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1.
BMJ Open ; 11(5): e046948, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33980528

RESUMO

INTRODUCTION: The pupillary examination is an important part of the neurological assessment, especially in the setting of acutely brain-injured patients, and pupillary abnormalities are associated with poor outcomes. Currently, the pupillary examination is based on a visual, subjective and frequently inaccurate estimation. The use of automated infrared pupillometry to measure the pupillary light reflex can precisely quantify subtle changes in pupillary functions. The study aimed to evaluate the association between abnormal pupillary function, assessed by the Neurological Pupil Index (NPi), and long-term outcomes in patients with acute brain injury (ABI). METHODS AND ANALYSIS: The Outcome Prognostication of Acute Brain Injury using the Neurological Pupil Index study is a prospective, observational study including adult patients with ABI requiring admission at the intensive care unit. We aimed to recruit at least 420 patients including those suffering from traumatic brain injury or haemorrhagic strokes, over 12 months. The primary aim was to assess the relationship between NPi and 6-month mortality or poor neurological outcome, measured by the Extended Glasgow Outcome Score (GOS-E, poor outcome=GOS-E 1-4). Supervised and unsupervised methods and latent class mixed models will be used to identify patterns of NPi trajectories and Cox and logistic model to evaluate their association with outcome. ETHICS AND DISSEMINATION: The study has been approved by the institutional review board (Comitato Etico Brianza) on 16 July 2020. Approved protocol V.4.0 dated 10 March 2020. The results of this study will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04490005.


Assuntos
Lesões Encefálicas , Pupila , Adulto , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico , Estudos de Coortes , Humanos , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos Prospectivos , Reflexo Pupilar
2.
Lancet Neurol ; 20(6): 460-469, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34022171

RESUMO

Post-traumatic headache is a common sequela of traumatic brain injury and is classified as a secondary headache disorder. In the past 10 years, considerable progress has been made to better understand the clinical features of this disorder, generating momentum to identify effective therapies. Post-traumatic headache is increasingly being recognised as a heterogeneous headache disorder, with patients often classified into subphenotypes that might be more responsive to specific therapies. Such considerations are not accounted for in three iterations of diagnostic criteria published by the International Headache Society. The scarcity of evidence-based approaches has left clinicians to choose therapies on the basis of the primary headache phenotype (eg, migraine and tension-type headache) and that are most compatible with the clinical picture. A concerted effort is needed to address these shortcomings and should include large prospective cohort studies as well as randomised controlled trials. This approach, in turn, will result in better disease characterisation and availability of evidence-based treatment options.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Cefaleia Pós-Traumática/classificação , Cefaleia Pós-Traumática/terapia , Lesões Encefálicas/complicações , Lesões Encefálicas Traumáticas/classificação , Lesões Encefálicas Traumáticas/fisiopatologia , Progressão da Doença , Cefaleia , Transtornos da Cefaleia , Transtornos da Cefaleia Secundários/classificação , Transtornos da Cefaleia Secundários/etiologia , Humanos , Transtornos de Enxaqueca , Cefaleia Pós-Traumática/fisiopatologia , Estudos Prospectivos , Cefaleia do Tipo Tensional
3.
Acta Neurochir Suppl ; 131: 71-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33839821

RESUMO

Hyperthermia is a common detrimental condition in patients with an acute brain injury (ABI), which can worsen their prognosis and outcome. The aim of this study was to evaluate the effects of hyperthermia on intracranial pressure (ICP) and cerebral autoregulation (CA).Eight patients with ABI were studied. CA was assessed on the basis of the pressure reactivity index (PRx) coefficient. The ICP, cerebral perfusion pressure (CPP), and PRx were compared before and during development of hyperthermia. Hyperthermia was defined as an increase in cerebral temperature above 38.3 °C.Thirty-three episodes of hyperthermia were analyzed: 25 of these occurred on a background of initially normal ICP whereas 8 occurred on a background of initially elevated ICP, and 17 of the 33 episodes occurred on a background of initially intact autoregulation whereas 16 occurred on a background of initially impaired autoregulation.During hyperthermia, elevated ICP was found in 52% of instances where it was initially normal, and further progression of intracranial hypertension occurred in 100% of instances where ICP was initially elevated. The median ICP during hyperthermia was 24 [range quartiles 22-28] mmHg in instances where it was initially normal and 31 [quartiles 27-32] mmHg in instances where it was initially elevated (p < 0.01). The correlation coefficient between the brain temperature and ICP was 0.11 (p < 0.01). During hyperthermia, the number of episodes of ICP >20 mmHg increased by 41% in instances with intact autoregulation but ICP was above 20 mmHg and by 38% (p > 0.05) in instances with impaired autoregulation and ICP was 20 mmHg. The cerebral hyperthermia-associated increase in ICP was not associated with impaired autoregulation.


Assuntos
Lesões Encefálicas , Hipertensão Intracraniana , Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Circulação Cerebrovascular , Homeostase , Humanos , Hipertermia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/terapia , Pressão Intracraniana
4.
Int J Mol Sci ; 22(8)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920986

RESUMO

Amyloidoses are a group of diseases associated with the formation of pathological protein fibrils with cross-ß structures. Approximately 5-10% of the cases of these diseases are determined by amyloidogenic mutations, as well as by transmission of infectious amyloids (prions) between organisms. The most common group of so-called sporadic amyloidoses is associated with abnormal aggregation of wild-type proteins. Some sporadic amyloidoses are known to be induced only against the background of certain pathologies, but in some cases the cause of amyloidosis is unclear. It is assumed that these diseases often occur by accident. Here we present facts and hypotheses about the association of sporadic amyloidoses with vascular pathologies, trauma, oxidative stress, cancer, metabolic diseases, chronic infections and COVID-19. Generalization of current data shows that all sporadic amyloidoses can be regarded as a secondary event occurring against the background of diseases provoking a cellular stress response. Various factors causing the stress response provoke protein overproduction, a local increase in the concentration or modifications, which contributes to amyloidogenesis. Progress in the treatment of vascular, metabolic and infectious diseases, as well as cancers, should lead to a significant reduction in the risk of sporadic amyloidoses.


Assuntos
Amiloidose/etiologia , Estresse Fisiológico , Lesões Encefálicas/complicações , Doenças Transmissíveis/complicações , Humanos , Doenças Metabólicas/complicações , Neoplasias/complicações , Estresse Oxidativo , Doenças Vasculares/complicações
5.
J Clin Neurosci ; 87: 69-73, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863537

RESUMO

Eyelid closing or opening disorders have been only sporadically described in patients with focal brain lesions over the last decades. Furthermore, the restricted number of reports and the lack of uniform clinical assessment of affected individuals did not allow to define more in depth the clinical features and the underlying neural correlates of these uncommon clinical disorders. Here we report an 89-years old woman with a right hemispheric lesion who showed a contralesional defect of eyelid closure. We also include a video neuroimage of this case and a review of eyelid closing and opening disorders in patients with focal unilateral lesions. In this review we found a correlation between right hemisphere and eyelid motor control, particularly for apraxia of eyelid closure affecting only the contralesional eye. The right parietal lobe was most frequently affected in this unilateral form of eyelid closing disorders, whereas putamen and other subcortical structures were more involved in eyelid opening than in eyelid closing disorders. The relations between unilateral eyelid closing disorders and other forms of motor-intentional defects are shortly discussed.


Assuntos
Lesões Encefálicas/complicações , Doenças Palpebrais/etiologia , Pálpebras/patologia , Idoso , Idoso de 80 Anos ou mais , Apraxias/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/lesões
6.
Int J Mol Sci ; 22(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924540

RESUMO

Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits. This review provides an overview of the neonatal immunity, neuroinflammation, and mechanisms of inflammation-related brain injury in preterm infants and explores the safety and efficacy of anti-inflammatory agents as potentially neurotherapeutics.


Assuntos
Anti-Inflamatórios/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Inflamação/tratamento farmacológico , Lesões Encefálicas/complicações , Lesões Encefálicas/imunologia , Citocinas/metabolismo , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Inflamação/complicações , Modelos Biológicos
7.
Hipertens. riesgo vasc ; 38(1): 44-47, ene.-mar. 2021. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-202412

RESUMO

Presentamos el caso de un paciente de 34 años que sufre un traumatismo craneoencefálico grave con afectación cerebral severa. Evoluciona de manera tórpida precisando varias reintervenciones por sangrado y herniación de masa encefálica. Nos interconsultan desde Neurocirugía por irregular control de cifras de presión arterial a pesar de tratamiento con calcioantagonistas. El paciente asocia diaforesis, taquipnea y taquicardia, junto a fiebre de alto grado de forma persistente sin evidencia microbiológica. Analítica con función renal normal, sin proteinuria y sin datos de hipertrofia de ventrículo izquierdo que sugieran hipertensión arterial previa. Esto nos hace plantearnos como primera posibilidad diagnóstica un síndrome de hiperactividad simpática debido al daño neurológico severo. Se inicia terapia antihipertensiva orientada a esta sospecha, entre los que se incluyen betabloqueantes no cardioselectivos, alfa-2-agonistas, benzodiacepinas y agonistas de los receptores GABA. Así se consigue mejorar la labilidad de las cifras de presión arterial, lo que apoya el diagnóstico


We present the case of a 34-year-old patient with severe head trauma and severe brain involvement. The patient deteriorated progressively and required several reinterventions for bleeding and brain herniation. We were consulted by neurosurgery due to irregular blood pressure control despite treatment with calcium antagonists. The patient had associated diaphoresis, tachypnoea and tachycardia, together with persistent high-grade fever with no microbiological evidence. Laboratory tests showed normal kidney function, with no proteinuria and no signs of left ventricular hypertrophy to suggest previous arterial hypertension. This led us to consider sympathetic hyperactivity syndrome as a first possible diagnosis due to severe neurological damage. In line with this suspicion, antihypertensive therapy was initiated which included non-cardioselective beta-blockers, alpha-2 agonists, benzodiazepines and GABA receptor agonists. Thus, we were able to improve the labile blood pressure levels, which supports the diagnosis


Assuntos
Humanos , Masculino , Adulto , Traumatismos Cranianos Penetrantes/complicações , Hipertensão/etiologia , Pressão Arterial/efeitos dos fármacos , Hematoma Epidural Craniano/diagnóstico por imagem , Sistema Nervoso Simpático/fisiopatologia , Lesões Encefálicas/complicações , Traumatismos Cranianos Penetrantes/cirurgia , Taquipneia/complicações , Taquicardia/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , Doenças do Sistema Nervoso Central/etiologia
8.
J Craniofac Surg ; 32(2): 458-460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704959

RESUMO

INTRODUCTION: Dysarthria is one of the commonest neurological speech disorders resulting from brain injury. However, hypernasality commonly co-exists in this subgroup of patients and is commonly overlooked. The authors aim to investigate the merit of surgery in improving hypernasality and speech intelligibility in patients with a mixed pattern of dysarthria and hypernasality secondary to brain injury. MATERIALS AND METHODS: Data was collected from the regional plastic surgery unit over a 10-year period. All patients who underwent a pharyngoplasty for speech improvement following total brain injury from either a traumatic injury or a cerebrovascular accident were included. Patients were followed up post-operatively to assess; improvement in speech rehabilitation, complications and the need for surgical revision. RESULTS: Six patients had a pharyngoplasty for speech improvement. Either a Hynes or Jackson pharyngoplasty was performed, with one patient requiring a hemi-pharyngoplasty. Post-operatively, 1 patient experienced self-limiting sleep apnea which resolved within 1 month. One patient developed obstructive symptoms and required revision. Overall, 83% of patients had clear improvement in speech intelligibility and articulation. CONCLUSIONS: The authors have shown that surgical intervention, in the form of a pharyngoplasty, is an effective method of improving speech intelligibility and articulation, by improving hypernasality and restoring communication in this cohort of patients. The aim of this paper is to highlight this option to colleagues and to heighten the awareness that many patients with a total brain injury have a mixed pattern of speech disturbance and not solely the dysarthria that is attributed to this condition.


Assuntos
Lesões Encefálicas , Insuficiência Velofaríngea , Lesões Encefálicas/complicações , Lesões Encefálicas/cirurgia , Humanos , Faringe , Fala , Distúrbios da Fala/etiologia , Distúrbios da Fala/cirurgia , Inteligibilidade da Fala , Resultado do Tratamento , Insuficiência Velofaríngea/etiologia , Insuficiência Velofaríngea/cirurgia
9.
BMC Neurol ; 21(1): 133, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33752631

RESUMO

BACKGROUND: Prolonged disorders of consciousness (PDOC) are amongst the severest sequelae of acquired brain injury. Evidence regarding epidemiology and rehabilitation outcomes is scarce. These knowledge gaps and psychological distress in families of PDOC patients may complicate clinical decision-making. The complex PDOC care and associated moral dilemmas result in high workload in healthcare professionals. Since 2019, all PDOC patients in the Netherlands have access to intensive neurorehabilitation up to 2 years post-injury provided by one rehabilitation center and four specialized nursing homes. Systematic monitoring of quantitative rehabilitation data within this novel chain of care is done in a study called DOCTOR. The optimization of tailored PDOC care, however, demands a better understanding of the impact of PDOC on patients, their families and healthcare professionals and their views on rehabilitation outcomes, end-of-life decisions and quality of dying. The True Outcomes of PDOC (TOPDOC) study aims to gain insight in the qualitative outcomes of PDOC rehabilitation and impact of PDOC on patients, their families and healthcare professionals. METHODS: Nationwide multicenter prospective cohort study in the settings of early and prolonged intensive neurorehabilitation with a two-year follow-up period, involving three study populations: PDOC patients > 16 years, patients' family members and healthcare professionals involved in PDOC care. Families' and healthcare professionals' views on quality of rehabilitation outcomes, end-of-life decisions and dying will be qualitatively assessed using comprehensive questionnaires and in-depth interviews. Ethical dilemmas will be explored by studying moral deliberations. The impact of providing care to PDOC patients on healthcare professionals will be studied in focus groups. DISCUSSION: To our knowledge, this is the first nationwide study exploring quality of outcomes, end-of-life decisions and dying in PDOC patients and the impact of PDOC in a novel chain of care spanning the first 24 months post-injury in specialized rehabilitation and nursing home settings. Newly acquired knowledge in TOPDOC concerning quality of outcomes in PDOC rehabilitation, ethical aspects and the impact of PDOC will enrich quantitative epidemiological knowledge and outcomes arising from DOCTOR. Together, these projects will contribute to the optimization of centralized PDOC care providing support to PDOC patients, families and healthcare professionals.


Assuntos
Lesões Encefálicas/complicações , Transtornos da Consciência/reabilitação , Reabilitação Neurológica , Sistema de Registros , Assistência Terminal/ética , Estado de Consciência , Transtornos da Consciência/etiologia , Família/psicologia , Pessoal de Saúde/psicologia , Humanos , Países Baixos , Estudos Prospectivos , Inquéritos e Questionários , Assistência Terminal/psicologia
10.
Oxid Med Cell Longev ; 2021: 6632411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603949

RESUMO

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.


Assuntos
AVC Isquêmico/complicações , Azul de Metileno/farmacologia , Substância Branca/lesões , Animais , Apoptose/efeitos dos fármacos , Gânglios da Base/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Córtex Cerebral/patologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Infarto da Artéria Cerebral Média/complicações , Masculino , Azul de Metileno/administração & dosagem , Azul de Metileno/uso terapêutico , Camundongos , Atividade Motora/efeitos dos fármacos , Bainha de Mielina/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos Sprague-Dawley , Trombose/complicações , Trombose/patologia , Substância Branca/efeitos dos fármacos , Substância Branca/patologia
12.
Brain Inj ; 35(5): 520-529, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33587672

RESUMO

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI.Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected.Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen.Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities.


Assuntos
Lesões Encefálicas/complicações , COVID-19/complicações , Transtornos da Consciência/complicações , Lesões Encefálicas/virologia , Teste para COVID-19 , Transtornos da Consciência/virologia , Humanos , Itália
13.
BMC Neurol ; 21(1): 69, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579219

RESUMO

BACKGROUND: Prolonged disorders of consciousness (PDOC) may occur after severe brain injury. Two diagnostic entities are distinguished within PDOC: unresponsive wakefulness syndrome (UWS, previously known as vegetative state) and minimally conscious state (MCS). Patients with PDOC may benefit from early intensive neurorehabilitation (EIN). In the Netherlands, the EIN programme is provided by one designated expert rehabilitation centre and forms the starting point of a dedicated chain of specialised rehabilitation and care for this group. This study project, called DOCTOR: Disorders of Consciousness; Treatment and Outcomes Registry, sets up a registry and systematically investigates multiple short- and long-term outcomes of patients with PDOC who receive EIN. METHODS: Single-centre prospective cohort study with a 2-year follow-up period. Patients with PDOC due to acute brain injury who receive EIN, aged 16 years and older are included. Measurements will take place at start EIN, in week 5, 10, and at discharge from the EIN programme (duration = max 14 weeks) and at week 28, 40, 52, and 104 after admission to the EIN programme, following patients through the health-care chain. Outcome measures are the changes over time in level of consciousness, using the Coma Recovery Scale-Revised; the frequency and type of medical complications; the mortality rate; level of disability, including the level of motor, cognitive, behavioural and emotional functioning; participation; and quality of life. Secondary outcomes include self-efficacy of caregivers, caregivers' strain and cost-effectiveness of the programme. DISCUSSION: The DOCTOR study will provide insight in the recovery patterns and predictors of recovery for multiple outcomes in PDOC patients after following EIN. The results of the study will enable us to benchmark and improve EIN and the organisation of the health-care chain, both for patients with PDOC and for their families. TRIAL REGISTRATION: Netherlands Trial Register, NL 8138 . Retrospectively registered 6 November 2019.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/reabilitação , Transtornos da Consciência/reabilitação , Reabilitação Neurológica/métodos , Resultado do Tratamento , Adolescente , Adulto , Transtornos da Consciência/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Prognóstico , Estudos Prospectivos , Qualidade de Vida
14.
Am J Phys Med Rehabil ; 100(3): 266-270, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33595939

RESUMO

OBJECTIVE: The aim of this study was to explore the time course of onset and peak effects of phenol neurolysis. DESIGN: This is a retrospective chart review. Eleven patients with elbow flexor spasticity after brain injury were enrolled. The resting angle of the elbow joint was measured before and after the injection and up to 6 wks of follow-up. RESULTS: Phenol injection was performed to 13 musculocutaneous nerves under ultrasound and electrical stimulation guidance. The resting elbow angles were 84.4° ± 25.8° (before injection), 116.6° ± 20.9° (immediately after injection), 121.2° ± 21.4° (2 hrs after injection), 127.2° ± 19.7° (24 hrs after injection), 145.4° ± 11.8° (7 days after injection), 145.5° ± 10.4° (14 days after injection), and 150.3° ± 12.2° (6 wks after injection; N = 7). The mean resting angle was statistically different among the time points from preinjection to 14 days after (F2.625, 31.505 = 36.805, P < 0.01). Post hoc tests revealed that significant improvements existed immediately after and 7 days after the injection (P < 0.01 for both). The effects seemed to reach its peak in 7 days. The effect sizes immediately and 7 days after the injection were 1.37 and 3.04, respectively. The immediate effect accounted for approximately 60% of the maximal effect. CONCLUSIONS: Phenol neurolysis has an immediate effect on spasticity reduction and reaches its peak effect around 1 wk after injection.


Assuntos
Articulação do Cotovelo/fisiopatologia , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/fisiopatologia , Nervo Musculocutâneo/efeitos dos fármacos , Bloqueio Nervoso/métodos , Fenóis/administração & dosagem , Adulto , Lesões Encefálicas/complicações , Estudos de Coortes , Feminino , Humanos , Injeções Subcutâneas , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Tempo
15.
Expert Opin Pharmacother ; 22(8): 1025-1037, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33467932

RESUMO

Introduction: Cerebral edema is a common complication of multiple neurological diseases and is a strong predictor of outcome, especially in traumatic brain injury and large hemispheric infarction.Areas Covered: Traditional and current treatments of cerebral edema include treatment with osmotherapy or decompressive craniectomy at the time of clinical deterioration. The authors discuss preclinical and clinical models of a variety of neurological disease states that have identified receptors, ion transporters, and channels involved in the development of cerebral edema as well as modulation of these receptors with promising agents.Expert opinion: Further study is needed on the safety and efficacy of the agents discussed. IV glibenclamide has shown promise in preclinical and clinical trials of cerebral edema in large hemispheric infarct and traumatic brain injury. Consideration of underlying pathophysiology and pharmacodynamics is vital, as the synergistic use of agents has the potential to drastically mitigate cerebral edema and secondary brain injury thusly transforming our treatment paradigms.


Assuntos
Edema Encefálico , Lesões Encefálicas , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Humanos
16.
Biofactors ; 47(2): 190-197, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33098588

RESUMO

Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID-19). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , COVID-19/tratamento farmacológico , Inflamação/tratamento farmacológico , Luteolina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/virologia , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/virologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/virologia , COVID-19/complicações , COVID-19/virologia , Flavonas/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/virologia , Neurônios/efeitos dos fármacos , Neurônios/virologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade
17.
Mil Med ; 186(3-4): e393-e400, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33135742

RESUMO

INTRODUCTION: We assessed the utility of a battery of neuropsychological, neurocognitive, physiological (balance, ataxia, postural tremor), and neuroimaging measures for studying the effects of blast waves in breachers-a population repeatedly exposed to low-level blast during military training and operations. MATERIALS AND METHODS: Data were collected from four nonoverlapping samples, in the course of similarly structured 4-day breacher training exercises in successive years involving a combination of indoor and outdoor blast events. In all cases, self-report and neuropsychological measures were administered once at baseline (i.e., 1 day before the start of training). In years 1-2, neurocognitive and physiological measures were administered daily before and after training. In years 3-4, neurocognitive data were collected once at baseline. In Year 4, we introduced 3 modifications to our design. First, in addition to breachers, we also collected data from sex-and age-matched military controls at the same time points. Second, we assessed balance, ataxia, and postural tremor immediately following blast exposure "in the field," enabling us to quantify its acute effects. Third, structural magnetic resonance imaging (MRI) scans were acquired before and after the 4-day training exercise to explore differences between breachers and controls at baseline, as well as possible training-related changes using voxel-based morphometry. These design modifications were made to enable us to test additional hypotheses in the context of the same training exercise. RESULTS: At baseline, scores on the "Rivermead Post Concussion Symptoms Questionnaire," "RAND SF-36" (physical functioning, role limitation due to physical health, social functioning, energy/fatigue, general health), and "Short Musculoskeletal Function Questionnaire" distinguished breachers from controls. Also at baseline, the MRI data revealed that there was greater regional gray matter volume in controls compared to breachers in the right superior frontal gyrus. Balance, ataxia, and postural tremor did not exhibit sensitivity to the acute effects of blast in the field, nor did neurocognitive measures to its cumulative or daily effects. CONCLUSION: Our exploratory results suggest that self-report neuropsychological measures and structural MRI hold promise as sensitive measures for quantifying the long-term, cumulative effects of blast exposure in breachers. We discuss the limitations of our study and the need for prospective longitudinal data for drawing causal inferences regarding the impact of blast exposure on breachers' health and performance.


Assuntos
Traumatismos por Explosões/diagnóstico por imagem , Lesões Encefálicas/diagnóstico , Explosões , Militares/psicologia , Neuroimagem/métodos , Doenças Vestibulares/diagnóstico , Testes de Função Vestibular/métodos , Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico , Traumatismos por Explosões/fisiopatologia , Lesões Encefálicas/complicações , Canadá , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Estudos Prospectivos , Doenças Vestibulares/etiologia
18.
Resuscitation ; 158: 253-257, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33127439

RESUMO

AIM: To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells. METHODS: Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome. RESULTS: 128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p < 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest. CONCLUSION: ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.


Assuntos
Lesões Encefálicas , Estado Epiléptico , Biomarcadores , Lesões Encefálicas/complicações , Eletroencefalografia , Proteína Glial Fibrilar Ácida , Humanos , Estado Epiléptico/diagnóstico , Estado Epiléptico/etiologia
19.
Br J Anaesth ; 126(2): 467-476, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33183737

RESUMO

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid ß (Aß1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aß1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aß1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.


Assuntos
Amiloidose/líquido cefalorraquidiano , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Biomarcadores/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Complicações Cognitivas Pós-Operatórias/etiologia , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Amiloidose/complicações , Amiloidose/diagnóstico , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico , Cognição , Feminino , Humanos , Masculino , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Complicações Cognitivas Pós-Operatórias/líquido cefalorraquidiano , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/psicologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Proteínas tau/líquido cefalorraquidiano
20.
J Biophotonics ; 14(4): e202000379, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33332747

RESUMO

Cortical spreading depression (CSD) has been observed during the early phase of subarachnoid hemorrhage (SAH). However, the effect of CSD on the cerebral blood flow (CBF) and cerebral oxyhemoglobin (CHbO) during the early phase of SAH has not yet been assessed directly. We, therefore, used laser speckle imaging and optical intrinsic sinal imaging to record CBF and CHbO during CSD and cerebral cortex perfusion (CCP) at 24 hours after CSD in a mouse model of SAH. SAH was induced by blood injection into the prechiasmatic cistern. When CSD occurred, the change trend of CBF and CHbO in Sham group and SAH group was the same, but ischemia and hypoxia in SAH group was more significant. At 24 hours after SAH, the CCP of CSD group was lower than that of no CSD group, and the neurological function score of CSD group was lower. We conclude that induction of CSD further aggravates cerebral ischemia and worsens neurological dysfunction in the early stage of experimental SAH. Our study underscores the consequence of CSD in the development of early brain injury after SAH.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Depressão Alastrante da Atividade Elétrica Cortical , Hemorragia Subaracnóidea , Animais , Lesões Encefálicas/complicações , Lesões Encefálicas/diagnóstico por imagem , Circulação Cerebrovascular , Modelos Animais de Doenças , Camundongos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/diagnóstico por imagem
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