Multiple Ischemic Strokes Research Articles

Immune cell profiling in the cerebrospinal fluid of patients with primary angiitis of the central nervous system reflects the heterogeneity of the disease

Primary angiitis of the central nervous system (PACNS) is a rare and heterogeneous inflammatory disease of the CNS vasculature with poorly understood pathophysiology. Comprehensive immune-cell phenotyping revealed increased frequencies of leukocytes in the cerebrospinal fluid (CSF) of PACNS patients compared to patients with multiple sclerosis, ischemic stroke, and somatoform disorders (n = 18 per group). Changes in the intrathecal immune-cell profile were heterogeneous in PACNS. While proportions of T-cell subsets remained unaltered, some PACNS patients showed a shift toward NK- or B cells. Intrathecal immunoglobulin synthesis was observed in a subgroup of PACNS patients with an increased frequency of antibody producing plasma cells.

Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic Target for Ischemic Stroke.

BackgroundIschemic stroke is a complex disease with multiple etiologies and clinical manifestations. Paired immunoglobulin‐like receptor B (PirB), which is originally thought to function exclusively in the immune system, is now also known to be expressed by neurons. A growing number of studies indicate that PirB can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the study is to investigate whether PirB can be an attractive theranostic target for ischemic stroke.Methods and ResultsFirst, we investigated the spatial‐temporal expression of PirB in multiple ischemic stroke models, including transient middle cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the neuronal oxygen glucose deprivation model. Then, anti‐PirB immunoliposome nanoprobe was developed by thin‐film hydration method and investigated its specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB) protein delivered by polyethylene glycol–modified nanoliposome was used as a therapeutic reagent for ischemic stroke by blocking PirB binding to its endogenous ligands. These results showed that PirB was significantly upregulated after cerebral ischemic injury in ischemic stroke models. Anti‐PirB immunoliposome nanoprobe was successfully developed and specifically bound to PirB in vitro. There was accumulation of anti‐PirB immunoliposome nanoprobe in the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved ischemic stroke model recovery by liposomal delivery system.ConclusionsThese data indicated that PirB was a significant element in the pathological process of cerebral ischemia. Therefore, PirB may act as a novel theranostic target for ischemic stroke.

C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective.

Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses. C-PC promoted white matter regeneration in rats and mice affected by experimental autoimmune encephalomyelitis. Electron microscopy analysis in cerebral cortex from ischemic rats revealed a potent remyelinating action of PCB treatment after stroke. Among others biological processes, we discussed the role of regulatory T cell induction, the control of oxidative stress and pro-inflammatory mediators, gene expression modulation and COX-2 inhibition as potential mechanisms involved in the C-PC and PCB effects on the recruitment, differentiation and maturation of oligodendrocyte precursor cells in demyelinated lesions. The assembled evidence supports the implementation of clinical trials to demonstrate the recovery effects of C-PC and PCB in these diseases.

ESTABLISHING THE CORRECT MANAGEMENT IN A PATIENT WITH MULTIPLE CRYPTOGENIC STROKES: ANTIPLATELET VS ANTICOAGULANT THERAPY

Cryptogenic strokes represent a category of ischemic strokes in which there is no well-defined cause identified. For that matter, choosing between antiplatelet and anticoagulant therapy can be challenging. We present the case of a 44 year old Caucasian male with a history of multiple ischemic strokes, with thrombophilia, but no atrial fi brillation or known cardio-embolic sources, who initially received anticoagulant treatment, which was switched in 2015 with Clopidogrel. Aspirin was added in 2017 after having a TIA in the left MCA territory. Despite dual antiplatelet therapy, the patient developed ischemic stroke in the left MCA territory, for which re-initiation of anticoagulant treatment was decided. Holter ECG, transthoracic and transesophageal echocardiography were performed, but failed to identify a cause.

Excess Interleukin-6 Production and Multiple Ischemic Strokes – What is the Link?

Excess Interleukin-6 Production and Multiple Ischemic Strokes – What is the Link?

Multiple recurrent ischaemic strokes in a patient with cancer: is there a role for the initiation of anticoagulation therapy for secondary stroke prevention?

A 52-year-old woman with a medical history of cervical and thyroid cancer, hypertension, dyslipidaemia, uncontrolled diabetes and heavy smoking was diagnosed with a new metastatic cholangiocarcinoma. While undergoing palliative chemotherapy,...

Spontaneous bilateral internal carotid artery dissection: a case report and literature review

A patient with multiple ischemic stroke due to spontaneous bilateral internal carotid artery dissection (ICAD) was reported and the epidemiology, neuroimaging, clinical characteristics and treatment of spontaneous bilateral ICAD were reviewed. Spontaneous bilateral ICAD mostly occurs in young and middle-aged individuals and the clinical manifestations are mainly stroke(71.1%), headache and neck pain(62.2%), Horner′s syndrome(15.6%) and cranial nerve palsy(11.1%). Cervical axial T1-weighted fat-suppressed image is an alternative to DSA to make the definite diagnosis. Antithrombotic therapy is regularly used and the general clinical outcome is good. Cervical arterial dissection is one of the most common causes of stroke in young and middle-aged patients. Cervical MRI T1-weighted fat suppressed image is crucial for timely diagnosis and initiation of appropriate clinical intervention. Key words: Carotid artery internal; Stroke; Cervical MRI

Multiple Acute Ischemic Strokes due to Cerebral AVM Vascular Steal Phenomenon (P2.298)

Multiple Acute Ischemic Strokes due to Cerebral AVM Vascular Steal Phenomenon (P2.298)

DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury.

Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke. The aim of the current study was to determine if DRα1-MOG-35-55 treatment of a fluid percussion injury (FPI) mouse model of TBI could reduce the lesion size and improve disease outcome measures. Neurodeficits, lesion size, and immune responses were determined to evaluate the therapeutic potential and mechanisms of neuroprotection induced by DRα1-MOG-35-55 treatment. The results demonstrated that daily injections of DRα1-MOG-35-55 given after FPI significantly reduced numbers of infiltrating CD74+ and CD86+ macrophages and increased numbers of CD206+ microglia in the brain concomitant with smaller lesion sizes and improvement in neurodeficits. Conversely, DRα1-MOG-35-55 treatment of TBI increased numbers of circulating CD11b+ monocytes and their expression of CD74 but had no detectable effect on cell numbers or marker expression in the spleen. These results demonstrate that DRα1-MOG-35-55 therapy can reduce CNS inflammation and significantly improve histological and clinical outcomes after TBI. Future studies will further examine the potential of DRα1-MOG-35-55 for treatment of TBI.

Fulminant Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is increasingly being recognized as a diagnosis in patients presenting with thunderclap headaches. In the vast majority of the cases, the syndrome follows a benign course and patients recover completely without any significant therapeutic intervention. In the rarest of cases, RCVS follows a monophasic course with rapid worsening, severe neurological deficits, and poor outcomes. We present the case of a 25-year-old female who presented with headaches which were worsening over 1 week. She was admitted to the hospital and rapidly worsened to develop severe neurological deficits over the next day. Initial computed tomography scan showed areas of hemorrhage and multiple ischemic strokes. Computed tomography angiogram and a conventional cerebral angiogram both revealed multifocal vasoconstriction, highly suggestive of RCVS. Despite aggressive medical and surgical management, the patient continued to worsen and eventually died. Autopsy findings did not show evidence of vasculopathy or any other underlying disorder, further supporting the diagnosis of RCVS. The RCVS is usually a benign self-remitting condition which commonly affects young females and presents with an insidious onset of headaches. Rarely, it can have a fulminant course with devastating outcomes. This case illustrates an exceptionally uncommon clinical course of RCVS and the challenges in its treatment.

Cytoprotection in Multiple Sclerosis and Ischemic Stroke with C-Phycocyanin and Phycocyanobilin

Cytoprotection in human diseases can be achieved by avoiding and ameliorating tissue damage or by restoring the homeostatic balance either as a local or a systemic defense response. Multiple Sclerosis (MS) and Ischemic Stroke (IS) although being different central nervous system diseases, have common pathogenic aspects such as a deregulated inflammatory response, a toxic redox imbalance and a prominent neuronal dysfunction.

Association of multiple ischemic strokes with mortality in incident hemodialysis patients: an application of multistate model to determine transition probabilities in a retrospective observational cohort.

BackgroundLittle is known about the effect of multiple, or subsequent, ischemic strokes in patients receiving hemodialysis.MethodsWe undertook a retrospective cohort study of incident hemodialysis patients with Medicare coverage who had experienced a first ischemic stroke. Factors associated with either a subsequent ischemic stroke or death following a first new stroke were modeled. A multistate model with Cox proportional hazards was used to predict transition probabilities from first ischemic stroke to either subsequent stroke or to death, and the demographic and clinical factors associated with the respective transition probabilities were determined. Effect of a subsequent ischemic stroke on survival was quantified.ResultsOverall, 12,054 individuals (mean age 69.7 years, 41.3 % male, 53.0 % Caucasian and 34.0 % African-American) experienced a first new ischemic stroke. Female sex was associated with an increased risk of having a subsequent ischemic stroke (adjusted hazard ratio 1.37, 95 % confidence intervals 1.20 – 1.56, P < 0.0001); African-Americans, as compared to Caucasians, had lower likelihood of dying after a first new ischemic stroke (0.81, 0.77 – 0.85, P < 0.0001). A subsequent stroke trended towards having a higher likelihood of transitioning to death compared to a first new ischemic stroke on dialysis (1.72, 0.96 – 3.09, P = 0.071). When a subsequent ischemic stroke occurs at 24 months, probability of survival dropped >15 %, in absolute terms, from 0.254 to 0.096, with substantial drops observed at subsequent time points such that the probability of survival was more than halved.ConclusionsLikelihood of subsequent ischemic stroke and of survival in hemodialysis patients appears to vary by sex and race: females are more likely than males to experience a subsequent ischemic stroke, and Caucasians are more likely than African-Americans to die after a first new ischemic stroke. The risk of a transitioning to a subsequent stroke (after having had a first) increases until about 1 year, then decreases. Subsequent strokes are associated with decreased probability of survival, an effect which increases as time since first stroke elapses. This information may be of assistance to clinicians when counseling hemodialysis patients about the implications of recurrent ischemic stroke.

Thrombosis at the Site of Pulmonary Venous Anastomosis Following Lung Transplantation Presenting with Multiple, Bilateral, Supra- and Infra-Tentorial Ischemic Strokes in the Setting of a Known Patent Foramen Ovale (P4.355)

Thrombosis at the Site of Pulmonary Venous Anastomosis Following Lung Transplantation Presenting with Multiple, Bilateral, Supra- and Infra-Tentorial Ischemic Strokes in the Setting of a Known Patent Foramen Ovale (P4.355)

A Case of Multiple Recurrent Ischemic Stroke in a Patient with Cholangiocarcinoma and Initiation of Anticoagulation Therapy for Secondary Stroke Prevention (P4.342)

A Case of Multiple Recurrent Ischemic Stroke in a Patient with Cholangiocarcinoma and Initiation of Anticoagulation Therapy for Secondary Stroke Prevention (P4.342)

Cerebral Gas Embolism - A Serious Complication of CO&lt;SUB&gt;2&lt;/SUB&gt; Angiography

Carbon dioxide angiography is routinely used for vascular imaging and endovascular procedures. It is very useful in patients with allergy to iodinated contrast agents or with poor renal function. It is relatively safe to use. We describe first case of cerebral gas embolism leading to multiple bilateral ischemic strokes in a patient receiving carbon dioxide angiography for workup of thrombosed arm arteriovenous fistula.

Risk of Stroke in Patients with Multiple Myeloma: A Nationwide Population-Based Study

Background. Patients with multiple myeloma are at risk of thromboembolism. However, studies investigating the relationship between multiple myeloma and ischemic stroke are limited. Therefore, we conducted a nationwide population-based study to investigate the risk of stroke among patients with multiple myeloma and the association between myeloma-related therapy and development of stroke.Material and methods. We recruited patients with newly diagnosed multiple myeloma aged 20 years or older without antecedent cerebrovascular events from Taiwan’s National Health Insurance database between January 1, 2004 and December 31, 2011. Hazard ratios (HRs) of stroke risk for patients with multiple myeloma compared with an age-, sex-, and comorbidity-matched cohort were calculated by Cox proportional regression analysis. Additionally, therapeutic agents were put into Cox models as time-dependent covariates to avoid immortal time bias.Results. This study consisted of 2,296 patients with multiple myeloma and 22,960 matched individuals, with a median age of 65 years (interquartile range 55-73). One hundred thirteen cerebrovascular events developed among 2,296 patients with multiple myeloma, with a follow-up of 4,119.2 person-years. The stroke incidence was 1.23 times higher in the multiple myeloma cohort than in the matched cohort (27.4 vs. 22.2 per 1,000 person-years), with an age-, sex-, and comorbidity-adjusted HR of 1.38 (95% confidence interval [CI] 1.14-1.67; P < 0.001). The multivariable Cox proportional hazard models showed bortezomib treatment as an independent risk factor determining the subsequent stroke in patients with multiple myeloma (adjusted HR 2.01; 95% CI 1.22-3.28; P = 0.006). This effect was not seen with steroids, thalidomide, or other chemotherapy agents.Conclusion. Our study reveals an increased risk of stroke among patients with multiple myeloma compared with the matched cohort. Bortezomib treatment is associated with a higher risk of stroke in patients with multiple myeloma. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a potentially devastating clinical problem. Despite advances in the diagnosis and treatment of SAH, outcome remains unfavorable. An increased inflammatory state, one that is characterized by enhanced leukocyte trafficking has been reported to contribute to neuronal injury in association with multiple brain insults, including hemorrhagic and ischemic stroke. This study was designed to investigate, in rats, the neuropathologic consequences of heightened leukocyte trafficking following SAH, induced via endovascular perforation of the anterior cerebral artery. Experiments focused on the initial 48h post-SAH and sought to establish whether blockade of vascular adhesion protein-1 (VAP-1), with LJP-1586, was able to provide dose-dependent neuroprotection. Treatment with LJP-1586 was initiated at 6h post-SAH. An intravital microscopy and closed cranial window system, that permitted examination of temporal patterns of rhodamine-6G-labeled leukocyte adhesion/extravasation, was used. Effects of LJP-1586 on neurologic outcomes and leukocyte trafficking at 24h and 48h post-SAH were examined. In VAP-1-inhibited vs control rats, results revealed a significant attenuation in leukocyte trafficking at both 24h and 48h after SAH, along with an improvement in neurologic outcome. In conclusion, our findings support the involvement of an amplified inflammatory state, characterized by enhanced leukocyte trafficking, during the first 48h after SAH. VAP-1 blockade yielded neuroprotection that was associated with an attenuation of leukocyte trafficking and improved neurologic outcome.

Role of CCR2 in inflammatory conditions of the central nervous system.

CC chemokine receptor 2 (CCR2) plays important roles in extravasation and transmigration of monocytes under inflammatory conditions. CCR2 and its ligands have been extensively studied in a range of inflammatory diseases in the central nervous system (CNS), including multiple sclerosis, Alzheimer's disease and ischemic stroke. This brief review summarizes our current understanding of the physiologic and pathologic roles of CCR2, focusing on its involvement in CNS inflammatory diseases. There appears to be a rationale for exploring therapies involving CCR2 inhibition in multiple sclerosis and ischemic stroke, but there is also evidence for immunomodulatory and protective effects of CCR2 activity during CNS inflammation. The critical balance between protective and detrimental roles of CCR2-dependent recruitment of leukocytes must therefore be carefully examined to guide safe and effective development of any therapies involving CCR2 modulation.

Sensory cortex lesion triggers compensatory neuronal plasticity

BackgroundLesions to the human brain often cause dramatic impairments in the life of patients because of the very limited capacity of the mammalian nervous system to regenerate. On the other hand, neuronal tissue has a high capacity to reorganize itself so that loss of function due to brain damage may be compensated through neuroplastic reorganization of undamaged tissue in brain regions adjacent or contralateral to the lesion site. In this study we investigated the effect of serial lesions of the auditory cortices (AC) in both hemispheres of Mongolian gerbils on discrimination performance for fast amplitude modulated tones (AM). Healthy animals were trained to discriminate two fast AM, an ability that has previously been shown to critically depend on cortical processing. Their ability to maintain significant discrimination performance was retested after unilateral AC lesion, and again after lesion of the contralateral AC, with 15 days of continuing training in between the two lesions.ResultsAfter bilateral cortical ablation of both AC and 45 days of training the animals show no change in pure tone detection threshold as measured with modulation of the acoustic startle reflex which has been shown to rely on subcortical structures. In contrast to simultaneous bilateral ablation of AC that results in complete loss of AM discrimination ability in this paradigm we found compensatory plasticity that seems to be triggered by unilateral cortical ablation with subsequent training and that is able to almost fully compensate for the lost cortical functions.ConclusionsOur results demonstrate that AM discrimination ability that normally depends on AC may be transferred to other brain regions when the brain has time to activate compensatory plasticity between the lesions of the two AC hemispheres. For this process to take place obviously one intact AC hemisphere is needed. This finding may open perspectives for new therapeutic strategies that may alleviate the impairments after multiple ischemic strokes.

Stroke after Initiating IV Penicillin for Neurosyphilis: A Possible Jarisch-Herxheimer Reaction.

Introduction. Syphilis incidence has increased in the US in the last decade. Jarisch-Herxheimer reaction (JHR) is a well-documented adverse effect of penicillin treatment in syphilis. Stroke has not been reported as part of its phenomenology. Case Report. A 57-year-old man presented with worsening memory. His minimental status examination score was 14/30. Serum RPR test was positive and VDRL test in the CSF was reactive. Within six hours of first dose of IV crystalline penicillin G, he was found to have hemineglect and difficulty moving the left leg. MRI of the brain showed multiple acute ischemic strokes. Immediate MRA ruled out vascular occlusion. Penicillin treatment was stopped. Four hours later, he was found to be febrile and had two episodes of generalized tonic-clonic seizures. Conclusions. We report a case of confirmed neurosyphilis with no known modifiable stroke risk factors, who developed acute ischemic stroke and other constitutional symptoms consistent with JHR after IV penicillin. This is the first reported case in literature where an acute ischemic stroke can be attributed to Jarisch-Herxheimer reaction. Given an increase in incidence of syphilis in recent years, our case underlies the importance of keeping in mind potential catastrophic drug adverse reactions in neurosyphilis patients.