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Biomedical subjects

Gian Luigi Lenzi

Publications and source records attributed to Gian Luigi Lenzi.

At least 19 recordsLinked to original sources
PubMed2006

Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial.

BACKGROUND: Intravenous tissue plasminogen activator is the only approved specific treatment for acute ischaemic stroke. Ancrod, a natural defibrinogenating agent from snake venom, has proved to have a favourable effect when given within 3 h after an acute ischaemic stroke. The European Stroke Treatment with Ancrod Trial was undertaken to assess the effects of ancrod when given within 6 h. METHODS: 1222 patients with an acute ischaemic stroke were included in this randomised double-blind placebo-controlled trial. Brain CT scans were done to exclude intracranial haemorrhages and large evolving ischaemic infarctions. Patients were randomly assigned ancrod (n=604) or placebo (n=618). The primary outcome was functional success at 3 months (survival, Barthel Index of 95 or 100, or return to prestroke level). The analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, trial number NCT00343174. FINDINGS: Functional success at 3 months did not differ between patients given ancrod (42%) and those given placebo (42%) (p=0.94, OR=0.99, 95% CI, 0.76-1.29). INTERPRETATION: On the basis of our findings, ancrod should not be recommended for use in acute ischaemic stroke beyond 3 h.

Aged↗
PubMed2006

The ruler is dead: an analysis of carotid plaque motion.

Factors involved in atherosclerotic plaque progression are still a topic of hot debate. With the advance of new ultrasound techniques it has been possible to identify atherosclerotic plaque characteristics that may reflect a higher risk of vulnerability. Among the various proposed mechanisms, one of the least investigated is plaque motion, i.e. plaque stability in respect to the arterial wall. We report here two asymptomatic patients with internal carotid stenosis that showed differences in plaque motion, a finding that could determine a change in their future treatment.

Aged↗
PubMed2005

Late motor recovery is influenced by muscle tone changes after stroke.

OBJECTIVES: To evaluate the time course of motor recovery in a poststroke period ranging from 2 to 6 months and its correlation with both the severity of motor deficit and the muscle tone disturbances (flaccidity or spasticity) of the affected limbs. DESIGN: Prospective cohort study. SETTING: A comprehensive rehabilitation hospital. PARTICIPANTS: Forty consecutive stroke patients (21 men, 19 women) with first ischemic stroke who met the inclusion criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Change in motor deficit as evaluated by the Adams Hemispheric Stroke Scale. RESULTS: Stepwise regression analysis indicated that the most significant factors influencing motor recovery were the time elapsed since stroke and muscle tone. CONCLUSIONS: Rehabilitation of stroke patients is more effective in the first months after the event rather than later, considering the significant correlation observed between motor recovery and time elapsed since stroke. Flaccid patients appear to need 3 months or more before reaching the final plateau, because motor recovery occurs later and/or proceeds more slowly, whereas outcomes for spastic patients with spasticity appears to occur in the first months after stroke.

Adult↗
PubMed2005

Update on stroke.

PURPOSE OF REVIEW: This review highlights the progress achieved in stroke during the last year, and emphasizes recent controversies concerning its pathophysiology, therapy and secondary complications. RECENT FINDINGS: Studies published in 2004 provided new insights into the therapeutic window and ischemic penumbra, thrombolysis therapy, uncommon risk factors for stroke, and neuropsychological post-stroke complications. Despite the diffusion-perfusion mismatch remaining the most widely used technique to identify thresholds for ischemic penumbra and irreversible brain tissue damage, new imaging such as arterial spin-labeling perfusion and computed tomographic perfusion may define this impaired tissue more accurately. New studies assessed the relation of the interval from stroke onset to start intravenous thrombolysis treatment (tissue plasminogen activator) on favorable 3-month outcome, and on the occurrence of clinically relevant parenchymal hemorrhage: the benefit of tissue plasminogen activator could extend beyond 3 h, but with a few risks. Systemic inflammations and infections have been found to be associated with a substantial increase in the risk of developing vascular events, supporting the concept that systemic inflammation itself alters the probability of stroke occurrence. Recent literature concerning neuropsychological post-stroke complications focused mainly on the concept of mixed dementia and confirmed that mood disorders are common after stroke, and interfere with its long-term outcome. SUMMARY: Significant advances have been made during the last year in determining more accurately the therapeutic window, using new strategies and clinical markers. Moreover, new light has been thrown on less common stroke risk factors, and neuropsychological post-stroke complications.

Journal Article↗
PubMed2004

Catechol-O-methyltransferase gene polymorphism is associated with risk of psychosis in Alzheimer Disease.

There is emerging evidence that psychosis in Alzheimer Disease (AD) represents a clinically relevant phenotype with a distinct biological process. It has been reported that a functional polymorphism of the catechol-O-methyltransferase (COMT) gene predisposes to an increased risk for schizophrenia and likely to psychosis susceptibility. Aim of this study was to evaluate functional COMT genetic variation as a risk factor for psychosis in Alzheimer Disease. One hundred eighty-one AD patients and 208 age-matched controls underwent clinical and neuropsychological examination, behavioural and psychiatric disturbances evaluation, and ApoE and COMT genotyping. The distribution of COMT genotypes did not significantly differ in AD compared to controls. Among patients with psychosis (32.6%), 88.1% were COMT*H carriers (COMT H/H or COMT H/L, p < .01). The Odds Ratio (OR) for risk of psychosis in COMT*H carriers was 2.66 (confidence interval, CI 95%: 1.6-6.62), taking into account possible confounding factors. A comparable influence of COMT polymorphism on psychosis over the course of the disease was reported. These findings suggest that COMT polymorphism influences on the risk of psychosis since the early stages, and claims for the possibility to identify distinct phenotypes on genetic basis among AD patients.

Aged↗
PubMed2004

Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers.

BACKGROUND: The adverse effects of the antiepileptic drugs (AEDs) originally developed are well known, while those of the newer AEDs remain unclear. OBJECTIVE: To investigate clinical, cognitive, and neurophysiologic effects of carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. METHODS: A double-blind crossover study was conducted in 10 volunteers. Eight-day treatment with carbamazepine, oxcarbazepine, levetiracetam, or placebo was administered in random order. Drug doses were titrated gradually to the daily target doses on day 7: carbamazepine 800 mg, oxcarbazepine 1200 mg, and levetiracetam 1500 mg. At baseline and at the end of each treatment period, participants underwent cognitive and neurophysiologic assessment. A washout period of 14 days between treatment periods was conducted. RESULTS: More adverse events were self-reported with carbamazepine (63%) than the other treatments (oxcarbazepine 12%, levetiracetam 20%, placebo 5%; p < 0.001 between the 4 groups). Carbamazepine induced the greatest motor slowing (p = 0.002), followed by oxcarbazepine (p = 0.01). Levetiracetam left baseline motor speed unchanged. All AEDs increased attention span from baseline values as shown on the Stroop test. Quantitative electroencephalogram (EEG) analysis showed that carbamazepine significantly increased the delta-theta power and reduced the frequency of alpha rhythm; oxcarbazepine induced smaller changes than carbamazepine. Levetiracetam did not change any EEG measurements. On color visually evoked potential (VEP) tests, carbamazepine induced a constant slowing of P1 latency, while oxcarbazepine induced changes only after the blue-black pattern. All color VEP measures for volunteers receiving levetiracetam were almost unchanged. CONCLUSIONS: After short-term treatment in healthy volunteers, carbamazepine induced major clinical and neurophysiologic changes. Oxcarbazepine was better tolerated than carbamazepine. Levetiracetam interfered least with clinical and neurophysiologic test results.

Adult↗
PubMed2004

The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis: a monthly MRI study after triple-dose gadolinium-DTPA.

OBJECTIVE: To examine the relationship between inflammation and brain atrophy in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: Monthly triple-dose gadolinium (Gd/DTPA)-enhanced MRI scans over 6 months were obtained in 62 consecutive CIS patients with an abnormal baseline MRI scan. Subsequently MRI was performed at months 12 and 18. Patients who developed a clinically definite MS (i. e., a second clinical episode) ended the study at the time of the relapse. For each scan, the number and volume of newly active lesions (Gd-enhancement/new or newly enlarging T2 lesion that did not enhance), and the number and volume of T2 hyperintense lesions (T2-LL) and T1-black holes (T1-LL) were calculated. The percentage of brain volume changes (PBVC) was assessed using a fully automated technique (SIENA; Structural Image Evaluation using Normalization of Atrophy). RESULTS: Twenty-four (39%) developed clinically definite MS by month 18. Thirty-eight (61%) were relapsefree and completed the MRI follow-up. Relapse-free patients showed a progressive median increase between baseline and month 18 in T1-LL (25%, p<0.001), but not in T2-LL (8.5%, p=ns). PBVC decreased by 1.1% (p<0.001) in a time-dependent pattern (Kendall coefficient of concordance=0.85). Exploratory subgroup analyses showed a trend towards progressive decreases in brain volume in active patients (i. e., those with at least one newly active lesion during monthly MRI scanning; Spearman's R=-0.61; p<0.001), but not among inactive patients (Spearman's R=-0.10; p=0.53). Significant differences in median brain volume changes between the active and inactive patient groups were found at months 12 and 18; the difference detected at month 6 was not significant. The cumulative number and volume of new Gd-enhancing lesions developed during the 6 months of frequent MRI scanning were highly correlated with PBVC over the 18-month period (Spearman R values were 0.73 and 0.85, respectively). The strongest predictor of PBVC at 18 months was the cumulative volume of newly active lesions during frequent MRI scanning [ss=-0. 83, standard error (SE)=0.07, p<0.001]. CONCLUSIONS: This study shows that visible inflammation as detected by monthly, triple-dose Gd-enhanced MRI is an important factor in the pathogenesis of brain tissue loss in CIS patients. However, inflammation and brain atrophy do not proceed in parallel: atrophy appeared only after a delay of months following acute inflammation. Frequent MRI scanning allows for the detection of CIS patients who will develop brain atrophy in the short-term.

Adolescent↗
PubMed2004

Acute stroke effects on emotions: an interpretation through the mirror system.

PURPOSE OF REVIEW: The most recent reports on emotional consequences of stroke are hereby reviewed and analyzed. In particular the interpretation of some neurological presentations found in stroke patients, such as athymormia, dysprosody, emotional incontinence and emotional blunting is discussed. As current theories on mental functions do not provide satisfactory explanations for the above syndromes, a novel interpretative framework is proposed, based on neuropsychological experimental data on the 'mirror system'. RECENT FINDINGS: Recent findings support both the fundamental role of the mirror system in imitative processes as well as the relevance of imitation for the emotional part of human personality and behavior. SUMMARY: The mirror system appears to be of paramount relevance for empathy and social behavior. The model of analysis-by-synthesis is here discussed, together with neurological presentations resulting from stroke induced impairments of the mirror system. Speculations for further researches are also proposed.

Affect↗
PubMed2003

Neural mechanisms of empathy in humans: a relay from neural systems for imitation to limbic areas.

How do we empathize with others? A mechanism according to which action representation modulates emotional activity may provide an essential functional architecture for empathy. The superior temporal and inferior frontal cortices are critical areas for action representation and are connected to the limbic system via the insula. Thus, the insula may be a critical relay from action representation to emotion. We used functional MRI while subjects were either imitating or simply observing emotional facial expressions. Imitation and observation of emotions activated a largely similar network of brain areas. Within this network, there was greater activity during imitation, compared with observation of emotions, in premotor areas including the inferior frontal cortex, as well as in the superior temporal cortex, insula, and amygdala. We understand what others feel by a mechanism of action representation that allows empathy and modulates our emotional content. The insula plays a fundamental role in this mechanism.

Adult↗
PubMed2003

High cholesterol affects platelet APP processing in controls and in AD patients.

Alzheimer disease (AD) is characterised by a decrease of platelet Amyloid Precursor Protein forms ratio (APPr), which parallels symptoms' severity. Recent studies have suggested that cholesterol might play a role in the pathophysiology of AD by modulating Abeta production. Aim of this study was to evaluate the relationship between serum cholesterol levels and platelet APP processing in controls and AD. Sixty AD patients and 45 age-matched controls (CTRL) were investigated. Neuropsychological assessment, cholesterol dosage and APP forms' evaluation were performed on each subject. CTRL showed lower serum cholesterol levels compared to AD (P<0.01) and higher mean APPr scores (P<0.0001). Hypercholesterolaemic AD patients showed lower APPr scores compared to normocholesterolaemic AD patients matched for disease severity (0.31+/-0.16 versus 0.45+/-0.28; P<0.05), since the early stage of the disease. In AD, cholesterol levels influence APPr independently of disease severity. These findings confirm the association between cholesterol and AD, and suggest that in vivo cholesterol affects APP processing by interfering with its maturation.

Aged↗
PubMed2002

Microvascular damage and platelet abnormalities in early Alzheimer's disease.

Accumulating evidence from epidemiological and clinical studies suggests that vascular risk factors may be involved in Alzheimer disease (AD). Although the precise contribution of vascular disturbances to the pathogenesis of AD is still unclear, various biochemical and neuropathological data strengthen the view that cerebrovascular deficiencies such as reduced blood supply to the brain and disrupted microvascular integrity in brain parenchyma play a direct or intermediate role in the chain of events ending with a dementia syndrome. The present review focuses on platelet abnormalities and hemostatic alterations in AD. In particular, data from our group, along with current literature, are discussed with regard to the evidence of platelets amyloid precursor protein (APP) processing disturbances in early AD as well as to the recent observations of increased serum levels of thrombomodulin and sE-selectin, which are sensitive markers of endothelial dysfunction. These findings strongly indicate that platelet dysfunction and microvasculature deficiencies occur rather early during the course of AD, thus suggesting a further link between AD-related processes and vascular disorders.

Alzheimer Disease↗
PubMed2002

Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease.

CONTEXT: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls. OBJECTIVE: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. SETTING: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. DESIGN AND METHODS: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. RESULTS: Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. CONCLUSIONS: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.

Aged↗
PubMed2002

Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis.

The objectives of this study were to assess whether cortical motor reorganization in the early phase of multiple sclerosis (MS) is correlated with the clinical presentation and with specific damage to the corticospinal tract. Twenty patients with clinically isolated syndrome (CIS) and serial MR findings indicative of MS were selected. In 10 patients the CIS was hemiparesis (group H), and in 10 patients the CIS was optic neuritis (group ON). There were no significant differences in age, disease duration, total T2 lesion load (LL), and total T1 LL between group H and group ON. Ten age-matched healthy subjects served as controls (group C). All subjects were submitted to fMRI during a sequential finger-to-thumb opposition task of the right hand. Group H showed a significantly higher EDSS score and T1 LL calculated along the corticospinal tract than group ON. Three-group comparison by ANOVA showed significantly higher activation in group H than in the other two groups (P < 0.001). Significant foci were located in the sensory-motor cortex (BA 1-4), the parietal cortex (BA 40), the insula of the ipsilateral hemisphere, and the contralateral motor cortex (BA 4/6). Group ON showed, although at a lower level of significance (P < 0.01), higher activation of the contralateral motor-related areas than group C. Multiple regression analysis showed that T2 and T1 LL along the corticospinal tract and time since clinical onset positively correlated with activation in motor areas in both cerebral hemispheres (P < 0.005). Total T2 LL positively correlated with activation in motor areas in the contralateral hemisphere (P < 0.005). Total T1 LL and EDSS did not show any significant correlation. More severe specific damage to the motor pathway in patients with previous hemiparesis may explain the significantly higher involvement of ipsilateral motor areas observed in group H than in group ON. Furthermore, the significant correlation between the time since clinical onset and activation in motor areas suggests that cortical reorganization develops gradually in concomitance with the subclinical accumulation of tissue damage.

Adult↗
PubMed2002

A longitudinal study of MR diffusion changes in normal appearing white matter of patients with early multiple sclerosis.

BACKGROUND AND PURPOSE: The stage at which normal appearing white matter (NAWM) abnormalities first appear in multiple sclerosis (MS) is not clear. The aim of our study was to monitor water diffusion changes over time in NAWM of patients with early MS. METHODS: Out of a consecutive series of patients enrolled in a MR study on clinically isolated syndrome (CIS), we selected 19 subjects who had completed a one year follow-up. The MR scans obtained at baseline and at 12 months were reviewed according to the new criteria on the diagnosis of MS. Lesion load on T2 and T1 weighted images and the trace of the apparent diffusion coefficient in NAWM were measured both at baseline and at 12 months in patients and in 12 healthy controls. RESULTS: In three patients the diagnosis of MS was done at baseline based on MR. Thirteen patients developed MS during the study and in three patients the diagnosis remained "possible MS." TADC in NAWM in patients was significantly higher than in controls at the 12 months' follow-up but not at baseline (controls mean tADC +/- sd = 0.745 +/- 0.02 mm(2)/sec x 10(-3); patients mean tADC(12) +/- sd = 0.767 +/- 0.02 mm(2)/sec x 10(-3); p < 0.02). TADC and T2 lesion load at 12 months were significantly correlated (p < 0.01). Patients exhibiting tADC(12) above a confidence interval had a significantly greater EDSS score at the same time period (EDSS(12) +/- sd = 1.9 +/- 0.5 and = 1.1 +/- 0.4 respectively; p < 0.01). CONCLUSIONS: This study suggests that diffusion MR cannot detect alterations in NAWM of patients with a CIS suggestive of MS. After one year, when most patients develop MS, diffusion MR abnormalities in NAWM become apparent. These abnormalities are correlated with T2 lesion load and may contribute to neurological impairment.

Adult↗
PubMed2002

Cortical motor reorganization after a single clinical attack of multiple sclerosis.

In order to evaluate whether cortical motor reorganization occurs in the earliest phase of multiple sclerosis, we studied patients after a first clinical attack of hemiparesis. From a consecutive series of 70 patients enrolled in a study of patients with clinically isolated syndrome and serial MRI findings indicative of multiple sclerosis, we retrospectively selected 10 patients with hemiparesis as the onset symptom and no further clinical episode [mean age 32 +/- 9 years, disease duration 24 +/- 14 months, median Expanded Disability Status Score (EDSS) 1.25]. Ten age-matched, healthy subjects served as controls. Each subject was submitted to two functional MRI trials (one per hand) using a 1.5 T magnet during a sequential finger-to-thumb opposition task. Image analysis was performed using SPM99 software. Movements of both the 'affected' and the 'unaffected' hand activated significantly larger areas in patients than in controls in both the contralateral and ipsilateral cortical motor areas. Patients activated a greater number of foci than controls during both the right-hand and the left-hand movement. Most of these foci were located in cortical areas which were less or not at all activated in controls, such as the lateral premotor cortex [Brodmann area (BA) 6], the insula and the inferior parietal lobule (BA 40). Between-group analysis of patients versus controls showed significant (P < 0.001) foci in these areas, principally located in the ipsilateral hemisphere during right-hand movement and in both the cerebral hemispheres during left-hand movement. Time since clinical onset showed a significant positive correlation with the extent of activation in the ipsilateral motor areas (P = 0.006) during the right-hand movement and with the extent of activation in both the ipsilateral (P = 0.02) and contralateral (P = 0.006) motor areas during the left-hand movement. The T(1) lesion load along the motor pathway showed a significant positive correlation (P = 0.007) with the extent of activation in the contralateral motor areas during right-hand movement. Our study shows functional adaptive changes that involve both the symptomatic and asymptomatic hemisphere during a simple motor task in patients who had suffered a single clinical attack of hemiparesis. The extent of these changes increased with the time elapsed since disease onset and the severity of brain damage.

Acute Disease↗