Biomedical subjects

Giorgio Silvestrelli

Publications and source records attributed to Giorgio Silvestrelli.

12 recordsLinked to original sources

PubMed2005

Neurotransmitter deficits in behavioural and psychological symptoms of Alzheimer's disease.

Behavioural and psychological symptoms of dementia (BPSD) occur in 50-90% of Alzheimer's disease (AD) patients. Imbalance of different neurotransmitters (acetylcholine, dopamine, noradrenaline and serotonin), involvement of specific brain regions responsible for emotional activities (parahippocampal gyrus, dorsal raphe and locus coeruleus) and cortical hypometabolism have been proposed as neurobiological substrate of BPSD. Compared to with respect to the neurochemical component, the cholinergic dysfunction seems to play a major role in contributing to BPSD occurrence. This view is also supported by the findings of recent trials with cholinesterase inhibitors, showing that these drugs are effective in controlling and/or improving BPSD, independent on effects on cognitive dysfunction. On the site of psychotropic drugs, atypical or novel antipsychotics represent the reference drugs for treating BPSD, whereas classic antipsychotic drugs for their profile and the potential side effects should be avoided.

Alzheimer Disease↗

PubMed2005

Treatment of Alzheimer's disease: from pharmacology to a better understanding of disease pathophysiology.

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients and is expected to increase greatly in prevalence in the next future. It is characterized by the development of senile plaques and neurofibrillary tangles, which are associated with neuronal loss affecting to a greater extent cholinergic neurons. A cascade of pathophysiological events is triggered in AD that ultimately involves common cellular signalling pathways and leads to cellular and neural networks dysfunction, failure of neurotransmission, cell death and a common clinical outcome. The process is asynchronous and viable neurons remain an important target for therapeutic intervention at each stage of disease evolution. At present symptomatic drugs inhibiting the degradation of acetylcholine within synapses and more recently glutamate receptor antagonists represent the mainstay of therapy. However, interventions able to halt or slow disease progression (i.e., disease-modifying agents) are necessary. Although much progress has been made in this area, there are currently no clinically approved interventions for AD classed as disease modifying or neuroprotective. This paper reviews the main symptomatic strategies available for treating AD and future strategies for improving our therapeutic approach to AD.

Acetylcholine↗

PubMed2005

Diagnosing prodromal Alzheimer's disease: role of CSF biochemical markers.

Mild cognitive impairment (MCI) is an aetiologically heterogeneous syndrome. A correct prediction of MCI conversion to Alzheimer's disease (AD) represents a primary goal in routine clinical practice. Since the presence of pathological levels in >or=2 cerebrospinal fluid (CSF) biomarkers; amyloid protein (Abeta42), total tau (h-tau) and phospho-tau (p-tau) seems to reliably identifying MCI subjects converting to AD, we report our experience in a routine clinical setting. In the period from January 2001 to June 2003, 273 consecutive patients referred to our Memory Clinic for diagnostic assessment of cognitive impairment. Of them, 180 underwent a complete diagnostic evaluation including CSF dosage of fragment 1-42 of amyloid protein, total tau and phospho-tau (ELISA Method, Innogenetics, Gent, Belgium), after vascular or other secondary causes of dementia could be excluded. At baseline, 38% of the MCI subjects (20/55) showed pathological levels in >or=2 CSF biomarkers. After 1 year, 11 MCI patients converted to dementia, 33 remained stable, 11 showed a further progression of cognitive impairment still not fulfilling the diagnostic criteria for dementia. Of the 11 converters, 10 showed >or=2 pathological values CSF biomarkers and in all of them, p-tau was high. On the contrary, 29 out of 33 stable MCI (88%) showed no or one pathological CSF value. We confirm that pathological levels in >or=2 CSF biomarkers reliably predict MCI conversion to AD and correctly identify the stable form of MCI.

Alzheimer Disease↗

PubMed2005

Outcome in patients with stroke associated with internal carotid artery occlusion.

BACKGROUND: The clinical outcome in patients with stroke associated with internal carotid artery (ICA) occlusion is poor, although a minority may recover without dependency. The purposes of this study were (1) to assess the predictive factors of adverse outcome in patients with stroke associated with an occlusion of the ICA and (2) to evaluate the rate of spontaneous recanalization of an occluded ICA. METHODS: A total of 177 consecutive patients with first-ever ischemic stroke associated with ICA occlusion were prospectively examined from the Perugia Stroke Registry. Mean age was 71.4 +/- 14.3 years; 53% were males. Multiple regression models were used to analyze predictors of mortality, dependency and ipsilateral stroke recurrence. RESULTS: The most probable cause of occlusion was atherosclerosis in 65%, cardioembolism in 22%, dissection in 9% and other causes in 4%. Thirty percent of the patients died within 30 days. After a mean follow-up of 420 days (range 1-1,970 days), 45% of the patients had died and 75% had died or were disabled. Another 6% of the patients had a recurrent stroke ipsilateral to the occluded carotid artery. Age was the only predictor of 30-day mortality (77.7 +/- 9.7 vs. 68.7 +/- 15.2 years; p = 0.03) and of long-term mortality or disability (p < 0.003). Hypertension (OR 0.42; 95% CI 0.17-1.00; p = 0.05) was associated with a better outcome within 30 days from stroke onset. Previous ipsilateral transient ischemic attack (OR 0.24; 95% CI 0.06-0.89; p = 0.03) and hyperlipidemia (OR 0.38; 95% CI 0.15-0.99; p = 0.049) were predictors of a better outcome with respect to long-term mortality or disability. No predictors of ipsilateral stroke recurrence were found. One hundred and five out of 177 patients had adequate follow-up ultrasound data. After a mean follow-up of 1.8 years, 10 patients had recanalization of the occluded ICA (2/71 atherosclerosis, 3/19 cardioembolism and 5/15 dissection). CONCLUSIONS: After a mean follow-up of 1.2 years, 45% of the patients with stroke associated with ICA occlusion had died, while 75% had died or were functionally dependent. The presence of either previous ipsilateral transient ischemic attack, hypertension or hyperlipidemia was associated with a favorable outcome. Recanalization of an occluded ICA occurred in a minority of patients and it was associated with cardioembolism and with arterial dissection.

Aged↗

PubMed2004

Dysphagia following Stroke.

BACKGROUND: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. METHODS: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. RESULTS: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). CONCLUSIONS: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.

Aged↗

PubMedDate not supplied

Risk factors and stroke subtypes: results of five consecutive years of the Perugia Stroke Registry.

To understand the etiopathogenetic mechanisms of stroke and to target prevention, we need to know how risk factors differ among etiological subtypes. Our aims were to determine the different profile of risk factors for ischemic and hemorrhagic stroke subtypes in our cohort from the Perugia Hospital-Based Stroke Registry. We analyzed the characteristics and the different risk factors of 2,395 first-ever consecutive stroke patients admitted to the Perugia Hospitals in the period between January 1, 1998 and December 31, 2002. The prevalence of cerebrovascular risk factors in each stroke subtype was analyzed independently and compared with other subtypes of stroke pooled together by means of univariate analysis and logistic regression models. Hypertension occurred in 61% of patients; familial history of stroke in 41.6%; vascular disease in 27.2%; embolic heart disease in 22.3%; cigarette smoking in 21.6%. Different potentially modifiable risk factors profiles were identified for each ischemic subtype of stroke, while in hemorrhagic lobar stroke subtypes, only male gender was an independent risk factor.

Adult↗

PubMedDate not supplied

First-ever stroke and outcome in patients admitted to Perugia Stroke Unit: predictors for death, dependency, and recurrence of stroke within the first three months.

Predictors of poor outcome after first-ever stroke within 3 months in consecutive patients admitted to our Stroke Unit were defined. Factors included age, sex, risk factors, occurrence of transient ischemic attacks, extension of cerebral infarction, presumed cause of stroke, clinical findings, and demographic characteristics. Multiple regression models were used to analyze predictors of mortality, dependency and stroke recurrence. A total of 435 patients with first-ever stroke were included. Of these, 358 patients had ischemic stroke and 77 hemorrhagic stroke. Three-month mortality rate was 20.5%. After the same period, 24.6% of survivors were dependent (mRS > or = 3) and 5.0% of patients had recurrent stroke. Age, the presence of atrial fibrillation, impaired consciousness on admission, and stroke severity were related to mortality. The presence of stroke due to an undetermined cause or small vessel disease was associated with lower mortality. Partial anterior circulation syndrome or lacunar syndrome were both related to better outcome. The best predictors for dependency after 3 months were age and stroke severity. The only variable identified as the best predictor for recurrence was the presence of diabetes mellitus.

Age Factors↗

PubMedDate not supplied

Arterial hypertension and stroke prevention: an update.

High blood pressure (BP) is the most important modifiable risk factor for stroke and other vascular diseases. Evidence from randomized controlled trials supports the use of antihypertensive drugs to lower blood pressure for stroke prevention. There is some evidence that specific classes of antihypertensive drugs have different effects and/or their pharmacological actions differ in patient subgroups. This review evaluates the development of antihypertensive therapies and the latest studies of arterial hypertension and stroke prevention: HOPE trial (ramipril versus placebo), ALLHAT trial (CCB or/ and Angiotensin-Conventing enzyme Inhibitors (ACE-Is) versus diuretic), LIFE trial (losartan versus atenolol), and PROGRESS trial (perindopril or/and indapamide versus placebo). Despite the results of these relevant clinical trails, some aspects still remain unresolved. Future clinical trials on hypertension and stroke prevention should answer the following questions: Does lowering BP reduce stroke risk due to specific drug effect or class effect? Are angiotensin II receptor blockers (ARBs) better than ACE-Is? Should ACE-Is and ARBs be considered routinely for either high-risk stroke patients or patients with history of stroke or transient ischemic attack, irrespective of blood pressure? What is the role of lifestyle in BP control?

Antihypertensive Agents↗

PubMedDate not supplied

Efficacy of thrombolytic (rt-PA) therapy in old stroke patients: the Perugia Stroke Unit experience.

The use of intravenous recombinant tissue plasminogen activator (rt-PA) administered within 3 hrs from symptom onset is beneficial in selected patients independent of age; although oldest patients (> or = 80 years) are excluded a priori. We report an experience relative to rt-PA treatment in the oldest patients including outcome at 3 months. Data were from the hospital-based Perugia Stroke Registry. Seventy-two consecutive acute stroke patients, fulfilling NINDS and EUSI-criteria were treated with rt-PA of these 23 patients (30.5%) were > or = 80 years. The median and mean age were, respectively, 72.5 and 71.1 +/- 12.7 years (range 35-94). The proportion of favorable outcome at 3-months did not differ between groups (55% elderly versus 51.1% of younger patients). Proportions of unfavorable outcome and death from baseline were similar in both groups of patients. Age did not influence prognosis in patients treated with rt-PA. The oldest stroke patients should not be excluded from rt-PA treatment on the basis of age per se.

Adult↗

PubMedDate not supplied

Characteristics of delayed admission to stroke unit.

Early admission to stroke unit (SU) and factors that may cause admission delay represent relevant issues to obtain an optimal management of acute stroke. This study was aimed at recording timing from clinical onset to admission to our SU and to identify the reasons for delay. We prospectively examined acute stroke patients consecutively admitted to the Perugia SU. Baseline characteristics of stroke patients, stroke type and etiology, time from symptom onset to arrival in the SU were obtained from the Hospital-Based Perugia Stroke Registry. 60.8% of 2,213 consecutive stroke patients admitted to the SU arrived within 6 hrs and 39.2% after 6 hrs. Underestimation of symptoms was the cause of delay in 48.7% of cases. Younger age, especially for females, ischemic stroke, mild and/or unspecific symptoms and the underestimation of symptoms seem to be the main reasons for delayed arrival in the SU. To increase the proportion of stroke patients arriving in the SU within 3 hr of symptom onset, it is necessary to improve public and general practitioner awareness of stroke through educational programs.

Adult↗

PubMedDate not supplied

Multimodal use of computed tomography in early acute stroke, part 1.

Brain Computed tomography (CT) scan has been used in the past to exclude a hemorrhagic stroke, to determine a possible cause of the stroke patient symptoms, and to demonstrate a stabilized area of hypoperfusional flow. Several results from CT scan studies suggested that we could have new information on prognosis and outcome, localization, and risk of infarction. In this view, CT scan in acute stroke may contribute, using objective measures, to evaluate the inclusion in clinical and therapeutical trials, such as thrombolytic therapy. The lack of consensus among clinicians does not allow a secure and definitive system of CT scan evaluation. Besides its common uses, more recently brain CT scan provides new techniques utilizing advanced algorithms of reconstruction, with promising properties not yet completely verified, to highlight more aspects of acute stroke in the early phase. Despite this limitation, progress on neuroradiological techniques reinforces the concept that brain CT scan remains the key of studies, as well as of validation and routine treatment in terms of feasibility, low cost, and widely availability.

Acute Disease↗

PubMedDate not supplied

The Perugia hospital-based Stroke Registry: report of the 2nd year.

This study reports the characteristics of stroke patients admitted to our hospital in the period Jan 1st, 1998-Dec 31st 1999. Seven hundred and ninety seven consecutive subjects (412 males; mean age 71 +/- 13 years) with a first-ever stroke were registered. Two-thirds of patients (65%) were admitted to the Stroke Unit (SU). The remaining part was managed in six general medicine wards (GM) or other services [neurosurgery and intensive care units (ICU+ NS)]. Ischemic stroke occurred in 534 subjects (67%). The high prevalence (30.1%) of haemorrhages can be partly explained by the presence of specialized neurosurgical services. Athero-thrombotic infarctions occurred in 21.7% of patients, lacunar in 24.7%, cardioembolic in 18.1%, other determined in 6.1%, and other undetermined in 27.5%. Overall hospital mortality was 10%. In cerebral hemorrhage mortality was 18% (44/240) vs. 6.3% (32/534) in ischemic stroke (p < 0.05). The distribution of stroke types and mortality was similar to other previous reports.

Adult↗