[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

[Subacute cerebellar ataxia, an uncommon SARS-CoV-2 complication infection in older adults]. / Ataxie cérébelleuse subaiguë : une atteinte atypique par le SARS-CoV-2 chez la personne âgée.

Cerebellar ataxia can be caused by neoplasia, toxics (drugs, heavy metals, alcohol), infection, vascular lesions or auto-immune and paraneoplastic pathologies. Neuroimaging must be performed urgently in case of sudden onset and serologies as well as a lumbar puncture should be performed. Several case reports of ataxia associated with COVID-19 have been published, however the underlying pathogenic mechanisms remain unclear. This is a diagnosis of exclusion when other causes are ruled out and when the ataxia appears simultaneously to COVID-19 infection. We lack data on best management, but the prognosis appears mostly favorable with good functional recovery without any specific treatment. This paper describes the case of a patient who developed a cerebellar ataxia as the only neurological manifestation of a SARS-CoV-2 infection.

Une ataxie cérébelleuse peut être causée par un processus (para)néoplasique, auto-imun, une exposition toxique, une infection ou une lésion vasculaire. Une imagerie doit être réalisée en urgence devant toute atteinte aiguë et le bilan devrait être complété par des sérologies larges et une ponction lombaire. Plusieurs cas d'ataxie liée au Covid-19 ont été décrits, dont le mécanisme étiopathogénique reste incomplètement élucidé, le diagnostic se faisant plutôt par exclusion lorsque les symptômes apparaissent de manière concomitante à l'infection. Des données manquent sur la prise en charge mais le pronostic semble favorable, avec une bonne récupération fonctionnelle. Cet article décrit le cas d'une patiente ayant présenté une ataxie cérébelleuse comme symptôme neurologique isolé contemporain d'une infection à SARS-CoV-2.

[Neurology : what's new in 2021]. / Neurologie.

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache.

L'année 2021 a été marquée par la publication des nouveaux critères diagnostiques, classifications et guidelines (polyradiculonévrite inflammatoire démyélinisante chronique, tumeurs cérébrales, encéphalites autoimmunes). L'attitude thérapeutique dans les épilepsies focales ou généralisées et l'épilepsie chez la femme enceinte a été mieux définie. Les marqueurs biologiques et les immunothérapies modifient le paysage de la prise en charge des démences. Le traitement endovasculaire des AVC de la circulation antérieure semble efficace indépendamment d'une thrombolyse préalable, ainsi qu'en cas d'AVC sévère de la circulation postérieure. Les complications neurologiques du SARS-CoV-2 ont été éclaircies et l'efficacité des vaccins étudiée chez les patients immunosupprimés. Plusieurs nouvelles molécules et techniques montrent des résultats prometteurs pour les migraines et céphalées en grappe.

[Cancer-related cognitive impairment in older adults]. / Troubles neurocognitifs chez les personnes âgées avec maladie oncologique.

Chemotherapy is associated with transient or permanent cognitive dysfunction ranging from subjective complaints to measurable deficits in working memory, attention and language. Given that old age may be related to cognitive decline, the interaction between chemotherapy-induced cognitive impairment and the effects of age is of growing concern in view of our aging population. Chemotherapy-associated cognitive dysfunction may have an additive impact on pre-existing age-related cognitive performance decline, which calls for awareness in its detection, to reduce impact on quality of life and improve management of older patients. We discuss here the « chemobrain ¼, concept, review the existing evidence about pathophysiology, neuroimaging and cognitive phenotype and propose practical tools for routine detection in the outpatient setting.

Les chimiothérapies peuvent induire une dysfonction cognitive transitoire ou permanente, pouvant aller d'une plainte cognitive subjective à une atteinte réelle de la mémoire de travail, de l'attention ou du langage. L'interaction entre l'atteinte cognitive attribuée à ces thérapies et celle liée à l'âge est une question grandissante compte tenu du vieillissement de la population. Elle justifie une attention particulière à la détection précoce de troubles cognitifs afin d'en réduire l'impact négatif sur la qualité de vie et optimiser la prise en charge médicale. Dans cet article, nous abordons le concept de « chemobrain ¼, et en revoyons les connaissances actuelles de physiopathologie, de neuro-imagerie ainsi que les phénotypes neuropsychologiques, afin de proposer quelques outils de détection et de prise en charge au cabinet.

Combined microwave processing and enzymatic proteolysis of bovine whey proteins: the impact on bovine ß-lactoglobulin allergenicity.

The main aim of this study was to develop a continuous microwave treatment system of whey proteins and then apply this process at 37 °C, 50 °C, 65 °C and 70 °C to achieve pepsinolysis and produce extensively hydrolysed bovine whey protein hydrolysates with low allergenic properties. The microwave process was compared to a conventional thermal treatment with similar temperature set points. Both processes were deeply analysed in terms of the thermal kinetics and operating conditions. The pepsin hydrolysates obtained by the continuous microwave treatment and conventional heating were characterized by SDS-PAGE and RP-HPLC. The allergenicity of the whey protein hydrolysates was explored using a human IgE sensitized rat basophil leukaemia cell assay. The results indicate that extensively hydrolysed whey protein hydrolysates were obtained by microwave only at 65 °C and in a shorter time compared with the conventional thermal treatment. In the same temperature conditions under conventional heating, ß-lactoglobulin was resistant to pepsinolysis, and 37% of it remained intact. As demonstrated by an in vitro degranulation assay using specific human IgE-sensitized rat basophils, the extensively hydrolysed whey protein obtained by microwave showed maximum degranulation values of 6.53% compared to those of the native whey protein isolate (45.97%) and hence elicited no more allergenic reactions in basophils. This work emphasizes the potential industrial use of microwave heating specific to milk protein processing to reduce their allergenicity and improve their end-use properties.

[Neurology]. / Neurologie.

Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised. Generic use of lamotrigine does not result in recrudescence of epileptic seizures or adverse effects.

L'ocrélizumab (Ocrevus), un anticorps monoclonal anti-CD20, a été homologué dans le traitement de la sclérose en plaques. L'éculizumab (Soliris) a été approuvé dans plusieurs pays pour les formes réfractaires de myasthénie grave généralisée séropositive. Une forme de thérapie génique, le patisiran a montré des résultats positifs dans l'amyloïdose à transthyrétine. Dans le traitement des céphalées, en particulier des migraines, les approches non pharmacologiques ont montré quelques avancées. Les critères de la démence à corps de Lewy ont été révisés. L'utilisation de génériques de la lamotrigine n'engendre pas de recrudescence de crises épileptiques ni d'effets indésirables.

Plasma ß-amyloid 40 levels are positively associated with mortality risks in the elderly.

BACKGROUND: We evaluated if plasma ß-amyloid (Aß) levels were associated with mortality risks in a subsample of the French Three-City (3C) prospective cohort study. METHODS: Analyses were based on 1254 participants randomly selected from the initial 3C cohort stratified by center, sex, and age in the context of a nested case-cohort study to investigate biological variables. Associations between plasma Aß and mortality were assessed with the Cox regression model with delayed entry including various potential confounding factors and testing possible mediators. RESULTS: A relationship between high plasma Aß1-40 concentrations and risk of mortality (hazards ratio, 1.15; 95% confidence interval, 1.01-1.31, P = .03) was unveiled independently of age, educational level, vascular risk factors, diet, physical activity, cognitive impairment, or frailty status. It was only modified when we included cystatin C levels. CONCLUSIONS: Further investigations are needed to determine precisely the pathophysiological roles of plasma Aß1-40 and cystatin C and before envisioning any future clinical applications.

Factors associated with early recurrence at the first evaluation of patients with transient ischemic attack.

We aimed to identify factors easily collected at admission in patients with transient ischemic attack (TIA) that were associated with early recurrence, so as to guide clinicians' decision-making about hospitalization in routine practice. From September 2011 to January 2013, all TIA patients who were referred to the University Hospital of Dijon, France, were identified. Vascular risk factors and clinical information were collected. The etiology of the TIA was defined according to the results of complementary examinations performed at admission as follows: large artery atherosclerosis (LAA-TIA) TIA, TIA due to atrial fibrillation (AF-TIA), other causes, and undetermined TIA. Logistic regression analyses were performed to identify factors associated with any recurrence at 48 hours (stroke or TIA). Among the 312 TIA patients, the etiology was LAA-TIA in 33 patients (10.6%), AF-TIA in 57 (18.3%), other causes in 23 (7.3%), and undetermined in 199 (63.8%). Early recurrence rates were 12.1% in patients with LAA-TIA, 5.3% in patients with AF-TIA, 4.3% in patients with another cause of TIA, and 1.0% in patients with undetermined TIA. In multivariable analysis, the LAA etiology was independently associated with early recurrence (odds ratio [OR]: 12.03; 95% confidence interval [CI]: 1.84-78.48, p=0.009). A non-significant trend was also observed for AF-TIA (OR: 3.82; 95% CI: 0.40-36.62, p=0.25) and other causes (OR: 3.73; 95% CI: 0.30-46.26, p=0.31). A simple initial assessment of TIA patients in the emergency room would be helpful in targeting those with a high risk of early recurrence and who therefore need to be hospitalized.

A de novo nonsense PDGFB mutation causing idiopathic basal ganglia calcification with laryngeal dystonia.

Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurologic and psychiatric symptoms. In families with autosomal dominant inheritance, three causative genes have been identified: SLC20A2, PDGFRB, and, very recently, PDGFB. Whereas in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrence are rare. We report the case of a 20-year-old woman who presented laryngeal dystonia revealing IBGC. Her healthy parents' CT scans were both normal. We identified in the proband a new nonsense mutation in exon 4 of PDGFB, c.439C>T (p.Gln147*), which was absent from the parents' DNA. This mutation may result in a loss-of-function of PDGF-B, which has been shown to cause IBGC in humans and to disrupt the blood-brain barrier in mice, resulting in brain calcification. The c.439C>T mutation is located between two previously reported nonsense mutations, c.433C>T (p.Gln145*) and c.445C>T (p.Arg149*), on a region that could be a hot spot for de novo mutations. We present the first full demonstration of the de novo occurrence of an IBGC-causative mutation in a sporadic case.

High plasma estradiol interacts with diabetes on risk of dementia in older postmenopausal women.

OBJECTIVE: We aimed to investigate the impact of endogenous estradiol (E2) on dementia and to evaluate the contribution of vascular risk factors and inflammatory and blood coagulation markers to this association. METHODS: Using data from a French population-based prospective study (the Three-City Study) including 5,644 postmenopausal women aged 65 years or older, we investigated the association of endogenous total-E2 and bioavailable-E2 and total-testosterone with the 4-year incidence of all-cause dementia. We further focused on the role of dementia and cardiovascular risk factors as well as inflammation (C-reactive protein, fibrinogen) and hypercoagulability (fibrin d-dimers, thrombin generation) in these associations. We used a case-cohort design consisting of a random subcohort of 562 women not using hormone therapy and 132 incident dementia cases. RESULTS: Adjusted Cox proportional hazards models showed a J-shaped relationship between total-E2 and risk of dementia (p = 0.001). Total-E2 values in the lower and upper quartiles were associated with an increased dementia risk (adjusted hazard ratio [HR] [95% confidence interval] = 2.2 [1.1-4.5] and HR = 2.4 [1.2-5.2], respectively). Importantly, the risk associated with higher E2 levels was dramatically increased in women with diabetes compared with nondiabetic women (adjusted HR associated with the upper E2 quartile = 14.2 [1.60-123] and HR = 3.4 [0.1-147], respectively, p interaction <0.05). Similar results were found for bioavailable-E2. Adjustment for inflammatory and blood coagulation markers did not modify our results. No significant association was found for total-testosterone. CONCLUSION: High E2 level is an independent predictor of incident dementia, particularly in postmenopausal women with diabetes.

Estrogen receptor polymorphisms and incident dementia: the prospective 3C study.

BACKGROUND: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. METHODS: The association between five ESR α (ESR1) and ß (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. RESULTS: Among women, the CC genotype of ESR1rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03-2.28, P = .03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81-5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37-2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P = .04). Hormone treatment did not modify these associations, and there were no significant associations in men. CONCLUSIONS: Although there was only weak support for a gender-specific association between the common ESR1rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.

Trends in the incidence of ischaemic stroke in young adults between 1985 and 2011: the Dijon Stroke Registry.

BACKGROUND: Recent data have suggested that stroke incidence in young people may be rising. In this population-based study, we aimed to determine whether the incidence of stroke in people aged <55 years old had changed over the last three decades. METHODS: All cases of first-ever stroke (ischaemic stroke, spontaneous intracerebral haemorrhage, and undetermined stroke) occurring in Dijon, France, from 1985 to 2011 were prospectively collected from a population-based registry. Incidence rates were calculated and temporal trends were analysed by age groups and stroke subtypes using a Poisson regression to estimate incidence rate ratios (IRR). Risk factors and premorbid treatments were analysed. RESULTS: Over the 27-year study period, 4506 patients were recorded (53% women, mean age 74.6±14.4, 10.1% aged <55 years). An increase in overall stroke incidence was noted, as was a rise in ischaemic stroke in individuals aged <55 years (IRR 1.308; 95% CI 0.982 to 1.741, p=0.066 for period 1994-2002 vs period 1985-1993, and IRR 1.697; 95% CI 1.340 to 2.150, p<0.001 for period 2003-2011 vs period 1994-2002), which was consistent for men and women. In these young patients, smoking was the most frequent risk factor (43%). CONCLUSIONS: Multiple factors may account for the increased incidence of ischaemic stroke in people aged <55 years including changes in vascular risk factors, better awareness of the disease and treatment options in the population and among practitioners leading to more frequent referrals for specialised care, and improvements in stroke diagnosis. Stroke prevention must be encouraged even in young adults.

Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification.

Idiopathic basal ganglia calcification is characterized by mineral deposits in the brain, an autosomal dominant pattern of inheritance in most cases and genetic heterogeneity. The first causal genes, SLC20A2 and PDGFRB, have recently been reported. Diagnosing idiopathic basal ganglia calcification necessitates the exclusion of other causes, including calcification related to normal ageing, for which no normative data exist. Our objectives were to diagnose accurately and then describe the clinical and radiological characteristics of idiopathic basal ganglia calcification. First, calcifications were evaluated using a visual rating scale on the computerized tomography scans of 600 consecutively hospitalized unselected controls. We determined an age-specific threshold in these control computerized tomography scans as the value of the 99th percentile of the total calcification score within three age categories: <40, 40-60, and >60 years. To study the phenotype of the disease, patients with basal ganglia calcification were recruited from several medical centres. Calcifications that rated below the age-specific threshold using the same scale were excluded, as were patients with differential diagnoses of idiopathic basal ganglia calcification, after an extensive aetiological assessment. Sanger sequencing of SLC20A2 and PDGFRB was performed. In total, 72 patients were diagnosed with idiopathic basal ganglia calcification, 25 of whom bore a mutation in either SLC20A2 (two families, four sporadic cases) or PDGFRB (one family, two sporadic cases). Five mutations were novel. Seventy-one per cent of the patients with idiopathic basal ganglia calcification were symptomatic (mean age of clinical onset: 39 ± 20 years; mean age at last evaluation: 55 ± 19 years). Among them, the most frequent signs were: cognitive impairment (58.8%), psychiatric symptoms (56.9%) and movement disorders (54.9%). Few clinical differences appeared between SLC20A2 and PDGFRB mutation carriers. Radiological analysis revealed that the total calcification scores correlated positively with age in controls and patients, but increased more rapidly with age in patients. The expected total calcification score was greater in SLC20A2 than PDGFRB mutation carriers, beyond the effect of the age alone. No patient with a PDGFRB mutation exhibited a cortical or a vermis calcification. The total calcification score was more severe in symptomatic versus asymptomatic individuals. We provide the first phenotypical description of a case series of patients with idiopathic basal ganglia calcification since the identification of the first causative genes. Clinical and radiological diversity is confirmed, whatever the genetic status. Quantification of calcification is correlated with the symptomatic status, but the location and the severity of the calcifications don't reflect the whole clinical diversity. Other biomarkers may be helpful in better predicting clinical expression.

Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women.

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.

Endogenous oestradiol as a positive correlate of plasma fibrinogen among older postmenopausal women: a population-based study (the Three-City cohort study).

BACKGROUND: Plasma fibrinogen is a strong predictor of ischaemic arterial disease in women. Sex steroid hormones including hormone therapy may play an important role in the development of cardiovascular disease. However, whether endogenous sex steroid hormones influence the plasma fibrinogen concentrations among postmenopausal women remains unclear. OBJECTIVES: To investigate the association of plasma fibrinogen levels with endogenous sex steroid hormones and sex hormone binding globulin (SHBG) among postmenopausal women. METHODS: We used data from the French prospective Three-City cohort study that included 9294 noninstitutionalized men and women over 65 years of age. Total 17ß-oestradiol (E2, pg/ml), total testosterone (T, ng/ml), SHBG (nm) and fibrinogen (g/l) were measured in stored plasmas in a subcohort of 602 randomly selected postmenopausal women who used neither hormone medication nor anticoagulation therapy. Multivariate linear regression models were used to estimate the regression coefficients assessed in fibrinogen unit by 1 SD increase in log-distribution of sex steroid hormones and SHBG. RESULTS: E2 but neither T nor SHBG was positively associated with plasma fibrinogen levels (ß = 0·148, P < 0·001). Adjustment for cardiovascular risk factors including diabetes made no substantial change to the results (ß = 0·145, P < 0·001). The association of fibrinogen with E2 was stronger among women with body mass index over 25 kg/m(2) compared with those with normal weight (ß = 0·156, P < 0·001 and ß = 0·092, P = 0·02, respectively, P for interaction = 0·04). CONCLUSION: E2 emerges as a positive and independent correlate of plasma fibrinogen among postmenopausal women, especially in subjects who are overweight. These findings suggest a deleterious effect of endogenous oestrogens on cardiovascular risk profile among postmenopausal women.

Estrogen receptor alpha gene variants and major depressive episodes.

BACKGROUND: Despite evidence of estrogen's mood-enhancing effects, the association between estrogen receptor (ER) gene variants and lifetime major depression has been insufficiently studied. METHODS: 3987 community-dwelling women aged 65years and over were recruited in France as part of the Three City Study. Current and past major depressive disorders (MDD) were diagnosed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. The association between two common estrogen receptor alpha (ESR1) polymorphisms with lifetime MDD was examined using adjusted logistic regression models, taking into account the age at first depressive episode and the recurrence of depression. RESULTS: Women homozygous for the variant G allele of ESR1 rs9340799 had a 1.6-fold increased risk of MDD across their lifetime compared with women who were homozygous for the A allele (p=0.009). There was a similar non-significant trend for the C allele of rs2234693 being associated with an increased risk (p=0.09). Polytomous regression analysis further indicated that the GG genotype of rs9340799 was specifically associated with an increased risk of recurrent depressive episodes, regardless of the age at first onset of depression relative to the menopause. LIMITATIONS: The duration and severity of depressive episodes was not considered in the analysis. CONCLUSIONS: This is the first study to examine the association between ESR1 gene variants and lifetime MDD. Our findings indicate a significant association between common variants and the risk of recurrent depressive episodes. This suggests that certain depressed women could be most responsive to hormone-based treatment.

[Epidemiology of stroke in the elderly : "the silver tsunami"]. / Epidémiologie des accidents vasculaires cérébraux du sujet âgé : "The silver tsunami".

Stroke in the elderly has more major differences compared to young people. The first cause remains the atherothrombosis disease associated to the following risk factors: hypertension, diabetes, hypercholesterolemia, tobacco consumption. Lipohyalinosis of perforating arteries linked to blood hypertension inducing lacunar infarcts and atrial fibrillation are the 2nd and 3rd causes linked to age. The increase of the ageing population explains the rise of the number of stroke over 80 years. On a clinical point of view, the pseudo-bulbar syndrome is very frequent and explains the swallowing troubles and incontinence. Prognosis is characterized by a high risk of dementia (20 %). Primary and secondary prevention is very effective even in very old patients, on the risk of stroke. Fibrinolysis and stroke units have demonstrated their efficacy in stroke treatments over 80 years. We observed a decrease of case-fatality rates at any day with a delay in age of onset of stroke of 5 years in men and 8 years in women, suggesting an increase of life expectancy without stroke, reflecting a certain efficacy of prevention. The elderly may be more often included in therapeutic trials.

Oestrogen receptor polymorphisms and late-life depression.

BACKGROUND: Evidence suggests a role for oestrogen in depression but the involvement of oestrogen receptor polymorphisms remains unknown. AIMS: To determine the association between oestrogen receptor polymorphisms and late-life depression and the modifying effect of hormone treatment. METHOD: Depression was assessed using the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria and the Centre for Epidemiologic Studies - Depression Scale. The association between oestrogen receptor α and ß (ER-α and ER-ß) polymorphisms with severe depression was examined in 6017 community-dwelling elderly people using multivariate logistic regression. RESULTS: In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-ß rs1256049 increased the risk of depression, but only for non-current users of hormone treatment. In men, only the ER-ß rs4986938 polymorphism showed a weak association with depression risk. CONCLUSIONS: Oestrogen receptor polymorphisms are associated with severe late-life depression risk in women only.

Stroke in the very old: incidence, risk factors, clinical features, outcomes and access to resources--a 22-year population-based study.

BACKGROUND: For several years, the burden of stroke in very old patients has been increasing in western countries. Nevertheless, we have little information about this new challenge in individuals >or=80. METHODS: We ascertained all first-ever strokes in the population of Dijon, France (150,000 inhabitants), from 1985 to 2006. The incidence of stroke, risk factors, clinical presentation, resource mobilization and 1-month outcome were evaluated in individuals >or=80 and compared to the data obtained in younger patients. RESULTS: We collected 1,410 first-ever strokes in people >or=80 years (39%) versus 2,130 in those <80 years. The incidence was 997/100,000, and 68/100,000, respectively. Over the 22 years, the incidence of stroke in individuals >or=80 years rose significantly. A lower prevalence of diabetes, hypercholesterolemia and alcohol intake, as well as a higher prevalence of hypertension, atrial fibrillation, previous myocardial infarction and use of prestroke antiplatelet agents were noted in patients >or=80 years. The clinical presentation was severer and the 1-month outcome in terms of case fatality and handicap was worse, despite improvements observed over time. Finally, in patients >or=80 years, the use of CT scan, MRI, cervical Doppler, angiography and carotid surgery were significantly lower than for younger patients. Length of stay >30 days was more frequent, and discharge to prestroke residence was less common. However, all these improved between the first and the last study periods. CONCLUSIONS: Our findings have important implications not only for clinical management but also for initiating preventive strategies and health policy.

[Trends in stroke incidence and case-fatality rates over a 20-year period (1985-2004) in Dijon, France]. / Evolution sur vingt ans des taux d'incidence et de mortalité des AVC au sein de la population de dijon intra-muros: 1985-2004.

With progress in stroke prevention it is important to evaluate epidemiological trends over a long period and in an unselected population. We estimated changes in stroke incidence, the case-fatality rate, risk factors, and the use of primary prevention, based on a continuous registry of a well-defined population, from 1985 to 2004. We recorded 3142 ischemic strokes, 341 primary cerebral hemorrhages and 74 subarachnoid hemorrhages. During the 20-year study period, age at first stroke increased by 5 years in men and 8 years in women. Comparing the periods 1985-1989 and 2000-2004, the age - and sex-adjusted incidence rates of first-ever strokes were stable, except for lacunar strokes, the incidence of which increased significantly (p = 0.05), and also cardio-embolic stroke, the incidence of which fell significantly (p = 0.01). Twenty-eight-day case-fatality rates fell significantly, especially for lacunar stroke (p = 0.05) and primary cerebral hemorrhage (p = 0.03). The frequency of hypercholesterolemia and diabetes increased significantly (p < 0.01). In contrast, the frequency of myocardial infarction fell significantly (p = 0.02). The frequency of smoking and diastolic blood pressure J 90 mmHg also fell, but the difference was not significant because of missing data. The frequency of pre-stroke antiplatelet and anticoagulant treatment increased significantly (p < 0.01). The age - and sex-adjusted incidence rates of stroke in Dijon, France, have thus been stable for the past 20 years. Age at stroke onset has increased, the case-fatality rate has fallen, antiplatelet treatment is more frequent, and the frequency of some pre-stroke risk factors has fallen.