hospital (P = .02). Patients were hospitalized in a neurovascular unit in 75%-100% of cases by 17.4% of responders, which happened more likely in university hospitals (P < .001). CONCLUSIONS: Transient ischemic attack suffers from management disparities across territories, due to limited access to technical facilities and neurologic consultations. Therefore, international recommendations are too often not followed. Implementation of territorial neurovascular tracks may help to standardize the management of these patients.

Glucose Modifies the Effect of Endovascular Thrombectomy in Patients With Acute Stroke.

Background and Purpose- Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods- Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0-6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results- Median (interquartile range) serum glucose on admission was 120 (104-140) mg/dL (6.6 mmol/L [5.7-7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69-2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or >90 mg/dL (5.0 mmol/L; P=0.019 for interaction; acOR, 3.81; 95% CI, 1.73-8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53-2.19 for patients >90 mg/dL), and glucose < or >100 mg/dL (5.5 mmol/L; P=0.004 for interaction; acOR, 3.17; 95% CI, 2.04-4.93 versus acOR, 1.72; 95% CI, 1.42-2.08) but not between subgroups above these levels of glucose. Conclusions- EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0-5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.

Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?

BACKGROUND AND PURPOSE: We aimed to identify the best definition of early neurological improvement (ENI) at 2 and 24 hours after mechanical thrombectomy (MT) and determine its ability to predict a good functional outcome at 3 months. METHODS: This retrospective analysis was based on a prospectively collected registry of patients treated by MT for ischemic stroke from May 2010 to March 2017. We included patients treated with stent-retrievers with National Institute of Health Stroke Scale (NIHSS) score before treatment and at 2 and/or 24 hours after treatment and modified Rankin Score (mRS) at 3 months. Receiver operating characteristic curve analysis was performed to estimate optimal thresholds for ENI at 2 and 24 hours. The relationship between optimal ENI definitions and good outcome at 3 months (mRS 0-2) was assessed by logistic regression. RESULTS: The analysis included 246 patients. At 2 hours, the optimal threshold to predict a good outcome at 3 months was improvementin the NIHSS score of >1 point (AUC 0.83,95% CI 0.77 to 0.87), with sensitivity and specificity 78.3% (62.2-85.7%) and 84.6% (77.2-90.3%), respectively, and OR 12.67 (95% CI 4.69 to 31.10, p<0.0001). At 24 hours, the optimal threshold was an improvementin the NIHSS score of >4 points (AUC 0.93, 95% CI 0.89 to 0.96), with sensitivity and specificity 93.8% (87.7-97.5%) and 83.2% (75.7-89.2%), respectively, and OR 391.32 (95% CI 44.43 to 3448.35, p<0.0001). CONCLUSIONS: ENI 24 hours after thrombectomy appears to be a straightforward surrogate of long-term endpoints and may have value in future research.

Mechanical Thrombectomy for Tandem Occlusions of the Internal Carotid Artery-Results of a Conservative Approach for the Extracranial Lesion.

Background: Mechanical thrombectomy (MT) is of clinical benefit for patients with extracranial-intracranial tandem lesions of anterior circulation. However, the optimal approach to the cervical lesion of the internal carotid artery (ICA) during MT has yet to be established. Data on a conservative approach for the proximal lesion during the acute phase are scarce. Methods: A retrospective study on an institutional, prospective database was conducted. We included patients with anterior circulation stroke presenting with a tandem lesion that was approached conservatively during MT. Results: Thirty-five 35 patients were included, of whom 25 (71.4%) had an atheromatous ICA lesion and 10 (28.6%) a dissection. Despite implementing a conservative strategy, acute percutaneous transluminal angioplasty (PTA) and/or stenting was necessary in 8 (22.9%) and 3 patients (8.6%), respectively. Of 27 surviving patients, 7 (25.9%) underwent delayed treatment of the ICA lesion. No new embolic events occurred between MT and delayed treatment. A favorable clinical outcome (mRS ≤ 2) was achieved in 15/35 patients (45.7%) and was associated with higher baseline ASPECTS (OR 1.62, 95% CI 1.08-2.45, p = 0.002) and successful recanalization (OR 9.39, 95% CI 1.92-45.80, p = 0.0005). Successful recanalization (TICI ≥ 2B) itself was observed in 54.3% of patients and was more likely with acute treatment of the proximal ICA lesion (OR 6.3, 95% CI 11-35.67, p = 0.03) and, more importantly, by the use of distal access catheters (OR 16.25, 95% CI 3.06-86.41, p = 0.0001). Conclusion: A conservative approach for ICA lesions during MT is feasible and offers favorable outcomes and successful recanalization for a significant proportion of patients. However, acute treatment of the cervical lesion is often necessary (31.4%) to make the distal occlusion accessible. Clinical outcome is influenced by the size of the baseline ischemic core and by successful recanalization; the latter is strongly favored by the use of distal access catheters to pass the proximal lesion. The fact that acute treatment of the ICA lesion favored intracranial recanalization but had no effect on clinical outcome is probably due to sample size, emphasizing the need for large scale, randomized studies to determine the optimal treatment strategy for this pathology.

Chapman-Cook' complex reading comprehension test: better performances for aged participants in comparison with youngers for level of schooling lower than baccalaureate.

We studied the comprehension abilities of healthy participants with a French version of the Chapman-Cook Speed of Reading Test. The objective was to assess the effect of gender, age and educational level on chronometric performances and errors. In this test, the task is to cross out an inappropriate word within short passages. In the original version, the participant is told to perform as quickly as possible during 150 seconds. The score is usually the number of passages correctly completed within this time limit. In the present study, we measured the time to achieve the first 10 passages, the first 14 passages corresponding to the first page and the total (29 passages) corresponding to the two pages. The number of errors was also considered. The normative sample included 150 participants (63 males; 87 females) with three educational level (47: superior to baccalaureate; 21: baccalaureate and 78: inferior to baccalaureate). Age was between 20 and 69 years old, divided in 5 age groups, without neurological or psychiatric disease, or cognitive abnormal development. All were French native speaking and have been schooling in France. For time completion, no effect of gender was found, but a significant and unexpected effect of age was shown according to educational level. Whereas the age groups obtained similar times for educational levels superior to baccalaureate, an age effect was demonstrated for the educational level inferior to baccalaureate. Participants over 40 years of age were faster than younger participants with the same educational level and similar than all age groups of higher educational level. On the contrary, young participants were slower compared to those with high educational levels and all older participants without baccalaureate. This surprising result is discussed.

Fronto-Subcortical Circuits for Cognition and Motivation: Dissociated Recovery in a Case of Loss of Psychic Self-Activation.

In humans and non-humans primates, extensive evidence supports the existence of subcortico-cortical circuits for cognition and behavior. Lesions studies are critical to understand the clinical significance of these functionally segregated circuits. Mapping these circuits from lesion studies is difficult given the heterogeneous etiology of the lesions, the lack of long-term and systematic testing of cognitive and behavioral disturbances, as well as the scarcity of neuroimaging data for identifying the precise location and extent of subcortical lesions. Here, we report the long-term follow-up study of a patient who developed a loss of psychic self-activation associated to a dysexecutive syndrome following resuscitation from cardiac arrest. Neuroimaging revealed extensive bilateral lesions in the putamen, with a relative spare of the caudate, and exhibiting a dorsoventral gradient that was predominantly rostrally to the anterior commissure and spared most of the ventral striatum. In comprehensive neuropsychological and neuropsychiatric assessments, we observed dissociation between the improvement of the self-activation deficits and the stability of the dysexecutive syndrome. The pattern of recovery after this lesion lends support to current models proposing the existence of two main subcortico-cortical circuits: a dorsal circuit, mostly mediating cognitive processes, and a ventral circuit, implicated in motivation.

Social Cognition Abilities in Patients With Different Multiple Sclerosis Subtypes.

OBJECTIVES: Multiple sclerosis (MS) can be associated with impaired social cognition. However, social cognition skills have never been explored in the different subtypes of MS. The first aim of this study was to examine whether MS subtypes differ on the course of social cognition. The second aim was to explore the relationship between social cognition performances and executive abilities and mood variables. METHODS: Sixty-two patients with MS and 33 healthy matched controls performed experimental tasks assessing facial emotion recognition, theory of mind (ToM), and cognitive functioning, in particular executive functions. RESULTS: Patients differed from controls on both measures of social cognition. On the ToM measures, patients with progressive MS scored significantly lower than healthy participants. Patients with primary progressive MS performed worse than both healthy participants and patients with relapsing-remitting MS on the recognition of fearful facial expressions, while patients with secondary progressive MS performed worse on the recognition of facial expressions of sadness. Patients' social cognition difficulties were correlated with processing speed, working memory, and verbal fluency. CONCLUSIONS: These preliminary results suggested that there may be qualitative differences in social cognition difficulties among the phenotypes. Furthermore, these impairments were related to executive functions, but unrelated to patients' disability or level of depression. These data highlight the need for research to determine the real impact of these deficits on interpersonal relationships among patients and to confirm these disorders in a larger population with progressive forms of MS. (JINS, 2017, 23, 653-664).

When synesthesia and savant abilities are mistaken for hallucinations and delusions: contribution of a cognitive approach for their differential diagnosis.

OBJECTIVE: Schizophrenia is characterized by hallucinations, delusions, disorganized speech and behavior, and other symptoms that cause social or occupational dysfunction. However, some of these symptoms, such as hallucinations and delusions, can be indicative of other phenomena such as synesthesia and savant abilities. The aim of this paper is to highlight how neurological and psychiatric conditions can be confused and how formal neuropsychological evaluations can be necessary to distinguish them. METHOD: We report the case of a young woman, VA, who perceived sounds as colors and claimed to have elaborated complex astrophysical reasoning, despite having experienced difficulties at school, especially in mathematics. VA also had difficulties to orient herself, to develop social relationships, and often became confused by daily life situations. These elements were considered as symptoms of schizophrenia. RESULTS: Evaluations revealed that VA exhibited savant abilities in astrophysics and colored-hearing synesthesia. We also found evidence of higher-than-average cognitive functioning. CONCLUSIONS: In complex cases, neuropsychological and formal evaluations are necessary to establish a differential diagnosis. Moreover, the case highlights the link between synesthesia and savant abilities.

Characteristics of Alzheimer's Disease Patients with Severe Executive Disorders.

BACKGROUND: Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations. OBJECTIVE: The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction. METHODS: The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery. RESULTS: 381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as ≥2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months. CONCLUSIONS: Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes.

Cross-validation of a Shortened Battery for the Assessment of Dysexecutive Disorders in Alzheimer Disease.

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

Systemic Sarcoidosis Mimicking a Behavioural Variant of Frontotemporal Dementia.

Among rare neurological manifestations, a progressive dementia may exceptionally be the revealing clinical feature of a sarcoidosis. Diagnosis may then be difficult, especially when systemic signs are missing or latent, with a risk of therapeutic delay. We report the first case of sarcoidosis mimicking a frontotemporal dementia. A 53-year-old man presented with a dementia clinically suggestive of frontotemporal dementia, progressing slowly for about 2 years. However, MRI revealed unusual aspects, mainly large areas of T2/FLAIR hypersignal within temporal regions and cerebellum, with nodular leptomeningeal and juxtacortical Gadolinium enhancement. The patient was finally diagnosed with a systemic sarcoidosis. We discuss the differential diagnosis based on MRI aspects and review the literature on the clinical, biological, and imaging features of sarcoidosis presenting with dementia. This case demonstrates that brain imaging remains mandatory in the exploration process of a patient with dementia. Although the patient presented with rather typical features of a behavioural variant of frontotemporal dementia, the MRI aspect was the key exploration that leaded to the diagnosis.

Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-ß1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-ß1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD.