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1.
BMC Neurol ; 21(1): 37, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504323

RESUMO

BACKGROUND: Manifestations of intractable hyponatremia and hypokalemia in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy have been rarely reported. CASE PRESENTATION: A 75-year-old male patient presented as the case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and intractable hypokalemia, showed fever, fatigue, and mental disorders. Signs and symptoms of meningoencephalitis, ataxia, and cognitive abnormalities. Magnetic resonance imaging (MRI) revealed multiple white matter lesions of the central nervous system. He had GFAP-IgG in the cerebrospinal fluid (CSF). After treatment with corticosteroids, his symptoms were alleviated gradually, and the level of electrolytes was normal. However, head contrast-enhanced MRI + susceptibility-weighted imaging (SWI) showed a wide afflicted region, and the serum GFAP-IgG turned positive. Considering the relapse of the disease, ha was treated with immunoglobulin and mycophenolate mofetil (MMF) to stabilize his condition. CONCLUSION: This case showed a rare disease with uncommon manifestations, suggesting that careful examination and timely diagnosis are essential for disease management and satisfactory prognosis.


Assuntos
Corticosteroides/uso terapêutico , Astrócitos/patologia , Proteína Glial Fibrilar Ácida/imunologia , Doenças do Sistema Nervoso/tratamento farmacológico , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/líquido cefalorraquidiano , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imagem por Ressonância Magnética , Masculino , Meningoencefalite/imunologia , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/patologia , Doenças Raras
2.
Life Sci ; 271: 119111, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33513398

RESUMO

BACKGROUND: Sevoflurane (Sevo) is neuroprotective in brain damage, thus our objective was to further investigate the impact of Sevo treatment on nerve regeneration and repair of neurological deficit in brain damage rats by regulating miR-490-5p and cyclin-dependent kinases 1 (CDK1). METHODS: The rat middle cerebral artery occlusion model was established. miR-490-5p and CDK1 levels in brain tissues were tested. The behavioral changes, the number of glial fibrillary acidic protein (GFAP) positive cells, ionized calcium-binding adapter molecule-1 (Iba-1) and Nestin mRNA expression, the survival and apoptosis of neurons in peripheral tissues of infarct areas were detected by a series of assays. Furthermore, the target relationship between miR-490-5p and CDK1 was verified. RESULTS: miR-490-5p was reduced and CDK1 was raised in brain tissues of brain damage rats. Sevo raised miR-490-5p and decreased CDK1 to improve neurological deficits, reduce apoptotic neurons, suppress expression levels of GFAP and Iba-1, and increase Nestin expression and the number of surviving neurons in peripheral tissue in infarct area, and alleviate the pathological changes of brain tissues of brain damage rats. CDK1 was negatively regulated by miR-490-5p. CONCLUSION: Our study presents that Sevo treatment is involved in neurogenesis and repair of neurological deficit of brain damage rats via up-regulating miR-490-5p and inhibiting CDK1.


Assuntos
Proteína Quinase CDC2/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , MicroRNAs/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Doenças do Sistema Nervoso/metabolismo , Sevoflurano/uso terapêutico , Animais , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , MicroRNAs/antagonistas & inibidores , Regeneração Nervosa/fisiologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sevoflurano/farmacologia
3.
Mol Neurobiol ; 58(1): 106-117, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32897518

RESUMO

The SARS-CoV-2 virus that is the cause of coronavirus disease 2019 (COVID-19) affects not only peripheral organs such as the lungs and blood vessels, but also the central nervous system (CNS)-as seen by effects on smell, taste, seizures, stroke, neuropathological findings and possibly, loss of control of respiration resulting in silent hypoxemia. COVID-19 induces an inflammatory response and, in severe cases, a cytokine storm that can damage the CNS. Antimalarials have unique properties that distinguish them from other anti-inflammatory drugs. (A) They are very lipophilic, which enhances their ability to cross the blood-brain barrier (BBB). Hence, they have the potential to act not only in the periphery but also in the CNS, and could be a useful addition to our limited armamentarium against the SARS-CoV-2 virus. (B) They are non-selective inhibitors of phospholipase A2 isoforms, including cytosolic phospholipase A2 (cPLA2). The latter is not only activated by cytokines but itself generates arachidonic acid, which is metabolized by cyclooxygenase (COX) to pro-inflammatory eicosanoids. Free radicals are produced in this process, which can lead to oxidative damage to the CNS. There are at least 4 ways that antimalarials could be useful in combating COVID-19. (1) They inhibit PLA2. (2) They are basic molecules capable of affecting the pH of lysosomes and inhibiting the activity of lysosomal enzymes. (3) They may affect the expression and Fe2+/H+ symporter activity of iron transporters such as divalent metal transporter 1 (DMT1), hence reducing iron accumulation in tissues and iron-catalysed free radical formation. (4) They could affect viral replication. The latter may be related to their effect on inhibition of PLA2 isoforms. Inhibition of cPLA2 impairs an early step of coronavirus replication in cell culture. In addition, a secretory PLA2 (sPLA2) isoform, PLA2G2D, has been shown to be essential for the lethality of SARS-CoV in mice. It is important to take note of what ongoing clinical trials on chloroquine and hydroxychloroquine can eventually tell us about the use of antimalarials and other anti-inflammatory agents, not only for the treatment of COVID-19, but also for neurovascular disorders such as stroke and vascular dementia.


Assuntos
Antimaláricos/uso terapêutico , /tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Animais , Antimaláricos/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Humanos , Doenças do Sistema Nervoso/metabolismo , Resultado do Tratamento
4.
Neurol Clin ; 39(1): 209-229, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33223084

RESUMO

Botulinum neurotoxin (BoNT) is an effective treatment for many neurologic disorders. This article gives a comprehensive overview of the clinical applications of BoNT across the field of neurology.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Humanos , Neurologia/métodos , Resultado do Tratamento
5.
Emerg Med Clin North Am ; 39(1): 133-154, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33218654

RESUMO

Management of acute neurologic disorders in the emergency department is multimodal and may require the use of medications to decrease morbidity and mortality secondary to neurologic injury. Clinicians should form an individualized treatment approach with regard to various patient specific factors. This review article focuses on the pharmacotherapy for common neurologic emergencies that present to the emergency department, including traumatic brain injury, central nervous system infections, status epilepticus, hypertensive emergencies, spinal cord injury, and neurogenic shock.


Assuntos
Serviço Hospitalar de Emergência , Doenças do Sistema Nervoso/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Emergências , Humanos , Pressão Intracraniana/efeitos dos fármacos , Neurofarmacologia , Estado Epiléptico/tratamento farmacológico
6.
Adv Exp Med Biol ; 1264: 47-65, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33332003

RESUMO

In recent years, an increasing number of investigations has demonstrated the therapeutic potential of molecules targeting the endocannabinoid system. Cannabinoids of endogenous, phytogenic, and synthetic nature have been assessed in a wide variety of disease models ranging from neurological to metabolic disorders. Even though very few compounds of this type have already reached the market, numerous preclinical and clinical studies suggest that cannabinoids are suitable drugs for the clinical management of diverse pathologies.In this chapter, we will provide an overview of the endocannabinoid system under certain physiopathological conditions, with a focus on neurological, oncologic, and metabolic disorders. Cannabinoids evaluated as potential therapeutic agents in experimental models with an emphasis in the most successful chemical entities and their perspectives towards the clinic will be discussed.


Assuntos
Canabinoides/síntese química , Canabinoides/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Canabinoides/metabolismo , Endocanabinoides/metabolismo , Humanos , Doenças Metabólicas/metabolismo , Modelos Biológicos , Neoplasias/metabolismo , Doenças do Sistema Nervoso/metabolismo
8.
Int J Mol Sci ; 21(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33333772

RESUMO

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.


Assuntos
Amidas/administração & dosagem , Amidas/metabolismo , Etanolaminas/administração & dosagem , Etanolaminas/metabolismo , Inflamação/dietoterapia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/metabolismo , Doença de Alzheimer/dietoterapia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Esclerose Amiotrófica Lateral/dietoterapia , Esclerose Amiotrófica Lateral/tratamento farmacológico , Esclerose Amiotrófica Lateral/metabolismo , Animais , Transtorno do Espectro Autista/dietoterapia , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/metabolismo , Endocanabinoides/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Redes e Vias Metabólicas , Esclerose Múltipla/dietoterapia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Doenças do Sistema Nervoso/dietoterapia , Doenças do Sistema Nervoso/metabolismo , Doenças Neurodegenerativas/dietoterapia , Doenças Neurodegenerativas/metabolismo , Dor/dietoterapia , Dor/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
9.
Int J Mol Sci ; 21(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353225

RESUMO

The class of tetrapyrrol "coordination complexes" called hemes are prosthetic group components of metalloproteins including hemoglobin, which provide functionality to these physiologically essential macromolecules by reversibly binding diatomic gasses, notably O2, which complexes to ferrous (reduced/Fe(II)) iron within the heme porphyrin ring of hemoglobin in a pH- and PCO2-dependent manner-thus allowing their transport and delivery to anatomic sites of their function. Here, pathologies associated with aberrant heme degradation are explored in the context of their underlying mechanisms and emerging medical countermeasures developed using heme oxygenase (HO), its major degradative enzyme and bioactive metabolites produced by HO activity. Tissue deposits of heme accumulate as a result of the removal of senescent or damaged erythrocytes from circulation by splenic macrophages, which destroy the cells and internal proteins, including hemoglobin, leaving free heme to accumulate, posing a significant toxicogenic challenge. In humans, HO uses NADPH as a reducing agent, along with molecular oxygen, to degrade heme into carbon monoxide (CO), free ferrous iron (FeII), which is sequestered by ferritin protein, and biliverdin, subsequently metabolized to bilirubin, a potent inhibitor of oxidative stress-mediated tissue damage. CO acts as a cellular messenger and augments vasodilation. Nevertheless, disease- or trauma-associated oxidative stressors sufficiently intense to overwhelm HO may trigger or exacerbate a wide range of diseases, including cardiovascular and neurologic syndromes. Here, strategies are described for counteracting the effects of aberrant heme degradation, with a particular focus on "bioflavonoids" as HO inducers, shown to cause amelioration of severe inflammatory diseases.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia , Flavonoides/farmacologia , Heme/metabolismo , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Animais , Heme Oxigenase-1/metabolismo , Humanos
10.
Nature ; 585(7826): 614-619, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32879484

RESUMO

Tropane alkaloids from nightshade plants are neurotransmitter inhibitors that are used for treating neuromuscular disorders and are classified as essential medicines by the World Health Organization1,2. Challenges in global supplies have resulted in frequent shortages of these drugs3,4. Further vulnerabilities in supply chains have been revealed by events such as the Australian wildfires5 and the COVID-19 pandemic6. Rapidly deployable production strategies that are robust to environmental and socioeconomic upheaval7,8 are needed. Here we engineered baker's yeast to produce the medicinal alkaloids hyoscyamine and scopolamine, starting from simple sugars and amino acids. We combined functional genomics to identify a missing pathway enzyme, protein engineering to enable the functional expression of an acyltransferase via trafficking to the vacuole, heterologous transporters to facilitate intracellular routing, and strain optimization to improve titres. Our integrated system positions more than twenty proteins adapted from yeast, bacteria, plants and animals across six sub-cellular locations to recapitulate the spatial organization of tropane alkaloid biosynthesis in plants. Microbial biosynthesis platforms can facilitate the discovery of tropane alkaloid derivatives as new therapeutic agents for neurological disease and, once scaled, enable robust and agile supply of these essential medicines.


Assuntos
Alcaloides/biossíntese , Alcaloides/provisão & distribução , Hiosciamina/biossíntese , Saccharomyces cerevisiae/metabolismo , Escopolamina/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Animais , Atropa belladonna/enzimologia , Derivados da Atropina/metabolismo , Transporte Biológico , Datura/enzimologia , Glucosídeos/biossíntese , Glucosídeos/metabolismo , Hiosciamina/provisão & distribução , Lactatos/metabolismo , Ligases/genética , Ligases/metabolismo , Modelos Moleculares , Doenças do Sistema Nervoso/tratamento farmacológico , Oxirredutases/genética , Oxirredutases/metabolismo , Engenharia de Proteínas , Saccharomyces cerevisiae/genética , Escopolamina/provisão & distribução , Vacúolos/metabolismo
11.
Curr Opin Anaesthesiol ; 33(5): 655-660, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32826628

RESUMO

PURPOSE OF REVIEW: The current systematic review summarizes recent, basic clinical achievements regarding the neuroprotective effects of molecular hydrogen in distinct central nervous system conditions. RECENT FINDINGS: Perioperative neuroprotection remains a major topic of clinical anesthesia. Various gaseous molecules have previously been explored as a feasible therapeutic option in neurological disorders. Among them, molecular hydrogen, which has emerged as a novel and potential therapy for perioperative neuroprotection, has received much attention. SUMMARY: Fundamental and clinical evidence supports the antioxidant, antiinflammation, antiapoptosis and mitochondrial protective effects of hydrogen in the pathophysiology of nervous system diseases. The clinically preventive and therapeutic effects of hydrogen on different neural diseases, however, remain uncertain, and the lack of support by large randomized controlled trials has delayed its clinical application.


Assuntos
Hidrogênio/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Assistência Perioperatória/métodos , Humanos , Período Perioperatório , Complicações Pós-Operatórias/prevenção & controle
12.
J Neuroophthalmol ; 40(3): 305-314, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32804456

RESUMO

The initiation and continuation of immune-based therapies to treat and prevent complications of inflammatory neuro-ophthalmologic disorders during the 2019 novel coronavirus (COVID-19) pandemic is the subject of considerable debate. In each case, a treatment decision must be reached based on best clinical practices for the disorder, patient comorbidities, the current state of knowledge about the pathogenesis and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the utilization of hospital and community resources. Unfortunately, the evidence needed to standardize the decision-making process for each neuro-ophthalmologic disorder is currently absent and is likely to require months or years to develop based on the accrual of robust international data sets. In this article, we review the current understanding of SARS-CoV-2 and COVID-19 complications to provide a framework for approaching the treatment of inflammatory neuro-ophthalmic disorders during the COVID-19 viral pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Oftalmopatias/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , Infecções por Coronavirus/imunologia , Arterite de Células Gigantes/tratamento farmacológico , Humanos , Imunomodulação , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Neurite Óptica/tratamento farmacológico , Pneumonia Viral/imunologia
13.
Rinsho Shinkeigaku ; 60(9): 631-635, 2020 Sep 29.
Artigo em Japonês | MEDLINE | ID: mdl-32779602

RESUMO

We report a 62-year-old female with rheumatoid meningitis. She presented with mental disorder, loss of consciousness, generalized seizures, and cognitive impairment. Brain MRI demonstrated high intensity lesions and abnormal enhancement along the left frontal and parietal sulci. Her serum and cerebrospinal fluid were positive for anti-cyclic citrullinated peptides (CCP) antibody, and the antibody index of cerebrospinal fluid anti-CCP antibody increased, which led us to suspect rheumatoid meningitis. Her symptoms improved immediately by methylpredonisolone pulse therapy and anti-CCP antibody turned negative in cerebrospinal fluid. However, she revealed arthritis with the reduction of betamethasone and was diagnosed as rheumatoid arthritis. We suggest that the elevation of antibody index of cerebrospinal fluid anti-CCP antibody is useful in the diagnosis of rheumatoid meningitis preceding neurological symptoms without arthritis, and anti-CCP antibody in cerebrospinal fluid may be helpful as the evaluation of the treatment.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Autoanticorpos/líquido cefalorraquidiano , Meningite/diagnóstico , Meningite/etiologia , Doenças do Sistema Nervoso/etiologia , Peptídeos Cíclicos/imunologia , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Meningite/tratamento farmacológico , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/tratamento farmacológico , Pulsoterapia , Resultado do Tratamento
14.
Life Sci ; 260: 118182, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781063

RESUMO

BACKGROUND: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more. AIM: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases. METHOD: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs. KEY FINDINGS: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties. SIGNIFICANCE: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases.


Assuntos
Doença Crônica/tratamento farmacológico , Diosgenina/uso terapêutico , Animais , Disponibilidade Biológica , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Fenômenos Químicos , Doença Crônica/prevenção & controle , Diosgenina/análogos & derivados , Diosgenina/farmacocinética , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Fitoterapia , PubMed , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Trigonella
16.
Brain ; 143(10): 3104-3120, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32637987

RESUMO

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.


Assuntos
Infecções por Coronavirus , Doenças do Sistema Nervoso , Pandemias , Pneumonia Viral , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Londres/epidemiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Adulto Jovem
17.
Immunol Med ; 43(4): 135-141, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32459601

RESUMO

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by diverse organ damages resulting from various autoantibodies, such as antinuclear or anti-DNA antibodies. Neuropsychiatric lupus (NPSLE) refers to the neurological and psychiatric disorders complicated with SLE and can be challenging for physicians to manage. NPSLE has a broad spectrum and high heterogeneity of clinical phenotypes, including headaches, psychiatric symptoms and peripheral neuropathy. Additionally, various immune effectors have been reported to contribute to the pathogenesis, including cytokines, cell-mediated inflammation and brain-reactive autoantibodies. In some patients with SLE, neuropsychiatric symptoms develop for the first time after the initiation of the steroid treatment, hindering the differentiation from steroid psychosis. The administration of high doses of steroids in patients with SLE is believed to trigger psychiatric symptoms. No clear evidence has yet been found regarding the treatment of NPSLE. Therefore, NPSLE-specific markers need to be developed, and treatment guidelines should be established. This article provides an overview of NPSLE as well as its pathogenesis and treatment.


Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Anticorpos Antinucleares , Autoanticorpos , Citocinas/líquido cefalorraquidiano , Humanos , Hidroxicloroquina/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/imunologia , Ácido Micofenólico/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/imunologia , Rituximab/uso terapêutico
19.
Neurocrit Care ; 32(3): 667-671, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32346843

RESUMO

The magnitude of the COVID-19 pandemic will result in substantial neurological disease, whether through direct infection (rare), para-infectious complications (less rare), or critical illness more generally (common). Here, we raise the importance of stringent diagnosis and data collection regarding neurological complications of COVID-19; we urge caution in the over-diagnosis of neurological disease where it does not exist, but equally strongly encourage the concerted surveillance for such conditions. Additional to the direct neurological complications of COVID-19 infection, neurological patients are at risk of harm from both structural limitations (such as number of intensive care beds), and a hesitancy to treat with certain necessary medications given risk of nosocomial COVID-19 infection. We therefore also outline the specific management of patients with neuroinflammatory diseases in the context of the pandemic. This article describes the implications of COVID-19 on neurological disease and advertises the Neurocritical Care Society's international data collection collaborative that seeks to align data elements.


Assuntos
Infecções por Coronavirus/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Disfunção Cognitiva/etiologia , Infecções por Coronavirus/complicações , Cuidados Críticos , Estado Terminal , Infecção Hospitalar/prevenção & controle , Coleta de Dados , Encefalomielite Aguda Disseminada/etiologia , Síndrome de Guillain-Barré/etiologia , Humanos , Imunossupressores/efeitos adversos , Controle de Infecções , Cooperação Internacional , Mielite Transversa/etiologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Pandemias , Pneumonia Viral/complicações
20.
Eur J Med Chem ; 194: 112242, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32248004

RESUMO

N-Methyl-d-aspartate receptors (NMDARs) are crucial for the normal function of the central nervous system (CNS), and fundamental in memory and learning-related processes. The overactivation of these receptors is associated with numerous neurodegenerative and psychiatric disorders. Therefore, NMDAR is considered a relevant therapeutic target for many CNS disorders. Herein, we report the synthesis and pharmacological evaluation of a new scaffold with antagonistic activity for NMDAR. Specifically, a chemical library of eighteen 1-aminoindan-2-ol tetracyclic lactams was synthesized and screened as NMDAR antagonists. The compounds were obtained by chiral pool synthesis using enantiomerically pure 1-aminoindan-2-ols as chiral inductors, and their stereochemistry was proven by X-ray crystallographic analysis of two target compounds. Most compounds reveal NMDAR antagonism, and eleven compounds display IC50 values in a Ca2+ entry-sensitive fluo-4 assay in the same order of magnitude of memantine, a clinically approved NMDAR antagonist. Docking studies suggest that the novel compounds can act as NMDAR channel blockers since there is a compatible conformation with MK-801 co-crystallized with NMDAR channel. In addition, we show that the tetracyclic 1-aminoindan-2-ol derivatives are brain permeable and non-toxic, and we identify promising hits for further optimization as modulators of the NMDAR function.


Assuntos
Lactamas/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Barreira Hematoencefálica/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células HEK293 , Células Hep G2 , Humanos , Lactamas/síntese química , Lactamas/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Doenças do Sistema Nervoso/metabolismo , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Receptores de N-Metil-D-Aspartato/metabolismo , Relação Estrutura-Atividade
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