Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Follow-Up by Transcranial Doppler After Rupture of a Giant Intracranial Aneurysm.

Giant intracranial aneurysms (GIA) are rare and manifest primarily through subarachnoid hemorrhage (SAH), cerebral ischemia, or progressive symptoms of mass effect. Transcranial Doppler (TCD) can be used to monitor cerebral vasospasm after treatment of intracranial aneurysm allowing the adjustment of therapeutics and avoiding complications. The authors present a clinical case of a patient with a ruptured intracranial giant aneurysm in which TCD was essential to monitor vasospasm and intracranial hypertension (IH). A 53-year-old male was admitted due to a sudden headache and impaired consciousness, left hemiparesis, and dysarthria. Cerebral CT scan and CT angiography at admission showed a giant aneurysm of the right middle cerebral artery (MCA) with extensive and diffuse intraventricular SAH of Fisher grade IV and Hunt and Hess grade 4. Clipping, placement of an intracranial pressure sensor, and external ventricular drain (EVD) were performed on the same day, with difficulty in preserving the M2 branch and complicated by postoperative extensive right MCA ischemia. On day three of hospitalization, TCD revealed an increased pulsatility index (>1.5) with clinical deterioration leading to re-intervention for a decompressive craniectomy. On day six, a TCD follow-up was performed to monitor blood flow complications, and particularly vasospasm, showing a severe increase in middle blood flow velocity (MBFV) in the right MCA of 205 cm/s and Lindegaard Index > 6. Daily surveillance by TCD was maintained to guide clinical management since the attempt to withdraw the EVD led to clinical deterioration with subsequent worsening of vasospasm. Improvement occurred after surgery as ventriculoperitoneal shunt insertion was performed. TCD had a major role in the clinical orientation of SAH as well as in intracranial pressure management and was decisive to establish long-term treatment.

European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion.

Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.

Neurological complications of cardiomyopathies.

There is a multifaceted relationship between the cardiomyopathies and a wide spectrum of neurological disorders. Severe acute neurological events, such as a status epilepticus and aneurysmal subarachnoid hemorrhage, may result in an acute cardiomyopathy the likes of Takotsubo cardiomyopathy. Conversely, the cardiomyopathies may result in a wide array of neurological disorders. Diagnosis of a cardiomyopathy may have already been established at the time of the index neurological event, or the neurological event may have prompted subsequent cardiac investigations, which ultimately lead to the diagnosis of a cardiomyopathy. The cardiomyopathies belong to one of the many phenotypes of complex genetic diseases or syndromes, which may also involve the central or peripheral nervous systems. A number of exogenous agents or risk factors such as diphtheria, alcohol, and several viruses may result in secondary cardiomyopathies accompanied by several neurological manifestations. A variety of neuromuscular disorders, such as myotonic dystrophy or amyloidosis, may demonstrate cardiac involvement during their clinical course. Furthermore, a number of genetic cardiomyopathies phenotypically incorporate during their clinical evolution, a gamut of neurological manifestations, usually neuromuscular in nature. Likewise, neurological complications may be the result of diagnostic procedures or medications for the cardiomyopathies and vice versa. Neurological manifestations of the cardiomyopathies are broad and include, among others, transient ischemic attacks, ischemic strokes, intracranial hemorrhages, syncope, muscle weakness and atrophy, myotonia, cramps, ataxia, seizures, intellectual developmental disorder, cognitive impairment, dementia, oculomotor palsies, deafness, retinal involvement, and headaches.

Mitochondrial Reversible Changes Determine Diastolic Function Adaptations During Myocardial (Reverse) Remodeling.

BACKGROUND: Often, pressure overload-induced myocardial remodeling does not undergo complete reverse remodeling after decreasing afterload. Recently, mitochondrial abnormalities and oxidative stress have been successively implicated in the pathogenesis of several chronic pressure overload cardiac diseases. Therefore, we aim to clarify the myocardial energetic dysregulation in (reverse) remodeling, mainly focusing on the mitochondria. METHODS: Thirty-five Wistar Han male rats randomly underwent sham or ascending (supravalvular) aortic banding procedure. Echocardiography revealed that banding induced concentric hypertrophy and diastolic dysfunction (early diastolic transmitral flow velocity to peak early-diastolic annular velocity ratio, E/E': sham, 13.6±2.1, banding, 18.5±4.1, P=0.014) accompanied by increased oxidative stress (dihydroethidium fluorescence: sham, 1.6×108±6.1×107, banding, 2.6×108±4.5×107, P<0.001) and augmented mitochondrial function. After 8 to 9 weeks, half of the banding animals underwent overload relief by an aortic debanding surgery (n=10). RESULTS: Two weeks later, hypertrophy decreased with the decline of oxidative stress (dihydroethidium fluorescence: banding, 2.6×108±4.5×107, debanding, 1.96×108±6.8×107, P<0.001) and diastolic dysfunction improved simultaneously (E/E': banding, 18.5±4.1, debanding, 15.1±1.8, P=0.029). The reduction of energetic demands imposed by overload relief allowed the mitochondria to reduce its activity and myocardial levels of phosphocreatine, phosphocreatine/ATP, and ATP/ADP to normalize in debanding towards sham values (phosphocreatine: sham, 38.4±7.4, debanding, 35.6±8.7, P=0.71; phosphocreatine/ATP: sham, 1.22±0.23 debanding, 1.11±0.24, P=0.59; ATP/ADP: sham, 6.2±0.9, debanding, 5.6±1.6, P=0.66). Despite the decreased mitochondrial area, complex III and V expression increased in debanding compared with sham or banding. Autophagy and mitophagy-related markers increased in banding and remained higher in debanding rats. CONCLUSIONS: During compensatory and maladaptive hypertrophy, mitochondria become more active. However, as the disease progresses, the myocardial energetic demands increase and the myocardium becomes energy deficient. During reverse remodeling, the concomitant attenuation of cardiac hypertrophy and oxidative stress allowed myocardial energetics, left ventricle hypertrophy, and diastolic dysfunction to recover. Autophagy and mitophagy are probably involved in the myocardial adaptation to overload and to unload. We conclude that these mitochondrial reversible changes underlie diastolic function adaptations during myocardial (reverse) remodeling.

Neurological Complications of Infective Endocarditis.

PURPOSE OF REVIEW: The purpose of this narrative review and update is to summarize the current knowledge and provide recent advances on the neurologic complications of infective endocarditis. RECENT FINDINGS: Neurological complications occur in about one-fourth of patients with infective endocarditis. Brain MRI represents a major tool for the identification of asymptomatic lesions, which occur in most of the patients with infective endocarditis. The usefulness of systematic brain imaging and the preferred treatment of patients with infective endocarditis and silent brain lesions remains uncertain. The basis of treatment of infective endocarditis is early antimicrobial therapy. In stroke due to infective endocarditis, anticoagulation and thrombolysis should be avoided. Endovascular treatment can be useful for both acute septic emboli and mycotic aneurysms, but evidence is still limited. In patients with neurological complications, cardiac surgery can be safely performed early, if indicated. The optimal management of a patients with neurological complications of infective endocarditis needs an individualized case discussion and the participation of a multidisciplinary team including neurologists, cardiologists, cardiothoracic surgeons, neuroradiologists, neurosurgeons, and infectious disease specialists.

Neurological Complications of Cardiac Tumors.

PURPOSE OF REVIEW: This article reviews recent literature regarding the neurological manifestations of cardiac tumors, including diagnosis, pathophysiology, and treatment. RECENT FINDINGS: Clinical cases of patients with acute ischemic stroke due to cardiac tumors who were treated with intravenous alteplase show a favorable safety profile. Mechanical thrombectomy seems to be a reasonable treatment alternative for these patients, when there is a large vessel occlusion. Histopathology analysis of mechanical thrombectomy specimens may allow the diagnosis of a cardiac tumor. Prolonged time interval between stroke and tumor excision surgery is significantly associated with stroke recurrence. Myxomatous aneurysms are a late complication of cardiac myxomas, which commonly demand imaging follow-up after excision of the primary tumor. Aneurysms are more frequent in patients who present with other embolic complications. Conservative treatment of myxomatous aneurysms is a reasonable strategy, as the majority of aneurysms remain stable over many years. Spontaneous regression of these formations has been documented after excision of the primary tumor. Other complications recently described include acute psychosis and mononeuropathy multiplex. Cardiac tumors are rare. There are mainly case reports and retrospective case series describing the neurological manifestations of cardiac tumors. Hyperacute stroke treatment seems to be safe, and mechanical thrombectomy is a reasonable treatment. A conservative approach towards myxomatous aneurysms should be considered.

Increase in the Admission of Stroke Mimics after Change in Emergency Shifts.

BACKGROUND: In 2010, changes were made to the shift pattern of neurology residents for cover in the Emergency Department at a university hospital. This resulted in a decrease in the number of emergency hours worked by neurology specialists and allowed for a natural quasi-experiment. AIM: We aimed to evaluate if changes to the number of emergency hours worked by neurology residents and specialist neurologists, (intervention) altered the number or pattern of admitted stroke mimics (SMs). METHODS: Observational retrospective study from January 2007 to December 2013. Time of intervention was set as August 2010. We used a segmented linear regression - ARIMA - to evaluate changes in the temporal pattern of admitted SMs. A statistical correlation between the number of emergency hours worked by neurology residents and the number of admitted SMs was calculated using the Pearson Correlation Coefficient. RESULTS: Of the 2,552 patients admitted to the stroke unit, 290 were SMs (11.4%). After August 2010, there was an increase in the number of admitted SMs (p = 0.003). After 2010, the most frequent SM diagnosis changed from a psychiatric condition to peripheral vertigo. A positive correlation was found between the number of hours worked primarily by neurology residents and the number of admitted SMs (Pearson correlation coefficient = 0.94; p = 0.002). CONCLUSIONS: Changes in the pattern of Emergency Department shifts were associated with an increase in the rate of admitted SMs and with a higher number of mimics with a final diagnosis of peripheral vertigo.

Amyloid-beta disrupts calcium and redox homeostasis in brain endothelial cells.

In Alzheimer's disease, the accumulation of amyloid-beta (Aß) in the brain occurs in the parenchyma and cerebrovasculature. Several evidences support that the neuronal demise is potentiated by vascular alterations in the early stages of the disease, but the mechanisms responsible for the dysfunction of brain endothelial cells that underlie these cerebrovascular changes are unknown. Using rat brain microvascular endothelial cells, we found that short-term treatment with a toxic dose of Aß1-40 inhibits the Ca(2+) refill and retention ability of the endoplasmic reticulum and enhances the mitochondrial and cytosolic response to adenosine triphosphate (ATP)-stimulated endoplasmic reticulum Ca(2+) release. Upon prolonged Aß1-40 exposure, Ca(2+) homeostasis was restored concomitantly with a decrease in the levels of proteins involved in its regulation operating at the plasma membrane, endoplasmic reticulum, and mitochondria. Along with perturbations in Ca(2+) regulation, an early increase in the levels of oxidants and a decrease in the ratio between reduced and oxidized glutathione were observed in Aß1-40-treated endothelial cells. Under these conditions, the nuclear levels of oxidative stress-related transcription factors, namely, hypoxia-inducible factor 1α and nuclear factor (erythroid-derived 2)-related factor 2, were enhanced as well as the protein levels of target genes. In conclusion, Aß1-40 affects several mechanisms involved in Ca(2+) homeostasis and impairs the redox homeostasis simultaneously with stimulation of protective stress responses in brain endothelial cells. However, the imbalance between cell death and survival pathways leads to endothelial dysfunction that in turn contributes to cerebrovascular impairment in Alzheimer's disease.

Infective endocarditis.

Infective endocarditis is a serious disease of the endocardium of the heart and cardiac valves, caused by a variety of infectious agents, ranging from streptococci to rickettsia. The proportion of cases associated with rheumatic valvulopathy and dental surgery has decreased in recent years, while endocarditis associated with intravenous drug abuse, prosthetic valves, degenerative valve disease, implanted cardiac devices, and iatrogenic or nosocomial infections has emerged. Endocarditis causes constitutional, cardiac and multiorgan symptoms and signs. The central nervous system can be affected in the form of meningitis, cerebritis, encephalopathy, seizures, brain abscess, ischemic embolic stroke, mycotic aneurysm, and subarachnoid or intracerebral hemorrhage. Stroke in endocarditis is an ominous prognostic sign. Treatment of endocarditis includes prolonged appropriate antimicrobial therapy and in selected cases, cardiac surgery. In ischemic stroke associated with infective endocarditis there is no indication to start antithrombotic drugs. In previously anticoagulated patients with an ischemic stroke, oral anticoagulants should be replaced by unfractionated heparin, while in intracranial hemorrhage, all anticoagulation should be interrupted. The majority of unruptured mycotic aneurysms can be treated by antibiotics, but for ruptured aneurysms, endovascular or neurosurgical therapy is indicated.

Neuroprotective effects of statins in an in vitro model of Alzheimer's disease.

Statins, used as cholesterol-lowering drugs, were reported to reduce the progression of Alzheimer's disease (AD). However, the molecular mechanisms underlying these findings remain to be clarified and it is not well understood whether this beneficial effect is due to simply lowering cholesterol levels. This study was aimed to investigate the neuroprotective effect of simvastatin and lovastatin, lipophilic statins that can transverse the blood brain barrier, against the toxicity triggered by the AD-associated amyloid-beta (Abeta) peptides and to analyze if such protection is cholesterol-independent. Using primary cultures of cortical neurons treated with Abeta1-40 peptide, we have demonstrated that pre-incubation with statins prevents the rise in cytosolic Ca2+ concentration and the accumulation of reactive oxygen species induced by Abeta through mechanisms independent of cholesterol reduction. The neuroprotective actions of statins were rather attributable to their ability to reduce isoprenyl intermediates levels in the cholesterol biosynthetic pathway since their effect was reversed by geranyl pyrophosphate while cholesterol addition was ineffective. Consequently, statins were shown to rescue cortical neurons from Abeta-40-induced caspase-3-dependent apoptosis. Moreover, our results revealed that simvastatin, at neuroprotective concentrations against Abeta-induced toxicity, is not able to activate Akt or ERK2, two signaling kinases with neuroprotective roles against apoptosis.