Intraluminal carotid thrombus leading to postpartum stroke: a case study.

BACKGROUND: Intraluminal non-occlusive thrombus (ILT) is a rare cause of ischemic stroke. Although in most cases ILT is associated with arterial wall disorders, it has also been documented in patients with thrombophilic conditions. CASE REPORT: We present a case of carotid ILT in a 38-year-old puerperal woman with pregnancy-induced hypercoagulability. Following in vitro fertilization pregnancy, she experienced acute left-sided weakness 9 days after delivery. CT angiography revealed an intraluminal filling defect in the right carotid bulb, suggestive of a thrombus, along with ipsilateral MCA sub-occlusion. Mechanical thrombectomy was performed, achieving complete vessel recanalization without any endovascular intervention on the carotid ILT. Comprehensive evaluation excluded any underlying carotid vessel wall disease (such as atherosclerosis, inflammatory diseases, arterial dissection, focal dysplasia), inherited or acquired thrombophilia, and the sole prothrombotic risk factor identified was the puerperium. Histological thrombus analysis showed fibrin/platelet-rich material with significant macrophage infiltration (consistent with an intermediate/organized thrombus, suggesting potential embolization from a pre-existing carotid ILT). Anti-thrombotic treatment (acetylsalicylic acid 100 mg and enoxaparin 6000 UI) resulted in complete thrombus resolution at follow-up. CONCLUSION: ILT should be considered a potential case of embolic stroke in pregnancy or puerperium. Vessel imaging is essential for diagnosis. Histological thrombus analysis can provide insights into the pathophysiological mechanisms of stroke.

Exploring thrombus composition in cerebral venous thrombosis: the first case report with initial insights and implications for treatment advancements.

BACKGROUND: Endovascular thrombectomy (EVT) is a treatment option in patients with a cerebral venous thrombosis (CVT) who deteriorate despite anticoagulant treatment. Assessment of thrombus composition in CVT may provide insights into the pathophysiology of the disease and suggest new therapeutic strategies. CASE REPORT: A 47-year-old woman (smoking habit and estradiol/progesterone-releasing intra-uterine device) diagnosed with massive CVT underwent EVT (complete recanalization via aspiration catheter and stentriever) due to acute-onset left-sided weakness and dysarthria despite 72 h of full-dose subcutaneous low-molecular heparin. Two main reddish clots (maximum diameter 15 mm) were retrieved. Microscopic assessment showed an erythrocyte-rich thrombus (83.9% of entire thrombus surface) with layers of platelets/fibrin (lines of Zahn: 13.9% fibrin and 38.5% platelet [CD61+]). The immunological profile was dominated by neutrophils (30% MPO+), with neutrophil extracellular traps (NETs) in 1.9% of thrombus surface. T- (CD3+), B-lymphocytes (CD20+), and monocytes/macrophages (CD68+) were rather rare (2.2%, 0.7%, and 2.0% respectively). We found no evidence (0.0%) of hemosiderin and endothelial cells (CD34+). Full clinical recovery occurred prior to discharge. CONCLUSION: This is the first case report of a CVT with histologic assessment of the thrombus retrieved via EVT. Evaluating thrombi in CVT can provide key insights into disease pathophysiology and guide treatment advancements.

Ischemic Stroke and Vaccine-Induced Immune Thrombotic Thrombocytopenia following COVID-19 Vaccine: A Case Report with Systematic Review of the Literature.

INTRODUCTION: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus 2. It is characterized by thrombocytopenia, systemic activation of coagulation, extensive venous thrombosis, and anti-platelet factor 4 antibodies. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT, often associated with large vessel occlusion (LVO). Here, we describe a case of ischemic stroke with LVO after Ad26.COV2.S vaccine, then we systematically reviewed the published cases of ischemic stroke and VITT following COVID-19 vaccination. METHODS: We describe a 58-year-old woman who developed a thrombotic thrombocytopenia syndrome with extensive splanchnic vein thrombosis and ischemic stroke due to right middle cerebral artery (MCA) occlusion, 13 days after receiving Ad26.COV2.S vaccination. Then, we performed a systematic review of the literature until December 3, 2021 using PubMed and EMBASE databases. The following keywords were used: ("COVID-19 vaccine") AND ("stroke"), ("COVID-19 vaccine") AND ("thrombotic thrombocytopenia"). We have selected all cases of ischemic stroke in VITT. RESULTS: Our study included 24 patients. The majority of the patients were females (79.2%) and younger than 60 years of age (median age 45.5 years). Almost all patients (96%) received the first dose of an adenoviral vector-based vaccine. Ischemic stroke was the presenting symptom in 18 patients (75%). Splanchnic venous thrombosis was found in 10 patients, and cerebral venous thrombosis in 5 patients (21%). Most patients (87.5%) had an anterior circulation stroke, mainly involving MCA. Seventeen patients (71%) had an intracranial LVO. We found a high prevalence of large intraluminal thrombi (7 patients) and free-floating thrombus (3 patients) in extracranial vessels, such as the carotid artery, in the absence of underlying atherosclerotic disease. Acute reperfusion therapy was performed in 7 of the 17 patients with LVO (41%). One patient with a normal platelet count underwent intravenous thrombolysis with alteplase, while 6 patients underwent mechanical thrombectomy. A malignant infarct occurred in 9 patients and decompressive hemicraniectomy was performed in 7 patients. Five patients died (21%). CONCLUSION: Our study points out that, in addition to cerebral venous thrombosis, adenoviral vector-based vaccines also appear to have a cerebral arterial thrombotic risk, and clinicians should be aware that ischemic stroke with LVO, although rare, could represent a clinical presentation of VITT.

Chemotherapy-induced myasthenic crisis in thymoma treated with primary chemotherapy with curative intent on mechanical ventilation: a case report and review of the literature.

BACKGROUND: Thymoma is an uncommon cancer often associated with myasthenia gravis, an autoimmune disorder of the neuromuscular junction characterized by muscular fatigability. In patients with advanced nonmetastatic thymoma, primary chemotherapy may be required to induce tumor shrinkage and to achieve radical resection. Cancer chemotherapy has been anecdotally reported as a trigger factor for worsening of myasthenia gravis in thymic epithelial cancers. The study of uncommon cases of chemotherapy-related myasthenic crisis is warranted to gain knowledge of clinical situations requiring intensive care support in the case of life-threatening respiratory failure. CASE PRESENTATION: We report a case of an 18-year-old Caucasian woman with advanced Masaoka-Koga stage III type B2 thymoma and myasthenia gravis on treatment with pyridostigmine, steroids and intravenous immunoglobulins, who developed a myasthenic crisis 2 hours after initiation of cyclophosphamide/doxorubicin/cisplatin primary chemotherapy. Because of severe acute respiratory failure, emergency tracheal intubation, mechanical ventilation, and temporary (2 hours) discontinuation of chemotherapy were needed. Considering the curative intent of the multimodal therapeutic program, we elected to resume primary chemotherapy administration while the patient remained on mechanical ventilation. After 24 hours, the recovery of adequate respiratory function allowed successful weaning from respiratory support, and no further adverse events occurred. After 3 weeks, upon plasma exchange initiation with amelioration of myasthenic symptoms, a second course of chemotherapy was given, and in week 6, having documented partial tumor remission, the patient underwent radical surgery (R0) and then consolidation radiation therapy with 50.4 Gy in 28 fractions in weeks 15-20. CONCLUSIONS: This case report, together with the only four available in a review of the literature, highlights that chemotherapy may carry the risk of myasthenic crisis in patients affected by thymoma and myasthenia gravis. To our knowledge, this is the first reported case of chemotherapy continuation on mechanical ventilation in a patient with chemotherapy-induced myasthenic crisis requiring tracheal intubation. The lesson learned from the present case is that, in selected cases of advanced thymoma, the paradoxical worsening of myasthenia gravis during chemotherapy should not be considered an absolute contraindication for the continuation of primary chemotherapy with curative intent.

Prognostic nutritional index as a prognostic marker in glioblastoma: Data from a cohort of 282 Italian patients.

Preoperative prognostic nutritional index (PNI) is linked to the clinical outcome of patients with malignant tumours, however few studies have investigated its utility in predicting outcome in glioblastoma multiforme (GBM). We performed a retrospective study on adult patients with GBM in order to evaluate the impact of PNI on overall survival (OS), after adjusting for known prognostic factor (age, extent of surgery, Karnofsky performance status, radiochemotherapy). This is an Italian, multicentre, retrospective, cohort study. The patient's cohort includes 282 individuals with a newly diagnosed GBM followed in 3 Lombardia Hospitals In all cases the diagnosis was supported by histological data. Patient's information including sex, age at onset, Karnofsky performance status (KPS), extension of surgical resection (EOR), adjuvant treatment, antiepileptic treatment, serum variables and survival data were collected. Univariate and multivariate analysis did not reveal an association between PNI and overall survival in our series of GBM patients. PNI is a controversial marker for prognosis in GBM patients and further prospective studies are necessary to elucidate its role.

Antiepileptic treatment and survival in newly diagnosed glioblastoma patients: Retrospective multicentre study in 285 Italian patients.

Glioblastoma multiforme (GBM) has a dismal prognosis even with the best available treatment. Different studies have suggested a possible impact of antiepileptic drugs (AED) on survival in patients with GBM. A recent pooled analysis of prospective clinical trials in newly diagnosed GBM found no significant survival benefit in GBM patients treated with AED. We performed a retrospective study on adult patients with GBM in order to evaluate the impact of AED therapy on overall survival (OS), after adjusting for known prognostic factor (age, extent of surgery, Karnofsky performance status, radiochemotherapy). A total of 285 patients were analyzed. Of them 144 received a non-enzyme-inducing (NEIAED) and 95 an enzyme-inducing AED (EIAED). At univariate analysis the OS of patients receiving AED was not significantly different from that of patients not receiving an AED (HR 0.98, 95%CI 0.69-1.4, p = 0.925), moreover OS was not significantly different between patients receiving EIAED or NEIAED. At multivariate analysis a trend to more prolonged survival (HR 0.8, 95% CI 0.59-1.08, p = 0.15) was detected in patients treated with NEIAED. The question whether treatment with AED may increase OS in GBM patients remains unanswered and randomized extremely large controlled clinical trial would be necessary to elucidate the possible impact of AED on prognosis. In the meantime the use of AED in GBM patients, based on the presumed potential antitumour activity, is not recommended.

Pattern of care and outcome in elderly patients with glioblastoma: Data in 151 patients from 3 Lombardia Hospitals.

The appropriate treatment approach for elderly patients with glioblastoma multiforme (GBM) is unclear, although different studies suggest survival benefit in fit patients treated with radiotherapy and chemiotherapy after surgery. We performed a retrospective analysis of 151 patients older than 65years with GBM treated in 3 Lombardia Hospitals. In univariate regression analysis higher KPS (p=0.02), macroscopical total resection (p<0.003), radiotherapy (p<0.0001), chemotherapy (p<0.0001) and second line chemotheraphy (p=0.02) were of positive prognostic value. On the contrary older age (>70years), presence of seizure at onset and additional resection after tumor recurrence did not influence OS. Multivariate analysis revealed radiotherapy (HR 0.2 p<0.0001) and extent of surgery (HR 0.3, p=0,0063) as positive independent prognostic factors. Patients receiving radio-chemiotherapy displayed more treatment-related toxicities with a slightly prolonged OS versus those receiving hypofractionated radiotherapy. With the limits of a retrospective study, our data suggest that in elderly fit patients extensive surgery should be considered, moreover adjuvant treatments led to an increase in OS. Randomized controlled study are needed to develop treatment guidelines for elderly GBM patients and to assess whether the combination of post-surgical radio and chemiotherapy may be superior to hypofractionated radiotherapy and chemiotherapy in fit patients.

Endovascular Treatment of Ischemic Stroke: An Updated Meta-Analysis of Efficacy and Safety.

BACKGROUND: Recent randomized trials demonstrated the superiority of the mechanical thrombectomy over the best medical treatment in patients with acute ischemic stroke due to an occlusion of arteries of proximal anterior circulation. In this updated meta-analysis, we aimed to summarize the total clinical effects of the treatment, including the last trials. METHODS: We performed literature search of Randomized Crontrolled Trials (RCTs) published between 2010 and October 2016, comparing endovenous thrombolysis plus mechanical thrombectomy (intervention group) with best medical care alone (control group). We identified 8 trials. Primary outcomes were reduced disability at 90 days from the event and symptomatic intracranial hemorrhage. Statistical analysis was performed pooling data into the 2 groups, evaluating outcome heterogeneity. The Mantel-Haenszel method was used to calculate odds ratios (ORs). RESULTS: We analyzed data for 1845 patients (interventional group: 911; control group: 934). Mechanical thrombectomy contributed to a significant reduction in disability rate compared to the best medical treatment alone (OR: 2.087; 95% confidence interval [CI]: 1.718-2.535; P < .001). We calculated that for every 100 treated patients, 16 more participants have a good outcome as a result of mechanical treatment. No significant differences between groups were observed concerning the occurrence of symptomatic hemorrhage (OR: 1.021; 95% CI: 0.641-1.629; P = .739). CONCLUSION: Mechanical thrombectomy contributes to significantly increase the functional benefit of endovenous thrombolysis in patients with acute ischemic stroke caused by arterial occlusion of proximal anterior circulation, without reduction in safety. These findings are relevant for the optimization of the acute stroke management, including the implementation of networks between stroke centers.

Antioxidant and inflammatory biomarkers for the identification of prodromal Parkinson's disease.

OBJECTIVES: We explored the role of oxidative stress and inflammatory molecules as potential Parkinson (PD) biomarkers and correlated biological with non-motor abnormalities (olfactory impairment and dysautonomia), in patients with idiopathic REM behavior disorder (iRBD) (prodromal PD) and established PD. METHODS: We recruited 11 iRBD and 15 patients with idiopathic PD (Hohen&Yahr 1-3, on L-DOPA and dopamine agonists combination therapy) and 12 age- and sex-matched controls (CTRL). We measured total olfactory score (TOS), autonomic function [deep breathing (DB), lying to standing (LS) and Valsalva manoeuvre (VM) ratios], blood reduced glutathione (Br-GSH), oxidative stress and inflammatory markers (neopterin). RESULTS: Anosmia was similarly prevalent in iRBD (36%) and PD (33%) patients, but absent in CTRL. Orthostatic hypotension was more common among iRBD (73%) and PD (60%) than in CTRL (25%). By univariable ordinal logistic regression, TOS, Br-GSH, LS and VM ratio worsened from CTRL to iRBD and PD groups. Only reduced Br-GSH levels (p=0.037, OR=0.994; 95%CI 0.988-1.000) were independently associated to PD. TOS correlated with Br-GSH (R=0.34, p=0.037), VM ratio (R=0.43, p=0.015), and neopterin (rho=0.39, p=0.016). CONCLUSIONS: Reduced systemic antioxidant capacity is found in prodromal and overt PD and may represent, in association with olfactory loss and cardiovascular dysautonomia, a useful biomarker for an integrative, early diagnosis of PD.

Clinical Pregenetic Screening for Stroke Monogenic Diseases: Results From Lombardia GENS Registry.

BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease METHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. RESULTS: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.

NOTCH3 gene mutations in subjects clinically suspected of CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations involving loss or gain of a cysteine residue in the NOTCH3 gene. A cluster of mutations around exons 3 and 4 was originally reported. Identification of pathogenic mutation is important for diagnostic confirmation of the disease, however genetic counselling and testing of relatives at risk is critical in mutation carriers. METHODS: Mutation analysis of the NOTCH3 gene was performed through direct sequencing in 140 patients with clinical suspicion of CADASIL. Patients underwent genetic counselling pre and post testing. The 2-23 exons containing all EGF-like domains were screened. RESULTS: 14 familial forms of the disease have been identified with 14 different causative mutations in exons 2, 3, 4, 5, 7, 10, 14, 19, 20 and 22 of the NOTCH3 gene; no pathogenetic mutations have been identified in exons 6 and 8; several genetic variations both in coding as well as in intronic regions were identified too. CONCLUSIONS: Our data confirm the importance of screening the whole EGF-like domains region of NOTCH3 gene for the molecular diagnosis of CADASIL among the Italian population too. Moreover genetic variants different from loss or gain of a cysteine residue are identified and presented.

Thymoma-associated myasthenia gravis without acetylcholine receptor antibodies.

Patients with myasthenia gravis and thymoma usually present antibodies to the acetylcholine receptor (AchR-Ab). Only two cases of thymoma-associated myasthenia gravis without AchR-Ab have been previously reported. We describe a case of seronegative thymoma-associated myasthenia gravis as a further evidence of the variability of myasthenia gravis in terms of antibody profile and thymic pathological findings.

Alterations in the cerebral venous circulation as a cause of headache.

The alterations of the cerebral venous circulation are a rare but clinically important cause of headache. Although any process involving the cerebral veins or sinuses may cause headache, the most frequent and important are cerebral venous thrombosis and idiopathic intracranial hypertension. The headache of cerebral venous thrombosis does not have specific features and may be isolated; therefore, all patients with headache and risk factors for venous thrombosis should undergo the appropriate neuroradiologic examinations to rule out the diagnosis. In fact, early anticoagulant treatment may dramatically change the clinical outcome. Also idiopathic intracranial hypertension, if untreated, may have serious clinical consequences such as permanent visual loss. The pathogenesis of this disorder has not been clearly established and several possibilities involving the cerebral circulation are discussed.

An unusual transthyretin gene missense mutation (TTR Phe33Val) linked to familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy is a rare autosomal dominant disease, with clinical symptoms beginning in most kindreds within the third to seventh decades of life. The primary defect results from one of a number of mutations in the transthyretin (TTR) gene. Over 80 mutations in the TTR gene have been described. Most mutations give rise to adult onset progressive peripheral and autonomic neuropathy, due to amyloid deposition within the nerves, and often subclinical cardiac amyloid and vitreous deposits. We report here the clinical and molecular characterization of a rare TTR missense mutation discovered in a young woman from Macedonia, showing severe axonal sensory-motor polyneuropathy, restrictive cardiomyopathy and bilateral vitreous deposits. The transthyretin gene, analyzed by direct nucleotide sequencing, demonstrated a T to G transversion at nucleotide 183 in the exon 2 which is predicted to cause a heterozygous valine for phenylalanine substitution at codon 33 (TTR Phe33Val). This mutation has been previously reported only twice, without complete clinical descriptions.