ABSTRACT
BACKGROUND: The need for early diagnosis biomarkers in Alzheimer's disease (AD) is growing. Only few studies have reported gustatory dysfunctions in AD using subjective taste tests. OBJECTIVE: The main purpose of the study was to explore gustatory functions using subjective taste tests and recordings of gustatory evoked potentials (GEPs) for sucrose solution in patients with minor or major cognitive impairment (CI) linked to AD, and to compare them with healthy controls. The secondary objective was to evaluate the relationships between GEPs and the results of cognitive assessments and fasting blood samples. METHODS: A total of 45 subjects (15 healthy subjects, 15 minor CI patients, 15 major CI patients) were included to compare their gustatory functions and brain activity by recording GEPs in response to a sucrose stimulation. CI groups were combined in second analyses in order to keep a high power in the study. Correlations were made with cognitive scores and hormone levels (ghrelin, leptin, insulin, serotonin). RESULTS: Increased P1 latencies and reduced N1 amplitudes were observed in minor or major patients compared to controls. GEPs were undetectable in 6 major and 4 minor CI patients. Thresholds for sucrose detection were significantly higher in the major CI group than in controls or the minor CI group. No correlation was found with hormone levels. CONCLUSIONS: The cortical processing of sensory taste information seems to be altered in patients with minor or major CI linked to AD. This disturbance was identifiable with subjective taste tests only later, at the major CI stage.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Taste Perception/physiology , Alzheimer Disease/complications , Evoked Potentials , Cognitive Dysfunction/complications , Sucrose , HormonesABSTRACT
OBJECTIVE: Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes. METHODS: After the identification of a deletion upstream of SLC20A2, we assessed its consequences on gene function by reverse transcriptase droplet digital polymerase chain reaction (RT-ddPCR), an ex vivo inorganic phosphate uptake assay, and introduced the deletion of a putative SLC20A2 enhancer mapping to this region in human embryonic kidney 293 (HEK293) cells by clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9). RESULTS: The 8p11.21 deletion, segregating with PFBC in a family, mapped 35 kb upstream of SLC20A2. The deletion carriers/normal controls ratio of relative SLC20A2 mRNA levels was 60.2% (P < 0.001). This was comparable with that of patients carrying an SLC20A2 premature stop codon (63.4%; P < 0.001). The proband exhibited a 39.3% decrease of inorganic phosphate uptake in blood (P = 0.015). In HEK293 cells, we observed a 39.8% decrease in relative SLC20A2 mRNA levels after normalization on DNA copy number (P < 0.001). DISCUSSION: We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss-of-function alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3-step strategy to identify and easily assess the effect of such events. © 2020 International Parkinson and Movement Disorder Society.
Subject(s)
Brain Diseases , Sodium-Phosphate Cotransporter Proteins, Type III , Brain/metabolism , DNA Copy Number Variations , HEK293 Cells , Haploinsufficiency/genetics , Humans , Mutation/genetics , Sodium-Phosphate Cotransporter Proteins, Type III/geneticsABSTRACT
BACKGROUND AND PURPOSE: Because of several methodological limitations, previous studies focusing on the prevalence of large vessel occlusion in ischemic stroke (IS) patients provided conflicting results. We evaluated the incidence of IS with a visible arterial occlusion using a comprehensive population-based registry. METHODS: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Annual incidence rates of IS (first-ever and recurrent events) and IS with a visible occlusion were calculated. RESULTS: One thousand sixty cases of IS were recorded (mean age: 76.0±15.8 years, 53.9% women). Information about arterial imaging was available in 971 (91.6%) of them, and only preexisting dementia was independently associated with having missing information (odds ratio=0.34 [95% CI, 0.18-0.65], P=0.001). Among these patients, 284 (29.2%) had a visible arterial occlusion. Occlusion site was the anterior circulation in 226 patients (23.3% of overall patients with available data) and the posterior circulation in 58 patients (6.0%). A proximal occlusion of the anterior circulation was observed in 167 patients (17.2%). The crude annual incidence rate of total IS per 100 000 was 138 (95% CI, 129-146). Corresponding standardized rates were 66 (95% CI, 50-82) to the World Health Organization and 141 (95% CI, 118-164) to the 2013 European populations. The crude annual incidence rate of IS with a visible arterial occlusion per 100 000 was 37 (95% CI, 33-41) and that of IS with a proximal occlusion of the anterior circulation was 22 (95% CI, 18-25). Corresponding standardized rates were 18 (95% CI, 10-26) and 10 (95% CI, 8-13) to the World Health Organization population, and 38 (95% CI, 26-50) and 23 (95% CI, 19-26) to the 2013 European population, respectively. CONCLUSIONS: These results will be helpful to plan the need for thrombectomy-capable stroke center resources.
Subject(s)
Arterial Occlusive Diseases/epidemiology , Stroke/epidemiology , Aged , Aged, 80 and over , Arterial Occlusive Diseases/complications , Brain Ischemia/epidemiology , Brain Ischemia/etiology , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Registries , Stroke/etiologyABSTRACT
OBJECTIVE: We assessed the association between pre-stroke cognitive status and 90-day case-fatality. METHODS: Patients with ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH) were prospectively identified among residents of Dijon, France, between 2013 and 2015, using a population-based registry. Association between pre-stroke cognitive status and case-fatality at 90 days was evaluated using Cox regression. RESULTS: Seven hundred sixty-two patients were identified, and information about pre-stroke cognitive status was obtained for 716 (92.6%) of them, including 603 IS (84.2%) and 113 ICH (15.8%). Before stroke, 99 (13.8%) patients had mild cognitive impairment (MCI) and 98 (13.7%) had dementia. Patients with cognitive impairment were older, had a higher prevalence of several risk factors, more severe stroke, more frequent ICH, and less admission to stroke unit. Case-fatality rate at 90 days was 11.7% in patients without cognitive impairment, 32.3% in MCI patients, and 55.1% in patients with dementia. In multivariable analyses, pre-existing MCI (hazard ratio [HR] 2.22, 95% CI 1.21-4.05, p = 0.009) and dementia (HR 4.35, 95% CI 2.49-7.61, p < 0.001) were both associated with 90-day case-fatality. CONCLUSION: Pre-stroke MCI and dementia were both associated with increased mortality. These associations were not fully explained by baseline characteristics, pre-stroke dependency, stroke severity or patient management, and underlying reasons need to be investigated.
Subject(s)
Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Registries/statistics & numerical data , Stroke/mortality , Aged , Aged, 80 and over , Comorbidity , Female , France/epidemiology , Humans , Male , Prospective Studies , Risk FactorsABSTRACT
Background: Fatigue is a frequent symptom after stroke. We aimed to determine the association between fatigue and cognitive performance in patients with ischemic stroke who received acute revascularization therapy (IV thrombolysis and/or mechanical thrombectomy). Methods: Seventy patients were prospectively included in the stroke unit of the University Hospital of Dijon, France. A follow-up was performed at 6 months with clinical examination, fatigue assessment by the Fatigue Severity Scale (FSS), and a comprehensive neuropsychological evaluation. Patients with fatigue (FSS score >4) were compared with patients without fatigue. Neuropsychological factors associated with fatigue at 6 months were analyzed using multivariable logistic regression models. Results: Fatigue was reported by 34.3% of patients. Patients with fatigue were older, had more frequent residual handicap, depressive symptoms, and impaired quality of life. They had more frequently low score (<26) on the MoCA scale (79.2 vs. 47.8%, OR = 4.15; 95% CI: 1.32-13, p = 0.015), memory impairment (60 vs. 30.6%, OR = 3.41; 95% CI: 1.09-10.7, p = 0.035), and executive dysfunction (65 vs. 30.8%, OR = 4.18; 95% CI: 1.33-13.1, p = 0.014). In multivariable logistic regression analysis, only memory impairment was independently associated with fatigue (OR = 5.70; 95% CI: 1.09-29.6, p = 0.039). Further analyses restricted to non-depressed patients (n = 58, 84.1%) showed in multivariable models that a score < 26 on MoCA scale (OR 5.12; 95% CI: 1.00-26.2, p = 0.05), and a memory impairment (OR = 6.17; 95% CI: 1.06-35.9, p = 0.043) were associated with fatigue. There was also a non-significant trend toward an association between divided attention deficit and fatigue (OR = 6.79; 95% CI: 0.80-57.6, p = 0.079). Conclusion: The association between fatigue and subtle cognitive impairment including memory or attention deficits could be of interest in elaborating future interventional studies to evaluate the impact of therapeutic strategies, including cognitive rehabilitation, on fatigue.
ABSTRACT
OBJECTIVE: To evaluate temporal trends in early ambulatory status in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: All patients with ICH between 1985 and 2011 were prospectively registered in a population-based registry in Dijon, France, and included in the study. Outcomes of ICH survivors were assessed at discharge from their stay in an acute care ward with the use of a 4-grade ambulation scale. Time trends in ambulation disability and place of discharge were analyzed in 3 periods (1985-1993, 1994-2002, and 2003-2011). Multivariable ordinal and logistic regression models were applied. RESULTS: Five hundred thirty-one patients with ICH were registered, of whom 200 (37.7%) died in the acute care ward. While the proportion of deaths decreased over time, that of patients with ambulation disability increased (odds ratio [OR] 1.67, 95% confidence interval [CI] 0.87-3.23, p = 0.124 for 1994-2002; and OR 1.97, 95% CI, 1.08-3.60, p = 0.027 for 2003-2011 vs 1985-1993 in ordinal logistic regression). The proportion of patients dependent in walking rose (OR 2.11, 95% CI 1.16-3.82, p = 0.014 for 1994-2002; and OR 2.73; 95% CI 1.54-4.84, p = 0.001 for 2003-2011), and the proportion of patients discharged to home decreased (OR 0.49, 95% CI 0.24-0.99, p = 0.048 for 1994-2002; and OR 0.32, 95% CI 0.16-0.64, p = 0.001 for 2003-2011). CONCLUSION: The decrease in in-hospital mortality of patients with ICH translated into a rising proportion of patients with ambulation disability at discharge. A lower proportion of patients returned home. These results have major implications for the organization of postacute ICH care.
Subject(s)
Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/physiopathology , Disabled Persons , Early Ambulation , Hospital Mortality , Aged , Aged, 80 and over , Cerebral Hemorrhage/epidemiology , Community Health Planning , Female , France , Humans , Logistic Models , Male , Middle Aged , Patient Discharge , Retrospective StudiesABSTRACT
BACKGROUND: We aimed to provide a representation of the global burden of stroke. METHODS: All cases of stroke were prospectively identified through the population-based registry of Dijon, France (1987-2012). Attack rates and mortality rates (defined as stroke leading to death within 30 days) were standardized to the European standard. Sex differences and temporal trends were evaluated by calculating rate ratios (RRs). RESULTS: In all, 5,285 stroke cases (52.7% women) were recorded. The standardized attack rate was 98.2/100,000/year and the mortality rate was 12/100,000/year, and both were lower in women than in men (RR 0.67, p < 0.001, and RR 0.70, p < 0.001, respectively). Attack rates increased over time (RR 1.016; 95% CI 1.013-1.020) irrespective of the stroke subtype. In contrast, mortality rates declined (RR 0.985; 95% CI 0.976-0.995) with decreasing rates for ischemic stroke but no change for intracerebral hemorrhage and subarachnoid hemorrhage. The sex gap in both attack and mortality rates remained stable. Between the first (1987-1991) and the last (2007-2012) study periods, the annual number of stroke patients who survived beyond 30 days rose by 55%, Conclusions: Increasing attack rates and decreasing mortality have led to a rise in the number of stroke survivors in the population, thus indicating a growing need for the implementation of dedicated services.
Subject(s)
Brain Ischemia/epidemiology , Intracranial Hemorrhages/epidemiology , Stroke/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Brain Ischemia/mortality , Female , France/epidemiology , Humans , Incidence , Intracranial Hemorrhages/mortality , Male , Middle Aged , Prevalence , Registries , Risk Factors , Sex Factors , Stroke/mortality , Survival RateABSTRACT
INTRODUCTION: Although secondary prevention in patients with arterial vascular diseases has improved, a gap between recommendations and clinical practice may exist. OBJECTIVES: We aimed to evaluate temporal trends in the premorbid use of preventive treatments in patients with ischemic cerebrovascular events (ICVE) and prior vascular disease. METHODS: Patients with acute ICVE (ischemic stroke/TIA) were identified through the population-based stroke registry of Dijon, France (1985-2010). Only those with history of arterial vascular disease were included and were classified into four groups: patients with previous coronary artery disease only (CAD), previous peripheral artery disease only (PAD), previous ICVE only, and patients with at least two different past vascular diseases (polyvascular group). We assessed trends in the proportion of patients who were treated with antihypertensive treatments and antithrombotics at the time of their ICVE using multivariable logistic regression models. RESULTS: Among the 5309 patients with acute ICVE, 2128 had a history of vascular disease (mean age 77.3±11.9, 51% men; 25.1% CAD 7.5% PAD, 39.8% ICVE, and 27.5% poylvascular). A total of 45.8% of them were on antithrombotics, 64.1% on antihypertensive treatment, and 34.4% on both. Compared with period 1985-1993, periods 1994-2002 and 2003-2010 were associated with a greater frequency of prior-to-ICVE use of antithrombotics (adjusted OR=5.94; 95% CI: 4.61-7.65, P<0.01, and adjusted OR=6.92; 95% CI: 5.33-8.98, P<0.01, respectively) but not of antihypertensive drugs. Consistent results were found when analyses were stratified according to the type of history of arterial vascular disease. CONCLUSION: Patients with ICVE and previous vascular disease were still undertreated with recommended preventive therapies.
Subject(s)
Antihypertensive Agents/therapeutic use , Coronary Artery Disease/prevention & control , Fibrinolytic Agents/therapeutic use , Peripheral Arterial Disease/prevention & control , Secondary Prevention/trends , Stroke/prevention & control , Aged , Aged, 80 and over , Female , France , Humans , Male , Middle Aged , Prospective Studies , Registries , Time FactorsABSTRACT
BACKGROUND: We aimed to evaluate the epidemiological features of transient ischemic attack (TIA). METHODS: All TIAs were prospectively collected in Dijon, France, using a population-based registry (2013-2015). TIAs were considered the first-ever in patients who had no previous cerebrovascular events (CVEs); otherwise they were considered recurrent TIAs. Annual incidence (first-ever TIAs) and attack rates (first-ever and recurrent TIAs) were calculated. RESULTS: Four hundred twenty TIAs were registered (255 first-ever and 165 recurrent TIAs, mean age: 74.1 ± 15.7 years). The age-standardized incidence rate (to the 2013 European population) was 61 (95% CI 46-76) and the attack rate was 81 (95% CI 64-99) per 100,000/year. Patients with TIA as a recurrent event had a greater prevalence of risk factors and preventive treatments. However, one third of them were not receiving antithrombotic agents or antihypertensive treatments, and half were not treated with statins at the time of their recurrence. The mean ABCD2 score was 4.3 ± 1.3, and 72% of patients had a high risk of recurrence (score ≥4). In patients with available MRI (23%), an infarct lesion was seen in 15.5%. CONCLUSIONS: TIA is a frequent occurrence and a large proportion of patients have a high risk of recurrence, thus highlighting the need to establish dedicated emergency services to administer prompt secondary prevention.
Subject(s)
Ischemic Attack, Transient/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Prospective Studies , Registries , Risk FactorsABSTRACT
BACKGROUND: Dopamine replacement therapy in PD has been associated with both behavioral addictions and dopamine addiction. OBJECTIVES: To investigate potential association between l-dopa induced neuropsychiatric fluctuations and addictions in PD. METHODS: A cohort of 102 patients with PD suffering from motor complications of l-dopa treatment was prospectively analyzed. We evaluated dopamine addiction, behavioral addictions, and neuropsychiatric fluctuations using the Ardouin scale of behavior in PD. RESULTS: Patients with (n = 51) or without (n = 51) neuropsychiatric fluctuations did not differ in age, disease duration, medication, or UPDRS III motor score during on and off drug condition. Patients with neuropsychiatric fluctuations had a higher H & Y stage in off-drug condition. A multivariate model showed that dopamine addiction (odds ratio: 8.9; P = 0.02) and behavioral addictions (odds ratio: 3.76; P = 0.033) were more frequent in the presence of neuropsychiatric fluctuations. Behavioral addictions and dopamine addiction were more frequent in the presence than in the absence of on-drug euphoria (46% vs. 13.9%; P < 0.001 and 27% vs 6.2 %; P = 0.003), while conversely, no association emerged between dopamine or behavioral addictions and presence of off-drug dysphoria. Patients with neuropsychiatric fluctuations had a poorer quality of life and a more frequent history of anxiety disorder. CONCLUSIONS: The psychostimulant effects of dopamine treatment during on-drug euphoria, rather than avoidance of off-drug dysphoria, appear to drive both behavioral addictions and abuse of medication. © 2017 International Parkinson and Movement Disorder Society.
Subject(s)
Behavior, Addictive/physiopathology , Central Nervous System Stimulants/adverse effects , Depressive Disorder/physiopathology , Dopamine Agents/adverse effects , Euphoria/drug effects , Levodopa/adverse effects , Parkinson Disease/physiopathology , Substance-Related Disorders/physiopathology , Aged , Behavior, Addictive/chemically induced , Dyskinesia, Drug-Induced/physiopathology , Female , Humans , Male , Middle Aged , Parkinson Disease/drug therapy , Prospective StudiesABSTRACT
BACKGROUND AND PURPOSE: We evaluated temporal trends in stroke incidence between men and women to determine whether changes in the distribution of vascular risk factors have influenced sex differences in stroke epidemiology. METHODS: Patients with first-ever stroke including ischemic stroke, spontaneous intracerebral hemorrhage, subarachnoid hemorrhage, and undetermined stroke between 1987 and 2012 were identified through the population-based registry of Dijon, France. Incidence rates were calculated for age groups, sex, and stroke subtypes. Sex differences and temporal trends (according to 5-year time periods) were evaluated by calculating incidence rate ratios (IRRs) with Poisson regression. RESULTS: Four thousand six hundred and fourteen patients with a first-ever stroke (53.1% women) were recorded. Incidence was lower in women than in men (112 versus 166 per 100 000/y; IRR, 0.68; P<0.001), especially in age group 45 to 84 years, and for both ischemic stroke and intracerebral hemorrhage. From 1987 to 2012, the lower incidence of overall stroke in women was stable (IRR ranging between 0.63 and 0.72 according to study periods). When considering stroke subtype, a slight increase in the incidence of ischemic stroke was observed in both men (IRR, 1.011; 95% confidence interval, 1.005-1.016; P=0.001) and women (IRR, 1.013; 95% confidence interval, 1.007-1.018; P=0.001). The sex gap in incidence remained unchanged in ischemic stroke and intracerebral hemorrhage. Conversely, the lower subarachnoid hemorrhage incidence in women vanished with time because of an increasing incidence. CONCLUSIONS: The sex gap in stroke incidence did not change with time except for subarachnoid hemorrhage. Despite lower rates, more women than men experience an incident stroke each year because of a longer life expectancy.
Subject(s)
Brain Ischemia/epidemiology , Cerebral Hemorrhage/epidemiology , Registries/statistics & numerical data , Stroke/epidemiology , Subarachnoid Hemorrhage/epidemiology , Adult , Aged , Aged, 80 and over , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Sex FactorsABSTRACT
Incidence of perinatal arterial stroke (ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage) occurring between 20 weeks of gestation and postnatal day 28 ranges between 20 and 65 cases per 100,000 living births. In children aged 29 days to 18 years old, the total incidence is 1.3 to 4.3 for 100,000 per year. In France, almost 450 children are hospitalized for a stroke each year, among them approximately half have an intracerebral hemorrhage.
Subject(s)
Cerebral Hemorrhage/epidemiology , Stroke/epidemiology , Subarachnoid Hemorrhage/epidemiology , Adolescent , Child , Child, Preschool , France/epidemiology , Humans , Incidence , Infant , Infant, Newborn , PediatricsABSTRACT
OBJECTIVE: To assess whether temporal trends in very early (within 48 hours) case-fatality rates may differ from those occurring between 48 hours and 30 days in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: All cases of ICH that occurred in Dijon, France (151,000 inhabitants), were prospectively collected between 1985 and 2011, using a population-based registry. Time trends in 30-day case fatality were analyzed in 3 periods: 1985-1993, 1994-2002, and 2003-2011. Cox regression models were used to evaluate associations between time periods and case fatality within 48 hours and between 48 hours and 30 days, after adjustments for demographics, risk factors, severity, and ICH location. RESULTS: A total of 531 ICH cases were recorded (mean age 72.9 ± 15.8, 52.7% women). Thirty-day case fatality gradually decreased with time from 40.9% in 1985-1993 to 33.5% 1994-2002 and to 29.6% in 2003-2011 (adjusted hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.47-1.07, p = 0.106, for 1994-2002, and adjusted HR 0.49, 95% CI 0.32-0.73, p < 0.001, for 2003-2011). Over the whole study period, 43.6% of 1-month deaths occurred within the first 48 hours following ICH onset. There was no temporal change in case fatality occurring within the first 48 hours but a decrease in deaths occurring between 48 hours and 30 days was observed with time (HR 0.53, 95% CI 0.31-0.90, p = 0.02, for 1994-2002, and HR 0.32, 95% CI 0.32-0.55, p < 0.01, for 2003-2011, compared with 1985-1993). CONCLUSION: Although 30-day case fatality significantly decreased over the last 27 years, additional improvements in acute management of ICH are needed since very early case-fatality rates (within 48 hours) did not improve.
Subject(s)
Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/mortality , Mortality/trends , Aged , Aged, 80 and over , Cerebral Hemorrhage/classification , Cerebral Hemorrhage/diagnosis , Community Health Planning , Female , Follow-Up Studies , France/epidemiology , Humans , Incidence , Male , Middle Aged , Proportional Hazards ModelsABSTRACT
We aimed to investigate associations between serum thyroid stimulating hormone (TSH) levels and both severity and outcome after ischemic stroke (IS). A total of 731 patients consecutive IS patients were enrolled (mean age 69.4 ± 15.4, 61.6% men), and serum TSH levels were measured at admission and analyzed according to the tertiles of their distribution (<0.822 vs. 0.822-1.6 vs. >1.6 mUI/l). Associations between TSH and both severity at admission (National Institutes of Health Stroke Scale (NIHSS) scores <5 vs. ≥5) and functional outcome at discharge assessed by the modified Rankin Scale were analyzed using logistic regression and ordinal logistic regression models, respectively. High TSH levels were independently associated with both a decreased risk of NIHSS score ≥5 at admission (prevalence proportion ratio = 0.62; 95% CI 0.41-0.94, p = 0.024 for tertile 3 vs. tertile 1). In addition, patients with high TSH levels had a better functional outcome at discharge (OR 0.43; 95% CI 0.30-0.60, p < 0.001 for tertile 2 vs. tertile 1; OR 0.39; 95% CI 0.27-0.56, p < 0.001 for tertile 3 vs. tertile 1). The mechanisms underlying these associations and their potential exploitation in terms of therapeutic strategies need to be explored.
Subject(s)
Cerebral Infarction/blood , Cerebral Infarction/diagnosis , Thyrotropin/blood , Acute Disease , Aged , Aged, 80 and over , Cerebral Infarction/therapy , Disability Evaluation , Female , Humans , Male , Middle Aged , Prognosis , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Several trials and meta-analyses have recently demonstrated the superiority of endovascular therapy over standard medical treatment in patients presenting with acute ischemic stroke. In order to offer the best possible treatment to a maximum number of patients, many stroke care networks probably have to be reorganized. After analyzing the reliability of data in the literature, an algorithm is suggested for a pre-hospital and in-hospital alert system to improve the timeliness of subsequent treatment: a drip-and-ship approach. SUMMARY: Five recent well-designed randomized studies have demonstrated the benefit of endovascular therapy associated with intravenous fibrinolysis by recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke with confirmation by recent meta-analyses. The keys for success are a very short time to reperfusion, within 6 h, a moderate to severe pre-treatment deficit (National Institute of Health around 17), cerebral imaging able to identify proximal large vessel occlusion in the anterior circulation, a limited infarct core and a reversible penumbra, the use of the most recent devices (stent retriever) and a procedure that avoids general anesthesia, which reduces blood pressure. To meet these goals, every country must build a national stroke infrastructure plan to offer the best possible treatment to all patients eligible for intravenous fibrinolysis and endovascular therapy. The plan may include the following actions: inform the population about the first symptoms of stroke, provide the call number to improve the timeliness of treatment, increase the number of comprehensive stroke centers, link these to secondary and primary stroke centers by telemedicine, teach and train paramedics, emergency doctors and radiologists to identify the stroke infarct, proximal large vessel occlusion and the infarct core quickly, train a new generation of endovascular radiologists to improve access to this therapy. KEY MESSAGE: After 20 years of rt-PA, this new evidence-based therapy is a revolution in stroke medicine that will benefit patients. However, a new robust and multi-disciplinary care strategy is necessary to transfer the scientific data into clinical practice. It will require reorganization of the stroke infrastructure, which will include comprehensive stroke centers and secondary and primary stroke centers. The winners will be patients with severe stroke.
Subject(s)
Endovascular Procedures/methods , Hospital Administration/methods , Stroke/therapy , Thrombectomy/methods , Thrombolytic Therapy/methods , Fibrinolytic Agents/therapeutic use , Humans , Reproducibility of Results , Stents , Stroke/diagnosis , Thrombectomy/instrumentation , Tissue Plasminogen Activator/therapeutic useABSTRACT
BACKGROUND: Primary leptomeningeal gliomatosis (PLG) is a poorly recognized tumor of the central nervous system. OBJECTIVE: To describe the histopathological, immunohistochemical, and molecular features of PLG. METHODS: Results of our multicentric retrospective study of 6 PLG cases (3 pediatric and 3 adult) were compared with literature data. RESULTS: The mean age was 54.7 years for adults and 8.7 years for children, with 3 males and 3 females. Clinical symptoms were nonspecific. Cerebrospinal fluid analyses showed a high protein level often associated with pleocytosis but without neoplastic cells. On neuroimaging, diffuse leptomeningeal enhancement and hydrocephalus were observed, except in 1 case. PLG was mostly misinterpreted as infectious or tumoral meningitis. The first biopsy was negative in 50% of cases. Histopathologically, PLG cases corresponded to 1 oligodendroglioma without 1p19q codeletion and 5 astrocytomas without expression of p53. No immunostaining for IDH1R132H and no mutations of IDH1/2 and H3F3A genes were found. Overall survival was highly variable (2-82 months) but seems to be increased in children treated with chemotherapy. CONCLUSION: This study shows the difficulties of PLG diagnosis. The challenge is to achieve an early biopsy to establish a diagnosis and to begin a treatment, but the prognosis remains poor. PLG seems to have a different molecular and immunohistochemical pattern compared with intraparenchymal malignant gliomas.