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.

Treating Post-stroke Epilepsy in a Patient With Multiple Comorbidities.

Stroke is a major cause of seizures and epilepsy in adults. Stroke severity, younger age, hemorrhagic subtype of stroke, and alcohol use have been identified as risk factors for the development of stroke-related epilepsy. Despite being a common complication in stroke survivors, current guidelines do not provide strong recommendations about the optimal treatment of post-stroke seizures. No clear guidance is given about the preferred antiseizure medications (ASMs), primary and secondary prophylaxis, and ASMs withdrawal. The management of older patients is further complicated by the presence of comorbidities, pharmacokinetic alterations, and intake of several medications. We present a case of a 77-year-old man affected by epidermolysis bullosa and diabetes mellitus, who suffered from ischemic stroke and then developed post-stroke seizures. This case shows how complex it is to manage post-stroke seizures in an older patient with multiple comorbidities.

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.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Management of Oral Anticoagulation and Antiplatelet Therapy in Post-Myocardial Infarction Patients with Acute Ischemic Stroke with and without Atrial Fibrillation.

The association between atrial fibrillation (AF), acute coronary syndrome (ACS), and stroke is a complex scenario in which the assessment of both thrombotic and hemorrhagic risk is necessary for scheduling an individually tailored therapeutic plan. Recent clinical trials investigating new antithrombotic drugs and dual and triple pathways in high-risk cardiovascular patients have revealed a new therapeutic scenario. In this paper, we review the burden of ischemic stroke (IS) in patients post-myocardial infarction with and without atrial fibrillation and the possible therapeutic strategies from a stroke point of view.

Impact of weather and pollution on the rate of cerebrovascular events in a large metropolitan area.

BACKGROUND: Despite mounting evidence, there is uncertainty on the impact of the interplay between weather and pollution features on the risk of acute cerebrovascular events (CVE). We aimed at appraising role of weather and pollution on the daily risk of CVE. METHODS: Anonymized data from a hub CVE center in a large metropolitan area were collected and analyzed according to weather (temperature, pressure, humidity, and rainfall) and pollution (carbon monoxide [CO], nitrogen dioxide [NO2], nitrogen oxides [NOX], ozone [O3], and particulate matter [PM]) on the same and the preceding days. Poisson regression and time series analyses were used to appraise the association between environmental features and daily CVE, distinguishing also several subtypes of events. RESULTS: We included a total of 2534 days, with 1363 days having ≥1 CVE, from 2012 to 2017. Average daily rate was 1.56 (95% confidence interval: 1.49; 1.63) for CVE, with other event rates ranging between 1.42 for stroke and 0.01 for ruptured intracranial aneurysm. Significant associations were found between CVE and temperature, pressure, CO, NO2, NOX, O3, and PM <10 µm (all P<0.05), whereas less stringent associations were found for humidity, rainfall, and PM <2.5 µm. Time series analysis exploring lag suggested that associations were stronger at same-day analysis (lag 0), but even environmental features predating several days or weeks were significantly associated with events. Multivariable analysis suggested that CO (point estimate 1.362 [1.011; 1.836], P=0.042) and NO2 (1.011 [1.005; 1.016], P<0.001) were the strongest independent predictors of CVE. CONCLUSIONS: Environmental features are significantly associated with CVE, even several days before the actual event. Levels of CO and NO2 can be potentially leveraged for population-level interventions to reduce the burden of CVE.

Cluster analysis of weather and pollution features and its role in predicting acute cardiac or cerebrovascular events.

BACKGROUND: Despite mounting evidence, the impact of the interplay between weather and pollution features on the risk of acute cardiac and cerebrovascular events has not been entirely appraised. The aim of this study was to perform a comprehensive cluster analysis of weather and pollution features in a large metropolitan area, and their association with acute cardiac and cerebrovascular events. METHODS: Anonymized data on acute myocardial infarction (AMI) and acute cerebrovascular events were obtained from 3 tertiary care centers from a single large metropolitan area. Weather and pollution data were obtained averaging measurements from several city measurement stations managed by the competent regional agency for enviromental protection, and from the Metereological Center of Italian Military Aviation. Unsupervised machine learning was performed with hierarchical clustering to identify specific days with distinct weather and pollution features. Clusters were then compared for rates of acute cardiac and cerebrovascular events with Poisson models. RESULTS: As expected, significant pairwise correlations were found between weather and pollution features. Building upon these correlations, hierarchical clustering, from a total of 1169 days, generated 4 separate clusters: mostly winter days with low temperatures and high ozone concentrations (cluster 1, N.=60, 5.1%), days with moderately high temperatures and low pollutants concentrations (cluster 2, N.=419, 35.8%), mostly summer and spring days with high temperatures and high ozone concentrations (cluster 3, N.=673, 57.6%), and mostly winter days with low temperatures and low ozone concentrations (cluster 4, N.=17, 1.5%). Overall cluster-wise comparisons showed significant differences in adverse cardiac and cerebrovascular events (P<0.001), as well as in cerebrovascular events (P<0.001) and strokes (P=0.001). Between-cluster comparisons showed that cluster 1 was associated with an increased risk of any event, cerebrovascular events, and strokes in comparison to cluster 2, cluster 3 and cluster 4 (all P<0.05), as well as AMI in comparison to cluster 3 (P=0.047). In addition, cluster 2 was associated with a higher risk of strokes in comparison to cluster 4 (P=0.030). Analysis adjusting for season confirmed the increased risk of any event, cerebrovascular events and strokes for cluster 1 and cluster 2. CONCLUSIONS: Unsupervised machine learning can be leveraged to identify specific days with a unique clustering of adverse weather and pollution features which are associated with an increased risk of acute cardiovascular events, especially cerebrovascular events. These findings may improve collective and individual risk prediction and prevention.

Acute Onset Focal Epilepsy Mimicking Stroke.

A wide range of acute neurological disorders may present with symptoms similar to a stroke, so-called 'stroke mimics'. Migraine aura and seizures account for the most extensive stroke mimics population. A large number of patients with a definite stroke mimics diagnosis (most commonly those with psychiatric disorders or seizures) had been treated with IV alteplase without adverse related events. We report a case of a man aged 70 years admitted to the emergency room because of acute onset of delirium and a loss of strength in the left arm (National Institutes of Health Stroke Scale {NIHSS}: 10), severe hyponatremia (127 mEq/L), and no evidence of intracranial arterial occlusion at CT scan. He was eligible for intravenous thrombolysis and, after treatment, neurological symptoms improved (NIHSS: 2). The subsequent appearance of "clonus" in the left lower limb, the persistence of hyponatremia, and the presence of electroencephalogram (EEG) abnormalities led to the clinical suspicion of focal motor-onset seizure with impaired awareness. The patient was treated successfully with anti-seizure medications (ASMs): lacosamide 200 mg IV during the acute setting care, followed by oral lacosamide 200 mg bis in die (BID). Since two other focal seizures occurred, brivaracetam 25 mg BID has been added in therapy with subsequent clinical discontinuance and EEG normalization. Two consecutive magnetic resonance imaging (MRI) examinations showed several cortical lesions restricted in high signal in diffusion-weighted imaging (DWI) which corresponding to T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintensities, but without lesions evidence in apparent diffusion coefficient (ADC) map. These radiological changes disappeared at a follow-up MRI performed 20 days after the symptoms' onset. The patient fully recovered was discharged home without developing pharmacological adverse events. In this case, MRI provided an opportunity for early identification of seizure-related alterations. Hence, we discuss how prospective MRI studies during seizures and interictal period would contribute to defining the relationship between the electroclinical characteristics and MRI alteration patterns, and therefore, the potential role of MRI in the differential diagnosis between seizures and stroke mimic.

Switch Strategy from Direct Aspiration First Pass Technique to Solumbra Improves Technical Outcome in Endovascularly Treated Stroke.

BACKGROUND: The major endovascular mechanic thrombectomy (MT) techniques are: Stent-Retriever (SR), aspiration first pass technique (ADAPT) and Solumbra (Aspiration + SR), which are interchangeable (defined as switching strategy (SS)). The purpose of this study is to report the added value of switching from ADAPT to Solumbra in unsuccessful revascularization stroke patients. METHODS: This is a retrospective, single center, pragmatic, cohort study. From December 2017 to November 2019, 935 consecutive patients were admitted to the Stroke Unit and 176/935 (18.8%) were eligible for MT. In 135/176 (76.7%) patients, ADAPT was used as the first-line strategy. SS was defined as the difference between first technique adopted and the final technique. Revascularization was evaluated with modified Thrombolysis In Cerebral Infarction (TICI) with success defined as mTICI ≥ 2b. Procedural time (PT) and time to reperfusion (TTR) were recorded. RESULTS: Stroke involved: Anterior circulation in 121/135 (89.6%) patients and posterior circulation in 14/135 (10.4%) patients. ADAPT was the most common first-line technique vs. both SR and Solumbra (135/176 (76.7%) vs. 10/176 (5.7%) vs. 31/176 (17.6%), respectively). In 28/135 (20.7%) patients, the mTICI was ≤ 2a requiring switch to Solumbra. The vessel's diameter positively predicted SS result (odd ratio (OR) 1.12, confidence of interval (CI) 95% 1.03-1.22; p = 0.006). The mean number of passes before SS was 2.0 ± 1.2. ADAPT to Solumbra improved successful revascularization by 13.3% (107/135 (79.3%) vs. 125/135 (92.6%)). PT was superior for SS comparing with ADAPT (71.1 min (CI 95% 53.2-109.0) vs. 40.0 min (CI 95% 35.0-45.2); p = 0.0004), although, TTR was similar (324.1 min (CI 95% 311.4-387.0) vs. 311.4 min (CI 95% 285.5-338.7); p = 0.23). CONCLUSION: Successful revascularization was improved by 13.3% after switching form ADAPT to Solumbra (final mTICI ≥ 2b was 92.6%). Vessel's diameter positively predicted recourse to SS.

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.

A clinical improvement of a idiopathic cervical dystonia in a patient treated with transdermal Rotigotine: a case-report.

Dystonia is the third most common movement disorder. Cervical dystonia is the most common form of dystonia, a subtype of Primary Focal Dystonia due to the phasic and/or tonic involuntary contractions of different combinations of neck muscles, generally treated with good clinical results with botulin toxin type A or B injection. The etiology of cervical dystonia is still unknown. It was recently proposed that the cervical dystonia is due to malfunctioning of the head neural integrator, that result of impairment in cerebellar, basal ganglia, or proprioceptive feedback. The hypothesis of the existence of an electrical circuit that connects the basal ganglia with the cerebellum and the proprioception feedback, participating in the neural integrator of the head, explains that the damage at any point of the network can lead to motor deficits. Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general view that they are ineffective. The results from the clinical trials and tests in mice suggest that the coactivation of D1 and D2 dopamine receptors may be an effective therapeutic strategy in some patients. These results support the assumption that dopamine receptors could be considered as targets for treating dystonia. Furthermore, a dopamine agonist-response dystonia in patients with an autosomal recessive L-amino acid decarboxylase deficiency, has been described in the scientific literature. We report a case of focal cervical dystonia successful treated with a dopamine agonist (D3>D2>D1) Rotigotine, a transdermal drug that induces a continuous dopaminergic stimulation.

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.

A clinical efficacy experience of Lacosamide on sleep quality in patients with Nocturnal Frontal Lobe Epilepsy (NFLE).

BACKGROUND: Nocturnal frontal lobe epilepsy (NFLE) is a focal epilepsy with seizures arising mainly during sleep and characterized by complex motor behavior or sustained dystonic posturing. First described in 1981, it was considered a motor disorder of sleep and was indicated as nocturnal paroxysmal dystonia (NPD). The debated on epileptic origin of this condition was demonstrated in 1990 and the term NFLE was introduced. Since then it has been demonstrated that the heterogeneous aspects of morpheic seizures were responsive to antiepileptic drugs (AED's) with sodium blocking action mechanism, especially the carbamazepine (CBZ). Aim of Work and Methods: We report a clinical experience of NFLE patients associated with sleep disorders treated with Lacosamide, AED's with a novel mechanism of action. In vitro electrophysiology studies have shown that lacosamide selectively boosts the slow inactivation of the sodium-voltage-dependent channels, resulting in a stabilization of the hypersensitive neuronal membranes. RESULTS AND CONCLUSION: On the treated patients we observed a positive clinical response to lacosamide therapy without significant side effects. In particular, the effective clinical response to the pharmacological treatment was obtained at a dose of 200 mg/day.