IL-1 Beta-A Biomarker for Ischemic Stroke Prognosis and Atherosclerotic Lesions of the Internal Carotid Artery.

Background and Objectives: Stroke is a leading cause of mortality and morbidity worldwide. Treatment of this pathology is still under development and its risk factors remain to be determined. Therefore, we aim to determine the role of interleukin-1 beta in atherosclerotic lesions of the internal carotid artery as a risk factor for stroke and the role of this biomarker in stroke prognosis. Materials and Methods: This study enrolled 56 patients diagnosed with ischemic stroke in the anterior vascular territory (AVT) and posterior vascular territory (PVT). All the patients had venous blood collected at admission and 7 days after the onset of the cerebral ischemia in order to determine the plasma concentration of interleukin-1 beta. At the same time, an extracranial carotid ultrasound was performed. Results: The interleukin-1 beta collected at admission was positively correlated with the NIHSS at admission (Pearson index 0.424), and both measurements were correlated with carotid stenosis (Spearmen correlation index of 0.529 and 0.653, respectively). Conclusions: Interleukin-1 beta could be a reliable biomarker for stroke prognosis and the development of atherosclerotic lesions of the internal carotid.

Has-miR-129-5p's Involvement in Different Disorders, from Digestive Cancer to Neurodegenerative Diseases.

At present, it is necessary to identify specific biochemical, molecular, and genetic markers that can reliably aid in screening digestive cancer and correlate with the degree of disease development. Has-miR-129-5p is a small, non-coding molecule of RNA, circulating in plasma, gastric juice, and other biological fluids; it plays a protective role in tumoral growth, metastasis, etc. Furthermore, it is involved in various diseases, from the development of digestive cancer in cases of downregulation to neurodegenerative diseases and depression. Methods: We examined meta-analyses, research, and studies related to miR-129-5-p involved in digestive cancer and its implications in cancer processes, as well as metastasis, and described its implications in neurological diseases. Conclusions: Our review outlines that miR-129-5p is a significant controller of different pathways, genes, and proteins and influences different diseases. Some important pathways include the WNT and PI3K/AKT/mTOR pathways; their dysregulation results in digestive neoplasia and neurodegenerative diseases.

A Severity Score and Outcome Prediction in Patients that Suffered an Ischemic Stroke.

Background: Stroke is the main cause of disability and exitus worldwide. The prediction of mortality of this pathology represents a major challenge. More than that, the infection with the SARS-CoV-2 virus is a challenge for every clinician worldwide, and hypercoagulability is one of its biggest concerns that can lead to stroke. Objective: Our aim was to develop a severity stroke index for both SARS-CoV-2 stroke patients and noninfected stroke patients which we hope to be helpful in patient's management. Methods: We conducted a prospective study during January 2021-June 2021 which included 80 patients who suffered an ischemic stroke, 40 of which had both stroke and SARS-CoV-2 infection. We have established a panel of biomarkers including CRP, IL-6, fibrinogen, ESR, D-dimer, leucocytes, lymphocytes, and NLR and compared the results of our two cohorts. Results: SARS-CoV-2 stroke patients have experienced elevated levels of biomarkers that rise in inflammation such as hs-CRP, IL-6, and D-dimer, comparing to noninfected stroke patients. Also, the probability of exitus in SARS-CoV-2 patients is 4.2 times higher than in noninfected subjects. With regard to stroke severity, we have concluded that a NIHSS score higher than 15 points considerably influences the death rate, the probability of exitus being 9.16 times higher than in NIHSS score lower than 15. Conclusion: Based on our result, we have established a severity score index which includes NIHSS score, age, gender, the presence/absence of COVID-19 infection, and the following biomarkers: hs-PCR, IL-6, D-dimer, fibrinogen, and ESR, which can be used as a tool to guide patient's management.

Non-Aneurysmal Perimesencephalic Subarachnoid Hemorrhage: A Literature Review.

Spontaneous non-aneurysmal subarachnoid haemorrhage (NAPMSAH) (addressing point 1) is a relatively rare occurrence in clinical settings as it is rarely misdiagnosed and usually involves a significantly better prognosis than the classical aneurysmal pattern. We hereby focused on a comprehensive analysis of this distinct pathological entity with the purpose of analysing possible pathophysiological entities, outcomes and treatment options involving this diagnosis with a focus on demographical, epidemiological and clinical data. The clinical setting includes focal neurological signs related to the anatomical structures, while computer tomography followed by tomographic angiography are the most common diagnosis tools, with a typical hyperdense lesion involving the midbrain, fourth ventricle and subthalamic areas without an angiographic correspondent, such as an aneurysmal pathology. Further investigations can also be used to highlight this diagnosis, such as interventional angiography or magnetic resonance imaging. Given the rarity of this condition and its relatively better prognosis, treatment options usually remain conservative. In the present review, the main characteristics of NAPMSAH are discussed.

Prognostic markers for ischemic stroke - are they truly reliable?

Background: Stroke is one of the leading causes of mortality and morbidity worldwide. Despite extensive research, to this date there is no panel of biomarkers for the prevention and prognosis of ischemic stroke and there is still much incomplete and insufficiently researched information. Aim: We conducted a prospective, observational study between January and June 2020. The main objective of this study was to clarify the role of inflammation markers, i.e. neutrophil/ lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), high-sensitivity C - reactive protein (hsCRP) in ischemic stroke and whether there is or not a correlation between these markers and carotid stenosis. Study design: In the study we included 150 subjects divided in two groups: study group - 100 subjects and control group - 50 subjects. Methods: Data collected during the research (at the time of patient admission): 1) biological sample: 5 ml of peripheral blood were collected in a vial with clot activator and separating gel, from which the following laboratory tests were performed: hsCRP, neutrophils, lymphocytes, platelets. NLR and PLR were subsequently calculated as the ratio of neutrophils to lymphocytes, respectively platelets and lymphocytes), 2) paraclinical examinations: extracranial carotid Doppler ultrasound examination. Results: The results were impressive: high-sensitivity C reactive protein (hsCRP), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were strongly, respectively moderately correlated with the severity of stroke (the severity being established with the NIHS (National Institute of Health Stroke) score. None of the inflammation markers included in the present study was correlated with carotid stenosis. Conclusion: hsCRP, NLR and PLR may potentially be prognostic markers for ischemic stroke, being of major help in preventing its possible complications.

Pharmacological Management of Myasthenia Gravis: A Century of Expert Opinions in Cecil Textbook of Medicine.

BACKGROUND: Advances in drug therapy for myasthenia gravis have had a significant impact on the quality of life and work potential of a substantial majority of affected persons and has contributed to a remarkable decrease in the frequency and severity of complications, hospitalizations, and mortality. STUDY QUESTION: What are the milestones of the changes in the expert approach to the pharmacological management of myasthenia in the past century? STUDY DESIGN: To determine the changes in the experts' approach to the management of myasthenia gravis, as presented in a widely used textbook in the United States. DATA SOURCES: The chapters presenting the management of myasthenia gravis in the 26 editions of Cecil Textbook of Medicine published from 1927 to 2020. RESULTS: Adequate feeding, absolute rest in bed, and "tonics" were the only interventions recommended for the care of patients with myasthenia gravis in 1927. Ephedrine and glycine were used in the early 1930s. Treatment with the anticholinesterases physostigmine and neostigmine was recommended in 1937, 3 years after Mary Walker discovered it in the United Kingdom. Immunosuppressant pharmacological interventions with prednisone and azathioprine have been considered the standard since 1975, and intravenous immune globulin was added to usual care in 1996. The newer immunosuppressant drugs mycophenolate, cyclosporine, and tacrolimus have expanded the arsenal since 2008, and the monoclonal antibodies rituximab and eculizumab have been mentioned in the textbooks published in 2012-2020. The first randomized clinical trial of drug therapy for myasthenia gravis was published in 1987. CONCLUSIONS: The pharmacological management of myasthenia gravis was revolutionized by the epiphany of an astute clinician in the 1930s. Immunosuppressant treatment was a logical step once the autoimmune nature of the condition was established. The major therapeutic advances highlight the values of empiricism and persistent attention to detail in treating relatively rare chronic disorders.

The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis.

Th17 cells, known as a highly pro-inflammatory subtype of Th cells, are involved very early in numerous aspects of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) neuropathology. A crucial event for the formation and accumulation of MS lesions is represented by the disruption of the blood brain barrier (BBB) in relapsing-remitting MS. Th17 cells also contribute to the progression of MS/EAE. These events will allow for the passage of inflammatory cells into the brain. Secondary to this, increased recruitment of neutrophils occurs, followed by increased protease activity that will continue to attract macrophages and monocytes, leading to brain inflammation with sustained myelin and axon damage. This review focuses mainly on the role of Th17 cells in penetrating the BBB and on their important effects on BBB disruption via their main secretion products, IL-17 and IL-22. We present the morphological aspects of Th17 cells that allow for intercellular contacts with BBB endothelial cells and the functional/secretory particularities of Th17 cells that allow for intercellular communications that enhance Th17 entry into the CNS. The cytokines and chemokines involved in these processes are described. In conclusion, Th17 cells can efficiently cross the BBB using pathways distinct from those used by Th1 cells, leading to BBB disruption, the activation of other inflammatory cells and neurodegeneration in MS patients.

THERAPEUTIC PLASMA EXCHANGE AND DOUBLE FILTRATION PLASMAPHERESIS IN SEVERE NEUROIMMUNE DISORDERS.

Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique, which removes large molecular weight particles such as autoantibodies from plasma. TPE is accepted by the American Society for Apheresis as first line treatment for some severe neuroimmune disorders. Double filtration plasmapheresis (DFPP) is a newer technique in which plasma is not entirely removed, only the antibodies, using special filters. High-dose intravenous immunoglobulins are an alternative treatment for these patients but are much more expensive. We reviewed medical records of 20 patients with severe neurological diseases requiring TPE or DFPP. We analyzed the indications, complications and efficacy of these procedures. After completing the procedures, neurological improvement was recorded in 80% of the patients, 5% had no improvement, and the mortality was 15%. The rate of neurological improvement was similar to other studies. None of the patients presented catheter related complications. Systemic complications were mild, transient and completely reversible.

Trigeminal Meningioma in a Patient with Tardive Dyskinesia as Only Symptom.

Most meningiomas are benign, encapsulated tumors (95% of the cases), generally undergoing a limited number of genetic aberrations. We present the case of a 74-year-old patient with no significant pathological history, who is admitted to the neurology ward for orofacial dyskinesias accompanied by hypoesthesia in the left hemiface, a symptomatology that had started insidiously about two months before and worsened progressively over the past 3 weeks. A cerebral MRI was performed which revealed a small mass with discrete T2 hyperintensity and T1 iso-signal compared to the gray matter located in the left pontine cistern, with a large, well-defined base at the level of the cerebral tentorium. The diagnosis of trigeminal meningioma was established and the treatment was started, after hearing the opinion of a neurosurgeon.

Painful tonic spasms and brainstem involvement in a patient with neuromyelitis optica spectrum disorder.

Neuromyelitis optica (NMO) is an inflammatory-demyelinating disease of the central nervous system classically characterized by optic neuritis and severe myelitis. New diagnostic criteria defined neuromyelitis optica spectrum disorder as limited forms of NMO or diverse neurologic presentations in the presence of specific antiaquaporin-4 antibodies. We report the case of a 57-year-old woman admitted in our department for recurrent attacks of optic neuritis, tetraparesis with severe painful tonic spasms of the left limbs and brainstem involvement. Painful tonic spasms have been described as movement disorders associated with multiple sclerosis, but a growing number of reports describe them in cases of NMO.