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Biomedical subjects

José M Ferro

Publications and source records attributed to José M Ferro.

At least 19 recordsLinked to original sources

Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study.

BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population. METHODS: We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline. CONCLUSION: Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Aged↗

Predictors of outcome in patients with cerebral venous thrombosis and intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Although intracerebral hemorrhages are frequent in patients with cerebral venous thrombosis, and lead to worse outcome, predictors of outcome in cerebral venous thrombosis patients with intracerebral hemorrhages have never been evaluated in adequately powered studies. METHODS: This study was conducted as a part of the International Study on Cerebral Vein and Dural Sinus Thrombosis. We evaluated predictors of outcome in cerebral venous thrombosis patients who had an "early intracerebral hemorrhage," ie, intracerebral hemorrhages already present at time of diagnosis of cerebral venous thrombosis by a logistic regression analysis, with a modified Rankin scale 3 to 6 at month 6 as dependent variable. The same analysis was performed with "delayed intracerebral hemorrhages," ie, intracerebral hemorrhages that occurred after the diagnosis of cerebral venous thrombosis, as dependent variable. RESULTS: Of 624 patients recruited in International Study on Cerebral Vein and Dural Sinus Thrombosis, 245 (39%) had an early intracerebral hemorrhage: at month 6, 51 (21%) of them had a modified Rankin Scale 3 to 6. Independent predictors of having modified Rankin scale 3 to 6 at month 6 were older age (adjusted odds ratio for 1-year increase in age, 1.05; 95% CI, 1.02 to 1.08); male gender (adjusted odds ratio, 3.25; 95% CI, 1.29 to 8.16); having a deep cerebral venous system thrombosis (adjusted odds ratio, 5.43; 95% CI, 1.67 to 17.61) or a right lateral sinus thrombosis (adjusted odds ratio, 2.56; 95% CI, 1.03 to 6.40); and having a motor deficit (adjusted odds ratio, 2.94; 95% CI, 1.21 to 7.10). Of the 36 patients who had a delayed intracerebral hemorrhage, those who had a modified Rankin scale 3 to 6 at month 6 were less likely to have received heparin at the acute stage, and more likely to have had early intracerebral hemorrhage. CONCLUSIONS: Among patients with early intracerebral hemorrhage, those who were older, men, had a thrombosis of the deep cerebral venous system or of the right lateral sinus, and a motor deficit were at higher risk for death or dependency at month 6. This subgroup of patients with predictors of poor outcome can be the target for new therapeutic strategies.

Adolescent↗

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study.

BACKGROUND: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. OBJECTIVE: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. RESULTS: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Aged↗

Update on intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is a common and serious disease. About 1 to 2 out of 10 patients with stroke have an ICH. The mortality of ICH is higher than that of ischaemic stroke. Only 31% are functionally independent at 3 months. Only 38% of the patients survive the 1(st) year. The cost of ICH is high. Hypertension is the major risk factor, increasing the risk of ICH about 4x. Up to half of hypertensive patients who suffer a ICH are either unaware of their hypertension, non-compliant with the medication or fail to control periodically their blood pressure levels Microbleeds and white matter changes are MRI markers of the risk of ICH. ICH has 3 main pathophysiological phases: arterial rupture and haematoma formation, haematoma enlargement and peri-haematoma oedema. Up to 40% of the haematomas grow in the first hours post-rupture. ICH growth is associated with early clinical deterioration. Two randomised clinical trials (RCTs) demonstrated that treatment with rFVIIa limited haematoma growth and improved outcome, but was associated with a increase in thromboembolic complications. Ventricular drainage with thrombolytics might improve outcome for patients with intraventricular bleeding. A large RCT and meta-analysis failed to show a benefit of surgery over conservative treatment in acute ICH.

Cerebral Amyloid Angiopathy↗

Other neuroprotective therapies on trial in acute stroke.

New neuroprotective agents on trial may potentially offer benefit to stroke patients without the associated hemorrhagic risk of thrombolytic therapy. Clinical investigation of these drugs has been designed to obtain the highest probability of success, or concentrates on the salvageable ischemic brain and use infarct growth on MRI as a surrogate end-point. Nine substances in 10 trials are currently being tested in three therapeutical strategies in patients with acute ischemic stroke. These strategies focus on: (1) the optimal management of serum glucose with the infusion of glucose, insulin and potassium to induce and maintain euglycemia; (2) the modulation of the inflammatory response with recombinant human interferon-beta(1a), and (3) interfering with the ischemic cascade using magnesium, albumin, the metal iron chelator DP-b99, the AMPA receptor antagonist zonampanel, the serotonin agonists repinotan and piclozotan, the free radical scavenger cerovive, and the membrane modulator citicoline. Future directions should develop neuroprotective compounds that are safe and well tolerated, are effective in a broad range of patients and can be used with or without rt-PA.

Anti-Inflammatory Agents↗

Denial in the first days of acute stroke.

Denial is a disorder of self-awareness that is frequent after acute stroke, with potential negative influence in the care of patients. The aim of this study was to describe the presence and correlates of denial in acute stroke. We assessed denial in a sample of 180 consecutive acute stroke patients (< or =4 days) and in a control group of 50 acute coronary patients using the Denial of Illness Scale (DIS).41% (74) acute stroke patients (mean DIS score=4.1, SD=2.2, range 0 to 10) and 24% (12) acute coronary patients (mean DIS score=3.2, SD=1.5, range 0 to 10) presented denial (chi(2)=4.19, p=.04; U=3405.50, p=.01). Denial was more frequent and severe in patients with lower educational level (chi(2) = 5.04, p=.04; U=2110.50; p=.01), neglect (chi(2) = 21.38, p=.00; U=1130.50; p=.00), cognitive impairment (chi(2) = 6.27, p=.02; U=1181.50; p=.01) and after hemispherical lesions (chi(2) =4.68, p=.05; U=1982.50; p=.04). In logistic regression low educational level, neglect and cognitive impairment were independent factors predicting denial in stroke patients (R(2)= 21%). Patients with denial can express depressive symptoms. Patients with denial had a worse outcome at discharge (chi(2) =4.91, p=.04; U=2918.00; p=.03). Denial is a frequent phenomenon after acute stroke. We propose that there is a multifactorial model for the emergence of denial, lower educational as a predisposing condition, and acute stroke due to hemisphere lesion and causing neglect and cognitive impairment as precipitating events. All these factors limit patients' assessment of their condition and body functions.

Acute Disease↗

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Age Factors↗

Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study.

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

Activities of Daily Living↗

Depression in acute stroke.

OBJECTIVE: Depression is one of the most frequent neuropsychiatric disturbances in stroke patients. The clinical aspects and correlations of depression in the first days after acute stroke are less known. This study aimed to 1) assess the frequency of depression, 2) describe the profile of depression of stroke patients and 3) analyze the relation between depression and demographic, predisposing and precipitating conditions, and clinical and imaging data, in acute stroke patients. METHODS: We used the Montgomery-Asberg Depression Rating Scale to assess depression in 178 consecutive acute ( 0.45) of depression between control subjects and acute stroke patients. CONCLUSIONS: Depression was present in almost one-half of the acute stroke patients and was related to previous mood disorder but not not to stroke type or location. Apathy/loss of interest was the predominant clinical feature.

Aged↗

Cerebral vein and dural sinus thrombosis in elderly patients.

BACKGROUND AND PURPOSE: The clinical features and prognosis of cerebral vein and dural sinus thrombosis (CVT) in elderly patients have not been previously described. METHODS: In a multicenter prospective observational study, we compared clinical and imaging features, risk factors, and outcome of adult patients aged <65 (young and middle-aged patients) and > or =65 years (elderly patients). RESULTS: A total of 624 adult patients with CVT were registered and followed-up for a median of 16 months. Fifty-one (8.2%) were aged > or =65 years. Presentation as an isolated intracranial hypertension syndrome was less frequent in elderly patients (4/51 versus 139/573, P=0.008), whereas depressed consciousness (17 versus 97, P=0.005), and mental status changes (22 versus 115, P=0.001) were more frequent in the elderly. The prognosis of elderly patients was considerably worse than that of younger patients, as only 49% of elderly patients made a complete recovery (versus 82% in younger patients), whereas 27% died and 22% were dependent at the end of follow-up (versus 7 and 2% respectively in younger patients). Carcinoma (5 cases) was more frequent as a risk factor for CVT in elderly patients (P=0.017). During follow-up, elderly patients were more likely to experience thrombotic events (HR=4.8, 95% CI=1.9 to 11.9) and were less likely to experience severe headaches (HR=0.2, 95% CI=0.02, 0.97). CONCLUSIONS: Elderly patients with CVT have a distinctive clinical presentation: isolated intracranial hypertension is uncommon, whereas mental status and alertness disturbances are common. The prognosis of CVT is worse in elderly patients.

Adult↗

Causes and predictors of death in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: The causes of death of patients with cerebral venous thrombosis (CVT) have not been systematically addressed in previous studies. We aimed to analyze the causes and predictors of death during the acute phase of CVT in the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) to identify preventable or treatable causes. METHODS: ISCVT is a multinational, prospective, observational study including 624 patients with CVT occurring between May 1998 and May 2001, in which 27 patients (4.3%) died during the acute phase, 21 (3.4%) within 30 days from symptom onset. Inclusion forms and a questionnaire assessing the causes of death were analyzed. A logistic regression analysis was performed to identify the predictors of death within 30 days from symptom onset of CVT. RESULTS: Median time between onset of symptoms and death was 13 days and between diagnosis and death, 5 days. Causes of death were mainly transtentorial herniation due to a unilateral focal mass effect (10 patients) or to diffuse edema and multiple parenchymal lesions (10 patients). Independent predictors of death were coma (odds ratio [OR], 8.8; 95% confidence interval [CI], 2.8 to 27.7), mental disturbance (OR, 2.5; 95% CI 0.9 to 7.3), deep CVT thrombosis (OR, 8.5; 95% CI, 2.6 to 27.8), right intracerebral hemorrhage (OR, 3.4; 95% CI, 1.1 to 10.6), and posterior fossa lesion (OR, 6.5; 95% CI, 1.3 to 31.7). Worsening of previous focal or de novo focal deficits increased the risk of death. CONCLUSIONS: The main causes of acute death were neurologic, the most frequent mechanism being transtentorial herniation.

Acute Disease↗

Delay in hospital admission of patients with cerebral vein and dural sinus thrombosis.

Factors influencing early hospital admission have been described for several stroke types but not for cerebral vein and dural sinus thrombosis (CVT). CVT is more difficult to diagnose than arterial stroke; delay in hospital admission may postpone CVT treatment. The purposes of this study were: (1) to describe the delay between the onset of symptoms and hospital admission of patients with CVT, and (2) to identify the variables that influence that delay. We registered the interval (days) between the onset of symptoms and hospital admission in 91 consecutive patients admitted to 20 Portuguese hospitals between June 1995 and June 1998. We also studied the impact of admission delay on treatments (prescription of anticoagulants and the number of days elapsed between the onset of symptoms and start of anticoagulation and admission). Median admission delay was 4 days. Twenty-two (25%) patients were admitted within 24 h. Two thirds of the patients were admitted within 7 days and 75% within 13 days. In multiple logistic regression analysis, admission within 24 h was positively associated with mental status disorder (delirium or abulia; OR = 4.59; 95% CI = 1.41-14.89) and negatively associated with headache (OR = 0.03; 95% CI = 0.00-0.32). Presentation as isolated intracranial hypertension was associated with admission delay of more than 4 days (OR = 2.63; 95% CI = 0.97-7.14). Papilloedema was associated with an admission delay of more than 13 days (OR = 4.69; 95% CI = 1.61-13.61). There was no association between admission delay and the proportion of anticoagulated patients. The interval between onset of symptoms and start of anticoagulation was shorter in patients admitted earlier (p = 0.0001, for either admission within 24 h, 4 or 13 days). There is a considerable delay until the clinical picture associated with CVT is recognised as justifying hospital admission, especially when patients present with symptoms identical to isolated intracranial hypertension syndrome.

Anticoagulants↗

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗

Delirium in acute subarachnoid haemorrhage.

BACKGROUND: Delirium may be a presenting feature in acute subarachnoid haemorrhage (SAH). The aim of this study was to investigate the risk factors for delirium in acute SAH and to analyse the relation between delirium and location and amount of haematic densities and hydrocephalus. METHODS: We assessed delirium in a sample of 68 consecutive patients with acute (< or =4 days) SAH (33 aneurysmal, 33 non-aneurysmal, including 9 with perimesencephalic haemorrhage), before aneurysmal treatment, using DSM-IV-R criteria and the Delirium Rating Scale (DRS). DRS scores were related to: (1) the total amount of haematic densities at 10 basal cisterns/fissures and in the 4 ventricles, using a validated rating scale, (2) the haematic densities in the prepontine cistern and the convexity of the brain and (3) hydrocephalus, using the bicaudate index, obtained from a review of admission CT scans. RESULTS: Eleven acute SAH patients presented with delirium. Older age (U = 316.5, p = 0.04), alertness disturbance (chi(2) = 5.1, p = 0.02, OR = 7.6, 95% CI = 1.5-37.3), aphasia (U = 61.5, p = 0.007) and a Hunt and Hess score >2 (U = 362.5, p = 0.02) were associated with delirium. Higher amounts of intraventricular haematic densities (chi(2) = 4.43, p = 0.04, U = 158, p = 0.001) and hydrocephalus (U = 215, p = 0.009) were also associated with higher DRS scores. Two delirious patients had basofrontal haematomas. CONCLUSIONS: Delirium was detected in 16% of acute SAH patients. Intraventricular bleeding, hydrocephalus and basofrontal haematomas contribute to the pathogenesis of delirium, through damage to anatomical networks subserving sustained attention, declarative memory and the expression of emotional behaviour.

Acute Disease↗