Recurrent paraneoplastic cerebral hemorrhage in lung cancer: A case report.

Cerebral hemorrhage management in a patient requiring anticoagulant therapy is a therapeutic challenge also due to the absence of guidelines that convincingly define the best therapeutic strategy. Although the occurrence of cerebral hemorrhage in a patient with anticoagulant therapy seems to make the bleeding etiology obvious, sometimes, it is better to reflect on other possible causes and set up an adequate diagnostic workup. Herein, we describe a case of a 73-year-old male patient with atrial fibrillation, mechanical heart valve, and pacemaker that experienced an ischemic minor stroke during steady anticoagulation therapy with recurrent intracerebral haemorrhages (ICHs).

The Pathophysiology of Collateral Circulation in Acute Ischemic Stroke.

Cerebral collateral circulation is a network of blood vessels which stabilizes blood flow and maintains cerebral perfusion whenever the main arteries fail to provide an adequate blood supply, as happens in ischemic stroke. These arterial networks are able to divert blood flow to hypoperfused cerebral areas. The extent of the collateral circulation determines the volume of the salvageable tissue, the so-called "penumbra". Clinically, this is associated with greater efficacy of reperfusion therapies (thrombolysis and thrombectomy) in terms of better short- and long-term functional outcomes, lower incidence of hemorrhagic transformation and of malignant oedema, and smaller cerebral infarctions. Recent advancements in brain imaging techniques (CT and MRI) allow us to study these anastomotic networks in detail and increase the likelihood of making effective therapeutic choices. In this narrative review we will investigate the pathophysiology, the clinical aspects, and the possible diagnostic and therapeutic role of collateral circulation in acute ischemic stroke.

Lipid profiles and atrial fibrillation in ischemic stroke patients treated with thrombectomy: experience from a tertiary Italian stroke hospital.

OBJECTIVES: To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS). METHODS: We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined assessed the association between lipid profile, AF and EVT in multivariate logistic regression analysis. RESULTS: Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n= 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years [IQR; 63-80 ] versus 74 years [ QR; 63-82+ HbA1c levels (median 5.8 [IQR; 5.4-6.2] versus 5.9 [ IQR; 5.4-6.4+TG/HDL ratio (median 2.40 [IQR; 1.65-3.48#43; versus[IQR; 1.73-3.64)] diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl[ IQR;139-187] versus 173 mg/dl [ IQR;148-202] P <0.001), LDL-C (105 mg/dl [ IQR; 80-133] versus 113 mg/dl [ IQR; 88-142] ; P <0.01), TG (98 mg/dl [ IQR; 76-126] versus 107 mg/dl [ IQR; 85-139] P <0.001), non-HDL-C (117 mg/dl[ IQR; 94-145] versus 127 mg/dl [ IQR; 103-154] P <0.001), HC (8.3[ mol/l [ IQR; 6-11] versus 10 µ mol/l[ IQR; 7.3-13.5] P <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19). CONCLUSION: Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve enhance the discovery of specific and tailored preventive treatments.

An uncommon case of nonconvulsive status epilepticus successfully treated with enteral Brivaracetam.

BACKGROUND AND AIM OF THE WORK: We present a case of a woman affected by nonconvulsive status epilepticus (NCSE) caused by cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA) who was successfully treated with Brivaracetam (BRV) administered via nasogastric tube (NGT). CASE PRESENTATION: An 82-years old woman was referred for increasing blood pressure, severe headache and two focal motor seizures on postoperative day four after right CEA. CT scan showed edema of the right hemisphere with a midline shift of 5 mm. The patient underwent daily Electroencephalography (EEG) monitoring which showed continuous epileptiform discharges over the right hemisphere, compatible with a diagnosis of status epilepticus. She was treated with standard antiepileptic drugs (Phenytoin, Lacosamide and Levetiracetam iv) without clinical response. A therapeutic trial with BRV 200mg administered via nasogastric tube (NGT) was tried which resulted in substantial clinical benefit. CONCLUSIONS: The administration of new antiepileptic drugs (AEDs) such as BRV may result in significant clinical improvement in refractory cases of status epilepticus. The enteral administration of AEDs via NGT should always be considered for refractory cases of status epilepticus when standard iv treatment has failed or is not possible.

Ischemic Stroke in the Very Elderly: Experience from an Italian Stroke Unit Hub Over a Period of 8 Years in the Era of Thrombectomy.

OBJECTIVE: The goal of this study is to understand how very elderly patients (VEP) after ischemic stroke are currently treated in a Stroke Unit (SU) Hub in Italy. We designed a retrospective monocentric study on patients admitted in the SU of "AO San Camillo Forlanini" over an 8-year period. MATERIAL AND METHODS: Data were collected among patients with acute ischemic stroke admitted to SU between January 2012 and December 2019. Patients were divided into three sub-groups: Adults (18-65 years); Elderly (66-85 years); and VEP (>85 years). Vascular risk factors and clinical variables as predictors of short-term clinical outcome were compared among age groups. RESULTS: A total of 1979 patients were enrolled, 254 were VEP (12.8%). The proportion of VEP showed no significant modifications during the 8-year period (11.9% in 2012-2015 and 13.7% in 2016-2019; p=0.93). The proportion of women, hypertension and atrial fibrillation was significantly higher in VEP compared to other age groups (p<0.001). The rate of VEP being treated with rt-PA increased from 2012-2015 to 2016-2019 (from 12.8% to 25.5%, p<0.001). Endovascular thrombectomy was rarely performed in VEP (1.5% of VEP). Rt-PA treatment was associated with favorable outcome for all three age groups (p<0.05). CONCLUSIONS: We showed that VEP present different vascular risk factor profiles, clinical features, and prognostic elements for short-term stroke outcome. Future studies will reveal whether we will observe an increasing trend in the use of rt-PA and endovascular thrombectomy and whether it will result in improved functional outcome for VEP.

Unsuccessful Endovascular Treatment in a Patient With Stroke Onset of Takayasu Arteritis and Positive Clinical Outcome.

Takayasu's arteritis (TA) is a chronic progressive vasculitis affecting large and medium-sized vessels, mainly in young subjects. It is most common in women with a higher prevalence in the Asian population. Stroke is a rare complication of TA, and these patients usually have a poor therapeutic response to revascularization treatments (thrombolysis and/or thrombectomy). We report a case of a male patient aged between 40 and 50 years admitted to our Emergency Department's Stroke Unit for sudden left hemiplegia, hypoesthesia, and dysarthria caused by right internal carotid artery (ICA), middle cerebral artery (MCA), and anterior cerebral artery (ACA) occlusion. He was treated with intravenous thrombolysis (r-tPA), endovascular carotid stenting, and thromboaspiration. We also revealed subclavian stenosis, vascular bruit, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) elevation; therefore, a diagnosis of TA was made. Double antiplatelet therapy (DAPT) was started. Despite the early post-procedural carotid stent occlusion, the patient was discharged with a full recovery (neurological index of stroke scale [NIHSS] = 0). Thefive5-year clinical follow-up showed no clinical neurological relapses, and no arterial restenosis was found by further carotid artery echo-Doppler. Takayasu arteritis is a rare cause of ischemic stroke in young adults; however, stroke may be the first manifestation of the disease. Guidelines concerning the role of revascularization treatment in this type of patients are unclear. In this regard, the clinical experience and the multidisciplinary approach applied in our case had a pivotal role. Such an approach would eventually advocate for standardized treatment in patients with stroke and TA.

Effect of Cardioembolic Etiology on Intravenous Thrombolysis Efficacy for Acute Ischemic Stroke.

Previous clinical studies suggest that intravenous (IV) recombinant tissue plasminogen activator (rt-PA) benefits stroke patients regardless of the underlying etiology. In this study, we assessed the possible differences in response to IV rt-PA between cardioembolic stroke and other stroke subtypes. A total of 303 consecutive stroke ischemic patients (from January 2005 to April 2014) admitted to our Stroke Unit and treated with IV rt-PA were retrospectively reviewed. All patients were classified in two groups: Cardioembolic (CE) and Non-Cardioembolic (NCE). We analyzed a total of 303 patients. Thirty patients died in the first hours after fibrinolysis and no statistically significant differences were found in two groups (14 CE vs 18 N-CE). We observed a significant differences in clinical outcome in terms of symptoms "improvement" (p< 0.01 .2) and symptoms" regression" (p<0.057 .2) even if this last result did not reach statistical significance in CE patients respect to N-CE patients. In conclusion, the intravenous fibrinolysis is more effective in CE group than in N-CE regarding symptoms "improvement" and the PFO-Stroke patients treated with fibrinolysis have better outcome than other patients and they have high rate of symptoms" regression". Moreover the main predictor of good outcomes were younger age and milder stroke severity on hospital admission.

Transient Ischemic Attack Fast-track and Long-Term Stroke Risk: Role of Diffusion-Weighted Magnetic Resonance Imaging.

BACKGROUND: Acute ischemic lesions on diffusion-weighted magnetic resonance imaging (DWI-MRI) are reliable predictors of recurrent stroke at 90 days. However, to date, limited information on transient ischemic attack (TIA) patients with positive DWI lesions for stroke risk from 1 to 5 years is available. In this study, we evaluated the role of positive DWI lesions and vascular risk factors on stroke, cardiovascular death, and mortality at 90 days (T0), 1 year (T1), and 5 years (T2). Moreover, we also evaluated the association between stroke risk and the presence of DWI lesions. METHODS: We performed an observational study on consecutive patients admitted to the emergency department of San Camillo-Forlanini Hospital, Rome, Italy, from January 2007 to November 2012. Over the study period, 4300 patients with TIA or ischemic stroke were examined by stroke specialists in an emergency room setting within 1 hour from admittance. RESULTS: In 510 of 4300 patients (11.86%), a TIA was diagnosed, and 445 patients satisfy the study inclusion criteria. For all 445 patients, the mean ABCD2 score was 4.35 ± 1.30. Using DWI-MRI, we identified acute ischemic lesions in 185 patients (41.57%). We did not observe any correlation between duration of symptoms, ABCD2 score, and positive or negative DWI lesions. Positivity for DWI was not associated with the presence of diabetes mellitus, hypertension, smoking habit, or age; however, an association with weakness was observed. We documented a time-dependent increase in the absolute risk of stroke: T0: 1.35% (95% confidence interval [CI], .81-2.8); T1: 4.78% (95% CI, 2.88-7.47); T2: 9.02% (95% CI, 4.66-5.70). We did not record any difference in stroke risk in patients with positive DWI lesions: T0: hazard ratio [HR], 1.43; 95% CI, .35-5.88; log-rank P = .60; T1: HR, 1.04; 95%CI, .42-2.61; log-rank P = .91; T2: HR, .83; 95% CI, .25-2.67; log-rank P = .86. CONCLUSIONS: This long-term follow-up study in TIA patients documents that both positive and negative DWI patients treated with fast-track had similar long-term risks of stroke.

Pulmonary arteriovenous malformation as a cause of embolic stroke: case report and review of the literature.

BACKGROUND: Pulmonary arteriovenous malformation (PAVM) is an abnormal communication between pulmonary arteries and veins responsible for right-to-left shunting that could induce the development of embolic stroke. SUMMARY: We describe an 82-year-old woman without history of respiratory or neurological diseases, who presented at our observation unit with acute onset of cerebral ischemia. Clinical, laboratory and radiological findings diagnosed a PAVM. KEY MESSAGES: Usually, endovascular procedures based on embolization or, alternatively, surgery represent the recommended treatment. However, both hormonal therapy and thrombolytic therapy can be used. In our patient, treatment with warfarin induced a remission of symptoms. This strategy should be tested in larger studies.

Endothelial dysfunction and oxidative stress in type 1 and type 2 diabetic patients without clinical macrovascular complications.

AIMS: To evaluate the relationship between oxidative stress and endothelial dysfunction (ED) in diabetic patients without clinical macrovascular complications. METHODS: In 27 type 1, 56 type 2 diabetic patients and 35 healthy controls the redox state (GSH, GSSG; enzymatic method), endothelin-1 (ET-1; ELISA) and von Willebrand factor (vWF; ELISA) plasma levels, urinary vascular endothelial growth factor (VEGF; ELISA) were measured. RESULTS: Decreased GSH levels (p<0.05, type 1 and type 2), GSH/GSSG ratio (p<0.05 type 1, p<0.001 type 2) and elevated vWF levels (p<0.001, type 1 and type 2) were observed in diabetic patients in comparison with controls. A negative correlation between GSH and vWF (p<0.02 and p<0.001, in type 1 and type 2, respectively) and GSH and BMI (p<0.02 in type 1 and type 2) was observed. ET-1 was positively correlated to age (p<0.05) and diabetes duration (p<0.03) in type 1, while vWF was correlated to systolic blood pressure (p<0.05) in type 2 diabetic patients. Urinary VEGF was higher in type 2 (p<0.05) in comparison with type 1 diabetic patients and was correlated to glycemia (p<0.05) and systolic blood pressure (p<0.05). CONCLUSIONS: These data might indicate that markers of oxidative stress and ED are altered in diabetic patients without clinical macrovascular complications.

Insulin decreases intracellular oxidative stress in patients with type 2 diabetes mellitus.

Patients affected by diabetes mellitus have oxidative stress with an impaired glutathione (GSH) redox state. The objective of this study was to determine the influence of insulin on oxidative stress, defined as a reduced intracellular GSH/GSH disulfide (GSSG) ratio and lipid peroxidation by plasma thiobarbituric acid reactive substances (TBARSs) in patients with type 2 diabetes. Two experimental interventions were used: (1) measurement of GSH/GSSG ratio after insulin incubation in erythrocytes from 10 type 2 diabetic patients, and (2) measurement of intraerythrocytic GSH/GSSG ratio and plasma TBARS in 14 type 2 diabetic patients during an in vivo hyperinsulinemic condition obtained from a euglycemic hyperinsulinemic clamp study. We confirmed that our patients underwent oxidative stress as shown by the significant difference in intracellular GSH/GSSG ratio in diabetic patients as compared to controls (13.56+/-3.84 vs 27.89+/-8.37, P<.0001). We found a significant elevation in the GSH/GSSG ratio after 2 hours of incubation with insulin in erythrocytes from diabetic patients (11.56+/-1.98 to 15.61+/-2.62, P<.001). During the clamp studies, GSH/GSSG ratio had already increased after 60 minutes and even more after 120 minutes (baseline, 15.04+/-4.19; at 60 minutes, 19.74+/-6.33; at 120 minutes, 25.33+/-11.15; P<.0001). On the contrary, no significant changes were observed in plasma TBARS (3.59+/-0.77 to 3.56+/-0.83, NS). We conclude that insulin in patients with type 2 diabetes mellitus can reduce intracellular oxidative stress through increased GSH/GSSG ratio.

Impairment of cell and plasma redox state in subjects professionally exposed to chromium.

BACKGROUND: Chromium (Cr) is widely used in chemical, tannery, building, and metal industries. More recently, it has been demonstrated that Cr induces oxidative stress in mouse brain. Nevertheless very few data exist on in vivo oxidative damage in humans exposed to Cr. METHODS: Changes in antioxidant parameters both in plasma (acid ascorbic redox state and total antioxidant capacity) and in red blood cells (glutathione (GSH) redox state) of 40 subjects (age 37.65 +/- 7.46; M/F 20/20) professionally exposed to Cr who were recruited from metal, chemistry, and building industries were evaluated. We also evaluated the levels of lipoperoxidation (thiobarbituric acid-reactive material, TBA-RM) and thiol levels in plasma to assess the extent of oxidative stress state. To evaluate Cr exposure rate, we measured urinary-chromium (U-Cr) by an electrothermic atomization-atomic absorption spectrometry (ETA-AAS) method. RESULTS: In this study, we found that Cr exposure induced a decrease both in GSH (P < 0.0005) and GSH/oxidized glutathione (GSSG) ratio (P < 0.0001) in red blood cells from workers with respect to control subjects. Furthermore, we also demonstrated a significant decrease of plasma acid ascorbic levels (45.7 +/- 14.9 vs. 53.5 +/- 16.5 micromol/L; P < 0.05) and in total plasma antioxidant capacity (1,126.3 +/- 212.2 vs. 1,266.9 +/- 207.8 micromol/L; P < 0.05) in subjects exposed to Cr. No difference was found with regard to TBA-RM and thiol levels. CONCLUSIONS: This study demonstrated that in humans, an oxidative stress occurs for Cr exposures as low as those considered safe. This oxidative stress appears to be able to affect intracellular and plasmatic antioxidant defense.

Angiotensin II inhibits endothelial cell motility through an AT1-dependent oxidant-sensitive decrement of nitric oxide availability.

OBJECTIVE: The migratory capability of vascular endothelial cells plays a pivotal role in the maintenance of vessel wall integrity and is stimulated by nitric oxide (NO). Angiotensin II increases NAD(P)H oxidase activity in endothelial cells, thereby promoting reactive oxygen species (ROS) generation. Because ROS can both reduce NO synthase activity and increase NO breakdown, thus impairing NO availability in endothelial cells, we evaluated the effect of angiotensin II on human vascular endothelial cell (HUVEC) motility. METHODS AND RESULTS: Angiotensin II dose- and time-dependently reduced HUVEC migration. Besides inhibiting HUVEC motility, angiotensin II altered intracellular glutathione redox status. The generation of ROS by cultured HUVECs was significantly increased by angiotensin II. Furthermore, angiotensin II reduced NO metabolite concentrations in culture media. The angiotensin II type 1 receptor antagonist candesartan cilexetil attenuated the inhibitory action exerted by angiotensin II on HUVEC motility, reversed the angiotensin II-induced increase in intracellular oxidative stress, and restored NO availability. Similar effects were exerted by the flavonoid inhibitor diphenylene iodinium and the antioxidant agent N-acetyl-L-cysteine. CONCLUSIONS: All together, our data demonstrate that angiotensin II inhibits HUVEC motility by reducing NO availability. Such reduction is due to an angiotensin II type 1 receptor-dependent increment in intracellular ROS generation.