Clinical pharmacology and vascular risk.

Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence. Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk. These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency. In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management. The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease. This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real evidence of cerebrovascular effect and drug use and abuse so as to identify a new groups of "modifiable" risk factors.

Prior use of antithrombotic agents and neurological functional outcome at discharge in patients with ischemic stroke.

BACKGROUND: Studies in experimental animals have suggested that antithrombotic agents may have a neuroprotective effect after an ischemic injury. The aim of this study was to analyze the effect of prior use of antithrombotic agents (antiplatelets or anticoagulants) on neurological functional outcome in patients with acute ischemic stroke. SUBJECTS AND METHODS: Consecutive patients included in the Perugia Stroke Registry were considered for this analysis. Neurological functional outcome was evaluated at discharge using the modified Rankin Scale (mRS >or= 3 disabling stroke). RESULTS: Of the 1921 patients included in the analysis (mean age 76.3 +/- 12.5 years; 53% males), 662 (34.5%) were on antithrombotic treatment (581 antiplatelets, 71 anticoagulants and 10 antiplatelets associated with anticoagulants). One hundred and twenty-two patients (6.4%) died in hospital; at discharge 712 patients (37.1%) were disabled and 1,087 patients (56.6%) were non-disabled. Fifty-four (44.3%) of the deceased patients and 270 (37.9%) of disabled patients were on antithrombotic treatment, while 338 (31.1%) non-disabled patients were taking antithrombotic agents. From multivariate analysis, age and stroke severity were associated with an adverse outcome. Male gender, dyslipidemia, stroke due to small vessel disease and no history of previous stroke were associated with an improved outcome, while no correlation was found between prior use of antithrombotic agents and outcome (mortality odds ratio; OR = 1.32, 95% confidence interval; CI 0.85-2.04; P = 0.20, mortality or disability OR = 0.95, 95% CI 0.72-1.25; P = 0.80). CONCLUSION: Prior use of antithrombotic agents does not improve the functional outcome in patients with acute ischemic stroke.

Secondary prevention of cardioembolic stroke: oldest and newest promises.

Atrial fibrillation (AF) is the most common cause of cardioembolism. An update on secondary prevention strategies used to protect from the risk of stroke AF patients is presented. The main line of actions of stroke prevention in AF are antithrombotics (anticoagulant or antiplatelet), antiarrhythmics (for rate control and sinus rhythm restore), mechanical means (for occlusion of the left atrial appendage or protection of the internal carotid artery from emboli). Classic pharmacological prevention with K vitamin Kantagonists such as warfarin may be overcome by direct thrombin inhibitors like ximelagatran and melagatran. New ablation technologies promise to cure, at least a part of Nonvalvolae AF in the community, restoring sinus rhythm. Recent achievements on endovascular procedures deploying carotid artery implants provide an opportunity to divert emboli to nonhazardous locations, whereas cardiac devices can seal left atrial appendages and avoid risk of clot migration in the blood stream. In the next decade, the challenge will be to understand competitiveness between old and new drugs with endovascular implants.

Educational approach on stroke training in Europe.

According to the European Stroke Initiative (EUSI), stroke care is best delivered within a stroke unit by a specialized multidisciplinary stroke team led by stroke specialists. At present, there is no guideline or consensus regarding training requirements or clinical standards that stroke specialists should achieve. It is envisaged that stroke specialists in training would need to acquire adequate knowledge and competency across three major areas of stroke care: acute stroke, stroke rehabilitation, and stroke prevention. With an EUSI document, the European Association of Young Neurologists and Trainees Stroke Subspeciality Group aims to promote discussion on the many aspects of stroke training and the requirements to be a stroke specialist in the European community. The ultimate purpose is to agree on common standards to promote good clinical care and effective stroke prevention across Europe. In the future, this may be translated into better patient outcome and a reduction in the global burden of this condition.

Early admission to stroke unit influences clinical outcome.

An improvement in patient arrival time to stroke unit (SU) is recommended, since earlier stroke management seems to improve 'per se' functional outcome. The objective of this study was to determine if early admission influences the outcome, reduces disability and mortality at discharge and three months later independent of tlirombolytic treatment. Consecutive acute stroke patients admitted to SU between January 1st 2000 and December 31st 2003 were studied in order to analyze the actual role of acute management independent specific pharmacological treatment, we excluded subjects who underwent rt-PA. 35.8% of 2,041 consecutive stroke patients arrived within 3 hours; 62.4% within 6 hours; 37.6% arrived later. Approximately 80% of the <6 hour patients presented a National Institutes of Health Stroke Scale (NIHSS) >4 and modified Rankin Scale (mRS) score >2 in comparison with 60% of the >6 hour patients. In hospital (8.7%) and three-month (7.3%) mortality in <3 hour patients were not significantly different from what observed in >3 hour patients (6.8% and 6.1% respectively) while functional outcome after three months was better in <3 hour patients (NIHSS: 34.6 vs 15.2; mRS: 32.9% vs 16.8%). Old age, history of TIA, cardioembolic etiology, severity of neurological deficit and hemorrhagic stroke type all led to earlier arrival time. Admission within 3 hours 'per se' improves outcome and reduced disability at three months.

Isolated monoparesis following stroke.

BACKGROUND: Some investigators have stated that monoparesis is almost never the result of a lacunar infarct or cerebral haemorrhage. OBJECTIVE: To describe the topography and aetiology in a consecutive population where first ever stroke was manifested by isolated monoparesis. METHODS: Patients with motor paresis of only one limb were included consecutively in the study. A neuroradiologist determined stroke location, while a neurologist reviewed the clinical records to assign stroke subtype. Both physicians worked blind to each other's findings. RESULTS: 51 of 2003 patients (2.5%) had isolated monoparesis, and of these 39 (76.5%) were ischaemic strokes and 12 (23.5%) were haemorrhagic. Cardioembolism was the cause of stroke in 15.7%, atherosclerosis in 9.8%, and small artery disease in 39.2%. Most of the haemorrhages were in the thalamic-capsular region (5/12). Most of the ischaemic lesions were in the deep territory of the middle cerebral artery, the corona radiate, or the centrum semiovale (20/39); 16 of 39 were in the cortical territories or the watershed region. CONCLUSIONS: Isolated monoparesis is a rare symptom in stroke patients and is often caused by small artery disease or a small haemorrhage.

Atrial fibrillation in patients with first-ever stroke: frequency, antithrombotic treatment before the event and effect on clinical outcome.

BACKGROUND AND PURPOSES: Atrial fibrillation (AF) is an independent risk factor for stroke. The aims of this study were to assess: (i) the frequency of known or unknown AF in patients admitted to the hospital for a first-ever ischemic stroke and whether AF is associated with an adverse outcome at discharge (death or disability); (ii) the rates and determinants for the use of antithrombotic agents before stroke in patients with known AF and the adherence to the current treatment guidelines; and (iii) whether the lack of adherence to the current guidelines is associated with adverse outcome at discharge. METHODS: Consecutive patients with acute first-ever stroke admitted to an individual Stroke Unit between January 2000 to December 2003, were included in the study. Twelve-lead electrocardiogram (ECG) was performed in all patients on admission. Functional outcome was measured at discharge according to modified Rankin Score. RESULTS: A total of 1549 patients were included in the study: 238 patients (15.4%) were known to have AF and 76 (4.9%) were diagnosed with AF (unknown) on ECG performed on admission. At discharge 91 patients (5.9%) had died and 605 patients (39.0%) had died or were functionally dependent. Multivariate analysis showed that AF on admission was correlated with mortality or disability (OR = 1.58, 95% CI 1.09-2.30, P = 0.015). Before stroke, 124 out of 238 patients with known AF (52.1%) were not on antithrombotic therapy, 83 (34.9%) were receiving antiplatelet and 31 (13.0%) anticoagulant treatment. Previous transient ischemic attack, history of ischemic heart disease and hyperlipidemia were associated with the use of antithrombotic therapy. Only 24 out of 114 patients on antithrombotic treatment on admission were adequately treated according to the current guidelines. Of the adequately treated patients, 41.7% died or were disabled at discharge respect to 52.3% of the patients non-adequately treated (RR = 0.80, 95% CI 0.48-1.30). CONCLUSIONS: AF (on history or new diagnosis) was present in 20.3% of the patients with first-ever stroke admitted to a Stroke Unit and it was associated with increased mortality or disability. Only 10% of patients with known AF were previously receiving an adequate antithrombotic treatment according to current guidelines.

Neurovascular territory involved in different etiological subtypes of ischemic stroke in the Perugia Stroke Registry.

UNLABELLED: We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first-ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1,719 patients were evaluated: 1,284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). IN CONCLUSION: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two-thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa.

Normal pressure hydrocephalus and basilar artery aneurysm. Case report and pathogenetic consideration.

The authors describe the case of a 60-year-old patient with basilar artery aneurysm who in time developed normal pressure hydrocephalus (NPH). Clinical examinations and laboratory tests did not reveal other data from which the pathology could be attributed to causes other than the vascular malformation already considered. The mechanical obstruction exerted by the aneurysm lodged on the floor of the third ventricle represents, according to the authors, the physiopathogenetic mechanism by which a temporal delay is developed between the endoventricular pulsation and that of the cerebral veins so as to produce a precise pulsatile gradient in a centrifugal direction to allow the formation of an active hydrocephalus proportional to the entity of cerebrospinal fluid (CSF) pulse.

Valproate-induced epileptic tonic status.

We observed a young patient with slight mental retardation, suffering from drug-resistant tonic-clonic seizures, who presented a status epilepticus (SE), in two separate periods when valproic acid (VPA) was added to the phenobarbital (PB) already being used in the patient's therapy. The VPA-induced SE was characterized by normal plasma levels of antiepileptic drugs (AEDs), normal ammonemia and normal liver function. The case we studied represents the first report on a VPA-induced SE. Furthermore the case confirms that VPA, as well as causing encephalopathy secondary to hyperammonemia, may also provoke a primary involvement of the central nervous system (CNS), specially when used in young epileptic, mentally retarded subjects. In an attempt to explain the paradoxical effect of VPA we hypothesise that the SE could be due to an increase in excitatory activity producing a consequent epileptogenic effect in those subjects with a predisposition for toxic reaction to VPA therapy due to congenital anomalies of neural networks.