For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, ... more For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-...
The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories... more The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories, provides a favorable context for studying monogenic diseases associated with stroke. The Lombardia GENS project was set up to create a regional network for the diagnosis of six monogenic diseases associated with stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine, hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises 36 stroke centers and seven high-technology laboratories, performing molecular analysis. In this context, all stroke/TIA patients fulfilling clinical criteria for monogenic diseases are currently being included in an ongoing study. Demographic, clinical and family data and diagnostic criteria are collected using standardized forms. On the basis of stroke incidence in Lombardy and the reported prevalence of the diseases considered, we expect, during the course of the study, to collect datasets and DNA samples from more than 200 stroke patients suspected of having monogenic diseases. This will allow evaluation of the regional burden and better phenotype characterization of monogenic diseases associated with stroke.
Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, ... more Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear. We describe a 49-year-old woman with a CADASIL-like phenotype, carrying a novel cysteine-sparing mutation in exon 29 of the NOTCH3 gene, and discuss the possible pathogenetic role of this molecular variant. Even though atypical clinical and MRI findings make a diagnosis of CADASIL unlikely in this patient, our report nevertheless underlines the intriguing genotype-phenotype relationship in NOTCH3 mutations and the importance of functional investigation to ascertain the role of new NOTCH3 mutations in CADASIL pathogenesis.
Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part ... more Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part of the central nervous system. This presentation has been associated with heterozygous mutations in CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10. We aimed to investigate the genetic defect underlying multiple cerebral and vertebral cavernous malformations in a multigenerational Italian family. The proband is a 49-year-old man who underwent cerebral MRI in his thirties for persistent haeadache and tingling in his left arm and leg and was diagnosed with multiple supratentorial cavernous angiomas. A right frontal angioma with radiological evidence of a recent bleeding was surgically removed when he was 39 years old and he was thereafter asymptomatic. Magnetic resonance imaging revealed multiple cerebral cavernous malformations in seven members of his familily. Four subjects were asymptomatic. Other family mambers displayed heterogeneous clinical features including seizures and recurrent bra...
The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories... more The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories, provides a favorable context for studying monogenic diseases associated with stroke. The Lombardia GENS project was set up to create a regional network for the diagnosis of six monogenic diseases associated with stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine, hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises 36 stroke centers and seven high-technology laboratories, performing molecular analysis. In this context, all stroke/TIA patients fulfilling clinical criteria for monogenic diseases are currently being included in an ongoing study. Demographic, clinical and family data and diagnostic criteria are collected using standardized forms. On the basis of stroke incidence in Lombardy and the reported prevalence of the diseases considered, we expect, during the course of the study, to collect datasets and DNA samples from mor...
Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable,... more Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups...
NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is... more NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for e...
Safety and efficacy of carotid artery stenting have still to be fully established. We propose a s... more Safety and efficacy of carotid artery stenting have still to be fully established. We propose a standardized registry of carotid artery stenting in use at our hospital to evaluate whether the presence of an independent neurologist performing basal, procedural and post-procedural observation increases the accuracy of outcome assessment. We collected a cohort of patients receiving carotid stenting. An external neurologist supervised the endovascular intervention and monitored the patient&#39;s clinical conditions during procedure and follow-up time (12 months). The procedure was carried out successfully in all cases. We registered two intra-procedural strokes and two strokes within 24 h. The risk of major complications in our study was 9.1% at 30 days. Our complication rate is higher than in previous studies. These findings could be partly explained by the unemployment of distal protection devices, but also by the presence of an independent observer that might have increased the accuracy of neurological evaluation.
The pathogenesis of migraine with aura has not been fully established yet. The release of vasoact... more The pathogenesis of migraine with aura has not been fully established yet. The release of vasoactive substances and intracranial extracerebral blood vessel vasodilatation are probably related to stimulation of meningeal blood vessels through trigeminal afferents. Here, we report a 67 year old woman developing migraine with aphasia and right hemianopsia, lasting 4 days in duration. After spontaneous recovery, she experienced the same symptoms without migraine lasting for 15 h. MRI, performed during this last episode, revealed increased perfusion and leakage of contrast into subarachnoid space. In migraine with prolonged aura hyperperfusion with vasogenic edema might explain cortical function impairment and contribute to neurological deficits.
A number of mutations were described in the TTR gene. They were generally related to a variety of... more A number of mutations were described in the TTR gene. They were generally related to a variety of inherited syndromes named &amp;amp;#39;familial TTR-related amyloidoses&amp;amp;#39;. Although TTR mutations were mostly associated with familial amyloid polyneuropathy (FAP), these molecular variants were also found in patients with recurrent stroke, subarachnoidal bleeding and radiological findings of cerebral, cerebellar, cortical-subcortical infarctions and hemosiderosis. We describe a 46 y.o. man with recurrent cerebral haemorrhages carrying Asn90His variant of TTR gene. This mutation has been reported both in FAP and asymptomatic subjects raising the doubt on the possible amyloidogenetic role of this variant. The absence of mutation in the patient&amp;amp;#39;s father, who had a history of unexplained cerebral haemorrhage and the lack of symptoms and sign of cerebral bleeding in the two patient&amp;amp;#39;s sisters, carrying the same mutation, seem to support the hypothesis that His90Asn TTR mutation do not have an impact in amyloid formation. It has still to be established whether other gene variants in our patient could act synergistically with His90Asn TTR mutation in increasing the risk of CNS haemorrhages.
Journal of Neurology, Neurosurgery & Psychiatry, 2009
... 2 Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; 3 Ci... more ... 2 Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; 3 Civic Hospital of Lugano, Lugano, Switzerland. Dr A Bersano, Department of Neurological Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina ...
To date, evidence to recommend endovascular treatment in patients with intracranial stenoses is l... more To date, evidence to recommend endovascular treatment in patients with intracranial stenoses is lacking. Recently, the introduction of self-expanding stents (Wingspan Stent System) aroused considerable expectations in their employ for stroke prevention. We report a single-center experience of percutaneous transluminal angioplasty and stenting in a series of consecutive patients with intracranial stenoses and compare the safety and performance of balloon-mounted stents versus self-expanding stent systems (Wingspan). Thirty-four patients with 39 severe (&gt;70%) intracranial stenoses were treated during a 6-year period. An independent stroke neurologist collected data about intra and periprocedural complications and short-term outcome. We considered as endpoint measures (1) any 30-day stroke or death (2) any major 30-day complication and (3) procedure technical success. Technical success was achieved in all patients. No vessel dissection or ruptures were observed. The 30-day stroke/death rate was 17.9%. Five ischemic strokes in the territory of treated vessels and two intracranial hemorrhages occurred respectively within 24 h and 5 days after endovascular treatment. Three (17.6%) patients of Wingspan treated group and four (18.2%) of the patients treated with different stent systems had unfavorable outcome. Our study confirms that endovascular treatment can be performed with a high technical success rate, even though the safety of these devices has still to be demonstrated.
Epidemiological and family studies have provided evidence on the role of genetic factors in strok... more Epidemiological and family studies have provided evidence on the role of genetic factors in stroke, particularly in stroke occurring at young age. However, despite its impact, young stroke continues to be understudied. This article reviews the existing literature on the most investigated monogenic disorders (CADASIL, Fabry disease, MELAS, RVCL, COL4A1, Marfan and Ehlers-Danlos syndromes) causing stroke in young and a number of candidate genes associated with stroke occurring in patients younger than 50 years. Although our study failed in identifying strong and reliable associations between specific genes and young stroke, our detailed literature revision on the field allowed us to compile a panel of genes possibly generating a susceptibility to stroke, which could be a starting point for future research. Since stroke is a potentially preventable disease, the identification of genes associated with young stroke may promote novel prevention strategies and allow the identification of therapeutic disease targets.
Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence athero... more Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence atherogenesis not only by increasing atherosclerotic plaque stability but also by modulating endothelial function and inflammation and acting on platelet aggregation and thrombosis. Despite a strong association between increased levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) has been well proven, it not yet established whether serum LDL-C levels are related to stroke incidence. The major aim of this paper is to perform a comprehensive up-to-date review of research papers, meta-analyses and randomized controlled clinical trials reporting the effects of statins in primary and secondary stroke prevention strategies. In addition, our work provides an overview on statin chemical structure, mechanism of action and pharmacological properties, investigating also most common adverse effects and relationship between statin therapy and haemorrhagic stroke risk, in order to assess drugs safety. Although studies are heterogeneous, our analysis shows that statins reduce the risk of stroke occurrence in high risk patients and seem also to reduce stroke recurrence. Moreover, the low incidence and reversibility of adverse effects, and the unclear association with hemorrhagic events, support the safe use of these drugs.
For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, ... more For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-...
The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories... more The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories, provides a favorable context for studying monogenic diseases associated with stroke. The Lombardia GENS project was set up to create a regional network for the diagnosis of six monogenic diseases associated with stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine, hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises 36 stroke centers and seven high-technology laboratories, performing molecular analysis. In this context, all stroke/TIA patients fulfilling clinical criteria for monogenic diseases are currently being included in an ongoing study. Demographic, clinical and family data and diagnostic criteria are collected using standardized forms. On the basis of stroke incidence in Lombardy and the reported prevalence of the diseases considered, we expect, during the course of the study, to collect datasets and DNA samples from more than 200 stroke patients suspected of having monogenic diseases. This will allow evaluation of the regional burden and better phenotype characterization of monogenic diseases associated with stroke.
Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, ... more Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear. We describe a 49-year-old woman with a CADASIL-like phenotype, carrying a novel cysteine-sparing mutation in exon 29 of the NOTCH3 gene, and discuss the possible pathogenetic role of this molecular variant. Even though atypical clinical and MRI findings make a diagnosis of CADASIL unlikely in this patient, our report nevertheless underlines the intriguing genotype-phenotype relationship in NOTCH3 mutations and the importance of functional investigation to ascertain the role of new NOTCH3 mutations in CADASIL pathogenesis.
Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part ... more Cerebral cavernous malformations are relatively rare vascular disorders that may affect any part of the central nervous system. This presentation has been associated with heterozygous mutations in CCM1/KRIT1, CCM2/malcavernin and CCM3/PDCD10. We aimed to investigate the genetic defect underlying multiple cerebral and vertebral cavernous malformations in a multigenerational Italian family. The proband is a 49-year-old man who underwent cerebral MRI in his thirties for persistent haeadache and tingling in his left arm and leg and was diagnosed with multiple supratentorial cavernous angiomas. A right frontal angioma with radiological evidence of a recent bleeding was surgically removed when he was 39 years old and he was thereafter asymptomatic. Magnetic resonance imaging revealed multiple cerebral cavernous malformations in seven members of his familily. Four subjects were asymptomatic. Other family mambers displayed heterogeneous clinical features including seizures and recurrent bra...
The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories... more The Italian region of Lombardy, with its existing stroke centers and high-technology laboratories, provides a favorable context for studying monogenic diseases associated with stroke. The Lombardia GENS project was set up to create a regional network for the diagnosis of six monogenic diseases associated with stroke: CADASIL, Fabry disease, MELAS, familial and sporadic hemiplegic migraine, hereditary cerebral amyloid angiopathy and Marfan syndrome. The network comprises 36 stroke centers and seven high-technology laboratories, performing molecular analysis. In this context, all stroke/TIA patients fulfilling clinical criteria for monogenic diseases are currently being included in an ongoing study. Demographic, clinical and family data and diagnostic criteria are collected using standardized forms. On the basis of stroke incidence in Lombardy and the reported prevalence of the diseases considered, we expect, during the course of the study, to collect datasets and DNA samples from mor...
Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable,... more Epidemiological studies suggest that white matter hyperintensities (WMH) are extremely heritable, but the underlying genetic variants are largely unknown. Pathophysiological heterogeneity is known to reduce the power of genome-wide association studies (GWAS). Hypertensive and nonhypertensive individuals with WMH might have different underlying pathologies. We used GWAS data to calculate the variance in WMH volume (WMHV) explained by common single nucleotide polymorphisms (SNPs) as a measure of heritability (SNP heritability [HSNP]) and tested the hypothesis that WMH heritability differs between hypertensive and nonhypertensive individuals. WMHV was measured on MRI in the stroke-free cerebral hemisphere of 2336 ischemic stroke cases with GWAS data. After adjustment for age and intracranial volume, we determined which cardiovascular risk factors were independent predictors of WMHV. Using the genome-wide complex trait analysis tool to estimate HSNP for WMHV overall and within subgroups...
NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is... more NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16 954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for e...
Safety and efficacy of carotid artery stenting have still to be fully established. We propose a s... more Safety and efficacy of carotid artery stenting have still to be fully established. We propose a standardized registry of carotid artery stenting in use at our hospital to evaluate whether the presence of an independent neurologist performing basal, procedural and post-procedural observation increases the accuracy of outcome assessment. We collected a cohort of patients receiving carotid stenting. An external neurologist supervised the endovascular intervention and monitored the patient&#39;s clinical conditions during procedure and follow-up time (12 months). The procedure was carried out successfully in all cases. We registered two intra-procedural strokes and two strokes within 24 h. The risk of major complications in our study was 9.1% at 30 days. Our complication rate is higher than in previous studies. These findings could be partly explained by the unemployment of distal protection devices, but also by the presence of an independent observer that might have increased the accuracy of neurological evaluation.
The pathogenesis of migraine with aura has not been fully established yet. The release of vasoact... more The pathogenesis of migraine with aura has not been fully established yet. The release of vasoactive substances and intracranial extracerebral blood vessel vasodilatation are probably related to stimulation of meningeal blood vessels through trigeminal afferents. Here, we report a 67 year old woman developing migraine with aphasia and right hemianopsia, lasting 4 days in duration. After spontaneous recovery, she experienced the same symptoms without migraine lasting for 15 h. MRI, performed during this last episode, revealed increased perfusion and leakage of contrast into subarachnoid space. In migraine with prolonged aura hyperperfusion with vasogenic edema might explain cortical function impairment and contribute to neurological deficits.
A number of mutations were described in the TTR gene. They were generally related to a variety of... more A number of mutations were described in the TTR gene. They were generally related to a variety of inherited syndromes named &amp;amp;#39;familial TTR-related amyloidoses&amp;amp;#39;. Although TTR mutations were mostly associated with familial amyloid polyneuropathy (FAP), these molecular variants were also found in patients with recurrent stroke, subarachnoidal bleeding and radiological findings of cerebral, cerebellar, cortical-subcortical infarctions and hemosiderosis. We describe a 46 y.o. man with recurrent cerebral haemorrhages carrying Asn90His variant of TTR gene. This mutation has been reported both in FAP and asymptomatic subjects raising the doubt on the possible amyloidogenetic role of this variant. The absence of mutation in the patient&amp;amp;#39;s father, who had a history of unexplained cerebral haemorrhage and the lack of symptoms and sign of cerebral bleeding in the two patient&amp;amp;#39;s sisters, carrying the same mutation, seem to support the hypothesis that His90Asn TTR mutation do not have an impact in amyloid formation. It has still to be established whether other gene variants in our patient could act synergistically with His90Asn TTR mutation in increasing the risk of CNS haemorrhages.
Journal of Neurology, Neurosurgery & Psychiatry, 2009
... 2 Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; 3 Ci... more ... 2 Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; 3 Civic Hospital of Lugano, Lugano, Switzerland. Dr A Bersano, Department of Neurological Sciences, University of Milan, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina ...
To date, evidence to recommend endovascular treatment in patients with intracranial stenoses is l... more To date, evidence to recommend endovascular treatment in patients with intracranial stenoses is lacking. Recently, the introduction of self-expanding stents (Wingspan Stent System) aroused considerable expectations in their employ for stroke prevention. We report a single-center experience of percutaneous transluminal angioplasty and stenting in a series of consecutive patients with intracranial stenoses and compare the safety and performance of balloon-mounted stents versus self-expanding stent systems (Wingspan). Thirty-four patients with 39 severe (&gt;70%) intracranial stenoses were treated during a 6-year period. An independent stroke neurologist collected data about intra and periprocedural complications and short-term outcome. We considered as endpoint measures (1) any 30-day stroke or death (2) any major 30-day complication and (3) procedure technical success. Technical success was achieved in all patients. No vessel dissection or ruptures were observed. The 30-day stroke/death rate was 17.9%. Five ischemic strokes in the territory of treated vessels and two intracranial hemorrhages occurred respectively within 24 h and 5 days after endovascular treatment. Three (17.6%) patients of Wingspan treated group and four (18.2%) of the patients treated with different stent systems had unfavorable outcome. Our study confirms that endovascular treatment can be performed with a high technical success rate, even though the safety of these devices has still to be demonstrated.
Epidemiological and family studies have provided evidence on the role of genetic factors in strok... more Epidemiological and family studies have provided evidence on the role of genetic factors in stroke, particularly in stroke occurring at young age. However, despite its impact, young stroke continues to be understudied. This article reviews the existing literature on the most investigated monogenic disorders (CADASIL, Fabry disease, MELAS, RVCL, COL4A1, Marfan and Ehlers-Danlos syndromes) causing stroke in young and a number of candidate genes associated with stroke occurring in patients younger than 50 years. Although our study failed in identifying strong and reliable associations between specific genes and young stroke, our detailed literature revision on the field allowed us to compile a panel of genes possibly generating a susceptibility to stroke, which could be a starting point for future research. Since stroke is a potentially preventable disease, the identification of genes associated with young stroke may promote novel prevention strategies and allow the identification of therapeutic disease targets.
Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence athero... more Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence atherogenesis not only by increasing atherosclerotic plaque stability but also by modulating endothelial function and inflammation and acting on platelet aggregation and thrombosis. Despite a strong association between increased levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) has been well proven, it not yet established whether serum LDL-C levels are related to stroke incidence. The major aim of this paper is to perform a comprehensive up-to-date review of research papers, meta-analyses and randomized controlled clinical trials reporting the effects of statins in primary and secondary stroke prevention strategies. In addition, our work provides an overview on statin chemical structure, mechanism of action and pharmacological properties, investigating also most common adverse effects and relationship between statin therapy and haemorrhagic stroke risk, in order to assess drugs safety. Although studies are heterogeneous, our analysis shows that statins reduce the risk of stroke occurrence in high risk patients and seem also to reduce stroke recurrence. Moreover, the low incidence and reversibility of adverse effects, and the unclear association with hemorrhagic events, support the safe use of these drugs.
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