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Giant intracerebral aneurysms (GIA) comprise up to 5 % of all intracranial aneurysms. The indirect surgical strategy, which leaves the GIA untouched but reverses the blood flow by performing a bypass in combination with proximal parent artery occlusion is a useful method to achieve spontaneous aneurysm occlusion. The goal of this study was to assess the utility of computational fluid dynamics (CFD) in preoperative GIA treatment planning. We hypothesise that CFD simulations will predict treatment results. A fluid-structure interaction (FSI) CFD investigation was performed for the entire arterial brain circulation. The analyses were performed in three patient-specific CT angiogram models. The first served as the reference geometry with a C6 internal carotid artery (ICA) GIA, the second a proximal parent artery occlusion (PAO) and virtual bypass to the frontal M2 branch of the middle cerebral artery (MCA), and the third a proximal PAO in combination with a temporal M2 branch bypass. The volume of "old blood", flow residence time (FRT), dynamic viscosity and haemodynamic changes were also analysed. The "old blood" within the aneurysm in the bypass models reached 41 % after 20 cardiac cycles while in the reference model it was fully washed out. In Bypass 2 "old blood" was also observed in the main trunk of the MCA after 20 cardiac cycles. Extrapolation of the results yielded a duration of 4 years required to replace the "old blood" inside the aneurysm after bypass revascularization. In both bypass models a 7-fold increase in mean blood viscosity in the aneurysm region was noted. Bypass revascularization combined with proximal PAO favours thrombosis. Areas prone to thrombus formation, and subsequently the treatment outcomes, were accurately identified in the preoperative model. Virtual surgical operations can give a remarkable insight into haemodynamics that could support operative decision-making.
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OBJECTIVE: Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The dynamic balance between the production and elimination of reactive oxygen species (ROS) in patients with DCI is suspected be shifted to favor ROS formation. The authors assessed the relationship between F2-isoprostanes (F2-IsoPs), oxidative stress biomarkers, and glucose-6-phosphate dehydrogenase (G6PD), which are responsible for nicotinamide adenine dinucleotide phosphate (NADPH) production for glutathione system function, with post-aSAH DCI. METHODS: The authors assessed 45 aSAH patients for F2-IsoP and G6PD concentration using commercial ELISA on days 2, 4, and 6 after aSAH. The authors examined the correlation between plasma F2-IsoP and G6PD concentrations and clinical factors with DCI occurrence and aSAH outcome. RESULTS: Expectedly, the most important clinical predictors of DCI were Hunt and Hess grade and modified Fisher (mFisher) grade. Plasma F2-IsoP and G6PD concentrations were greater in aSAH patients than the control group (p < 0.01). F2-IsoP concentrations were greater and G6PD concentrations were lower in patients with DCI than those without (p < 0.01). Plasma F2-IsoP and G6PD concentrations on day 2 were correlated with DCI occurrence (p < 0.01). Plasma F2-IsoP concentrations on days 2 and 6 were correlated with outcome at 1 and 12 months (p < 0.01). CONCLUSIONS: Decreased G6PD indirectly informs the reduced antioxidant response, especially for the glutathione system. G6PD concentration was lower in patients with DCI than those without, which may explain the increased F2-IsoP concentrations. mFisher grade, plasma F2-IsoP concentration, and G6PD concentration on day 2 after aSAH, in combination, may serve as predictors of DCI. Further research is necessary to investigate the therapeutic utility of F2-IsoPs and antioxidants in clinical practice.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Humanos , Dinoprosta , Glucosefosfato Desidrogenase , Espécies Reativas de Oxigênio , Estudos Prospectivos , Infarto Cerebral/complicações , GlutationaRESUMO
Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma.
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Lesões Encefálicas Traumáticas , Pressão Intracraniana , Encéfalo , Lesões Encefálicas Traumáticas/terapia , Escala de Resultado de Glasgow , Humanos , OxigênioRESUMO
Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer's exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35-105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9-45.08 ng/ml) [p = 0.03]. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/µl, 0.20-0.73 signal-intensity/µl, non-DCI: 0.28 signal-intensity/µl, 0.22-0.54 signal-intensity/µl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.
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Infarto Cerebral/líquido cefalorraquidiano , Infarto Cerebral/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/líquido cefalorraquidiano , Hemorragia Subaracnóidea/complicações , Idoso , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major cause of mortality and morbidity. The pathophysiology of DCI after aSAH is thought to involve toxic mediators released from lysis of red blood cells within the subarachnoid space, including free haemoglobin and haem. Haptoglobin and hemopexin are endogenously produced acute phase proteins that are involved in the clearance of these toxic mediators. The aim of this review is to investigate the pathophysiological mechanisms involved in DCI and the role of both endogenous as well as exogenously administered haptoglobin and hemopexin in the prevention of DCI.
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Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Haptoglobinas/uso terapêutico , Hemopexina/uso terapêutico , Hemorragia Subaracnóidea/complicações , HumanosRESUMO
INTRODUCTION: Seizure-related protein 6 (Sez6) contributes to chronic pain development as sez6 knockout mice show attenuated pain behaviours after peripheral nerve injury, compared with control mice. The type I transmembrane isoform of Sez6 is cleaved by the ß-amyloid precursor protein cleavage enzyme 1 (BACE1), resulting in Sez6 extracellular domain shedding from the neuron surface. OBJECTIVES: To determine whether this BACE1-shed form of Sez6 can be detected in the cerebrospinal fluid (CSF) and whether Sez6 levels in the CSF are altered in neuropathic pain or chronic inflammatory pain (IP). METHODS: We analysed the CSF samples collected during surgery from patients with chronic neuropathic pain (n = 8) or IP (n = 33), comparing them to the CSF samples from patients with suspected subarachnoid haemorrhage that was subsequently excluded (nonsurgical group, n = 5). Western blots were used to determine the relative Sez6 levels in the CSF from the different patient and nonsurgical comparison groups. RESULTS: The results show that BACE1-shed Sez6 can be readily detected in the CSF by Western blot and that the levels of Sez6 are significantly higher in the IP group than in the nonsurgical comparison group. CONCLUSION: The association between elevated Sez6 levels in the CSF and IP is further evidence for persistent alterations in central nervous system activity in chronic IP conditions.
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We report a case of a right-handed Caucasian woman who developed mirror writing following a non-aneurysmal, non-traumatic subarachnoid haemorrhage. The patient was unaware of having this phenomenon, and it was detected by clinical staff when the patient was writing a card to a family member. Serial imaging has ruled out a stroke as well as an underlying vascular abnormality. This phenomenon resolved after two months. Whilst there is a body of literature surrounding mirror writing, to our knowledge, this is the first description of mirror writing in the setting of a perimesencephalic subarachnoid haemorrhage.
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Lateralidade Funcional , Hemorragia Subaracnóidea/complicações , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Pilocytic astrocytomas (PA) are slow-growing low-grade gliomas, commonly diagnosed as cerebellar tumors among the pediatric and adolescent population. Characteristic neuroradiologic findings in PA include a cystic mass with enhancing solid nodule. While uncommon radiologic features of PA, including non-enhancing cystic tumors, have been previously described, we present a unique case of a patient with a non-enhancing solid cerebellar PA. The main clinical, radiologic, and pathologic findings are discussed and the relevant literature reviewed. To our knowledge, this is the first reported patient with these radiologic features of PA, highlighting the need for awareness of uncommon presentations when discussing differential diagnosis and pre-operative planning for cerebellar tumors in the relevant age group.
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Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Adolescente , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodosRESUMO
OBJECTIVEDelayed ischemic neurological deficit (DIND) is a leading cause of mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Arginine vasopressin (AVP) is a hormone released by the posterior pituitary. It is known to cause cerebral vasoconstriction and has been implicated in hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Direct measurement of AVP is limited by its short half-life. Copeptin, a cleavage product of the AVP precursor protein, was therefore used as a surrogate marker for AVP. This study aimed to investigate the temporal relationship between changes in copeptin concentrations and episodes of DIND and hyponatremia.METHODSCopeptin concentrations in cerebrospinal fluid were quantified using enzyme-linked immunosorbent assay in 19 patients: 10 patients with DIND, 6 patients without DIND (no-DIND), and 3 controls.RESULTSCopeptin concentrations were higher in DIND and no-DIND patients than in controls. In hyponatremic DIND patients, copeptin concentrations were higher compared with hyponatremic no-DIND patients. DIND was associated with a combination of decreasing sodium levels and increasing copeptin concentrations.CONCLUSIONSIncreased AVP may be the unifying factor explaining the co-occurrence of hyponatremia and DIND. Future studies are indicated to investigate this relationship and the therapeutic utility of AVP antagonists in the clinical setting.
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In 1995 a 16-year old girl was diagnosed with a large left thalamic AVM that was considered unsuitable for microsurgical resection and was treated with radiotherapy twice, which led to angiographic cure. She re-presented 19 years after initial treatment with a symptomatic acute thalamic haemorrhage. Her digital subtraction angiography was negative for arterio-venous shunting. MRI/MRA showed cystic change with adjacent contrast enhancement in the region of the previously irradiated arteriovenous malformation. The patient underwent an interhemispheric transcallosal resection of the left thalamic haemorrhagic lesion via a contralateral craniotomy. Intra-operatively there was a cystic cavity filled with blood products in association with thrombosed, calcified vessels as well as actively filling vessels. Histologically there were aggregated abnormal blood vessels with a dilated lumen and surrounded by brain parenchyma. Some of the vessel walls were thickened with fibrosis and some were arterialised with presence of elastin fibres. Potential mechanisms for the delayed haemorrhage are discussed.
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Hemorragia Cerebral/cirurgia , Malformações Arteriovenosas Intracranianas/radioterapia , Tálamo/irrigação sanguínea , Adolescente , Adulto , Angiografia Digital , Angiografia Cerebral , Hemorragia Cerebral/etiologia , Progressão da Doença , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Procedimentos Neurocirúrgicos , Radiocirurgia , Tálamo/cirurgia , Fatores de TempoRESUMO
OBJECTIVE MicroRNAs (miRNAs) regulate gene expression and therefore play important roles in many physiological and pathological processes. The aim of this pilot study was to determine the feasibility of extraction and subsequent profiling of miRNA from CSF samples in a pilot population of aneurysmal subarachnoid hemorrhage patients and establish if there is a distinct CSF miRNA signature between patients who develop cerebral vasospasm and those who do not. METHODS CSF samples were taken at various time points during the clinical management of a subset of SAH patients (SAH patient samples without vasospasm, n = 10; SAH patient samples with vasospasm, n = 10). CSF obtained from 4 patients without SAH was also included in the analysis. The miRNA was subsequently isolated and purified and then analyzed on an nCounter instrument using the Human V2 and V3 miRNA assay kits. The data were imported into the nSolver software package for differential miRNA expression analysis. RESULTS From a total of 800 miRNAs that could be detected with each version of the miRNA assay kit, a total of 691 miRNAs were communal to both kits. There were 36 individual miRNAs that were differentially expressed (p < 0.01) based on group analyses, with a number of miRNAs showing significant changes in more than one group analysis. The changes largely reflected differences between non-SAH and SAH groups. These included miR-204-5p, miR-223-3p, miR-337-5p, miR-451a, miR-489, miR-508-3p, miR-514-3p, miR-516-5p, miR-548 m, miR-599, miR-937, miR-1224-3p, and miR-1301. However, a number of miRNAs did exclusively differ between the vasospasm and nonvasospasm SAH groups including miR-27a-3p, miR-516a-5p, miR-566, and miR-1197. CONCLUSIONS The findings indicate that temporal miRNA profiling can detect differences between CSF from aneurysmal SAH and non-SAH patients. Moreover, the miRNA profile of CSF samples from patients who develop cerebral vasopasm may be distinguishable from those who do not. These results provide a foundation for future research at identifying novel CSF biomarkers that might predispose to the development of cerebral vasospasm after SAH and therefore influence subsequent clinical management.
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MicroRNAs/líquido cefalorraquidiano , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Hemorragia Subaracnóidea/terapia , Vasoespasmo Intracraniano/líquido cefalorraquidianoRESUMO
We report the acute formation of a cervical cord syrinx after aneurysmal subarachnoid haemorrhage, followed by spontaneous resolution. To our knowledge, not previously described in the literature, this case provides further insights into the pathophysiology of syrinx formation, and is discussed with reference to prevailing theories.
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Encéfalo/diagnóstico por imagem , Medula Cervical/diagnóstico por imagem , Hemorragia Subaracnóidea/complicações , Siringomielia/etiologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Hemorragia Subaracnóidea/diagnóstico por imagem , Siringomielia/diagnóstico por imagem , Tomografia Computadorizada por Raios XAssuntos
Neoplasias Encefálicas/patologia , Cistos do Sistema Nervoso Central/patologia , Epilepsia/etiologia , Epilepsia/patologia , Neurilemoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Cistos do Sistema Nervoso Central/complicações , Cistos do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurilemoma/complicações , Neurilemoma/diagnóstico , Tomografia Computadorizada por Raios XAssuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/metabolismo , Encéfalo/metabolismo , Hipertensão Intracraniana/etiologia , Ácido Láctico/metabolismo , Adolescente , Adulto , Idoso , Área Sob a Curva , Austrália , Biomarcadores/metabolismo , Lesões Encefálicas/fisiopatologia , Dermatite de Contato , Feminino , Humanos , Escala de Gravidade do Ferimento , Hipertensão Intracraniana/metabolismo , Masculino , Microdiálise/métodos , Pessoa de Meia-Idade , Razão de Chances , Seleção de Pacientes , Valor Preditivo dos Testes , Projetos de Pesquisa , Fatores de TempoRESUMO
Oxidative stress plays a significant role in secondary damage after severe traumatic brain injury (TBI); and melatonin exhibits both direct and indirect antioxidant effects. Melatonin deficiency is deleterious in TBI animal models, and its administration confers neuroprotection, reducing cerebral oedema, and improving neurobehavioural outcome. This study aimed to measure the endogenous cerebrospinal fluid (CSF) and serum melatonin levels post-TBI in humans and to identify relationships with markers of oxidative stress via 8-isoprostaglandin-F2alpha (isoprostane), brain metabolism and neurologic outcome. Cerebrospinal fluid and serum samples of 39 TBI patients were assessed for melatonin, isoprostane, and various metabolites. Cerebrospinal fluid but not serum melatonin levels were markedly elevated (7.28+/-0.92 versus 1.47+/-0.35 pg/mL, P<0.0005). Isoprostane levels also increased in both CSF (127.62+/-16.85 versus 18.28+/-4.88 pg/mL, P<0.0005) and serum (562.46+/-50.78 versus 126.15+/-40.08 pg/mL (P<0.0005). A strong correlation between CSF melatonin and CSF isoprostane on day 1 after injury (r=0.563, P=0.002) suggests that melatonin production increases in conjunction with lipid peroxidation in TBI. Relationships between CSF melatonin and pyruvate (r=0.369, P=0.049) and glutamate (r=0.373, P=0.046) indicate that melatonin production increases with metabolic disarray. In conclusion, endogenous CSF melatonin levels increase after TBI, whereas serum levels do not. This elevation is likely to represent a response to oxidative stress and metabolic disarray, although further studies are required to elucidate these relationships.
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Lesões Encefálicas/líquido cefalorraquidiano , Encéfalo/metabolismo , Melatonina/líquido cefalorraquidiano , Estresse Oxidativo/fisiologia , Adulto , Idoso , Lesões Encefálicas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Isoprostanos/líquido cefalorraquidiano , Masculino , Melatonina/sangue , Microdiálise , Pessoa de Meia-IdadeAssuntos
Empiema Subdural/microbiologia , Infecções por Escherichia coli/complicações , Pneumocefalia/microbiologia , Idoso de 80 Anos ou mais , Bacteriúria/complicações , Encéfalo/diagnóstico por imagem , Empiema Subdural/cirurgia , Escherichia coli/isolamento & purificação , Evolução Fatal , Hematoma Subdural/cirurgia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Activin A is a member of the transforming growth factor-beta superfamily and has been demonstrated to be elevated during inflammation and to have neuroprotective properties following neural insults. In this study, we examined whether traumatic brain injury (TBI) induced a response in activin A or in the concentrations of its binding protein, follistatin. Thirty-nine patients with severe TBI had daily, matched cerebrospinal fluid (CSF) and serum samples collected post-TBI and these were assayed for activin A and follistatin using specific immunoassays. Concentrations of both molecules were assessed relative to a variety of clinical parameters, such as the Glasgow Coma Score, computer tomography classification of TBI, measurement of injury markers, cell metabolism and membrane breakdown products. In about half of the patients, there was a notable increase in CSF activin A concentrations in the first few days post-TBI. There were only minor perturbations in either serum activin or in either CSF or serum follistatin concentrations. The CSF activin A response was not related to any of the common TBI indices, but was strongly correlated with two common markers of brain damage, neuronal specific enolase and S100-beta. Further, activin A levels were also associated with indices of metabolism, such as lactate and pyruvate, excitotoxicity (glutamate) and membrane lipid breakdown products such as glycerol. In one of the two patients who developed a CSF infection, activin A concentrations in CSF became markedly elevated. Thus, some TBI patients have an early release of activin A into the CSF that may result from activation of inflammatory and/or neuroprotective pathways.
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Ativinas/sangue , Ativinas/líquido cefalorraquidiano , Lesões Encefálicas/sangue , Lesões Encefálicas/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Lesões Encefálicas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Folistatina/sangue , Folistatina/líquido cefalorraquidiano , Ácido Glutâmico/sangue , Ácido Glutâmico/líquido cefalorraquidiano , Glicerol/sangue , Glicerol/líquido cefalorraquidiano , Humanos , Ácido Láctico/sangue , Ácido Láctico/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/líquido cefalorraquidiano , Fosfopiruvato Hidratase/sangue , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Ácido Pirúvico/sangue , Ácido Pirúvico/líquido cefalorraquidiano , Radiografia , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/sangue , Proteínas S100/líquido cefalorraquidiano , Índices de Gravidade do TraumaRESUMO
BACKGROUND: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and 'volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy. METHODS: A review of the literature was performed to examine the evidence base behind each intervention. RESULTS: There is no class I evidence to support the routine use of any of the therapies examined. CONCLUSION: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful.