RESUMO
Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.
Assuntos
Edema Encefálico , AVC Isquêmico , Humanos , Camundongos , Animais , Monócitos/metabolismo , Edema Encefálico/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/metabolismo , Infarto da Artéria Cerebral Média/metabolismoRESUMO
PURPOSE: To compare the outcomes of conducting left and right hemisphere surgical revascularization on the same day versus different days for bilateral pediatric moyamoya arteriopathy patients. METHODS: We retrospectively analyzed mortality, stroke, and transient neurologic event (TNE) rates in North American bilateral pediatric moyamoya arteriopathy patients who underwent bilateral cerebral revascularization. RESULTS: A total of 38 pediatric (≤ 18 years old) patients at our institution underwent bilateral cerebral revascularization for moyamoya arteriopathy. Of these patients, 24 (63.2%) had both operations on the same day and 14 (36.8%) had the two operations on different days. The average length of stay for patients who underwent same-day bilateral revascularization was 6.9 ± 2.0 days and the average length of stay for each operation for patients who underwent staged bilateral revascularization was 4.5 ± 1.4 days, p = 0.001. While there were 7 (14.6%) postoperative strokes in patients who had both hemispheres revascularized on the same day, 0 (0%) strokes occurred in hemispheres after they had been operated on in the staged cohort, p = 0.042. Additionally, the postoperative stroke-free survival time in the ipsilateral hemisphere and TNE-free survival time were significantly longer in patients in the staged revascularization cohort. CONCLUSION: Same-day bilateral revascularization was associated with longer length of stay per operation, higher rate of ipsilateral stroke, and shorter postoperative TNE-free and stroke-free survival time in the revascularized hemisphere.
Assuntos
Revascularização Cerebral , Doença de Moyamoya , Acidente Vascular Cerebral , Humanos , Criança , Adolescente , Estudos Retrospectivos , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Procedimentos Cirúrgicos Vasculares , Resultado do TratamentoRESUMO
OBJECTIVE: The safety and efficacy of anticoagulation in managing superior sagittal sinus (SSS) thrombosis remains unclear. The present study investigated the relationship between anticoagulation and cerebrovascular complications in parasagittal/parafalcine meningioma patients presenting with post-surgical SSS thrombosis. METHODS: We analyzed 266 patients treated at a single institution between 2005 and 2020. Bivariate analysis was conducted using the Mann-Whitney U test and Fisher's exact test. Multivariate analysis was conducted using a logistic regression model. Blood thinning medications investigated included aspirin, warfarin, heparin, apixaban, rivaroxaban, and other novel oral anticoagulants (NOACs). A symptomatic SSS thrombosis was defined as a radiographically apparent thrombosis with new headaches, seizures, altered sensorium, or neurological deficits. RESULTS: Our patient cohort was majority female (67.3%) with a mean age ([Formula: see text] SD) of 58.82 [Formula: see text] 13.04 years. A total of 15 (5.6%) patients developed postoperative SSS thrombosis and 5 (1.9%) were symptomatic; 2 (0.8%) symptomatic patients received anticoagulation. None of these 15 patients developed cerebrovascular complications following observation or anticoagulative treatment of asymptomatic SSS thrombosis. While incidence of any other postoperative complications was significantly associated with SSS thrombosis in bivariate analysis (p = 0.015), this association was no longer observed in multivariate analysis (OR = 2.15, p = 0.16) when controlling for patient age, sex, and anatomical location of the tumor along the SSS. CONCLUSIONS: Our single-institution study examining the incidence of SSS thrombosis and associated risk factors highlights the need for further research efforts better prognosticate this adverse outcome. Conservative management may represent a viable treatment strategy for patients with SSS thrombosis.
Assuntos
Anticoagulantes , Craniotomia , Neoplasias Meníngeas , Meningioma , Trombose do Seio Sagital , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Craniotomia/efeitos adversos , Feminino , Humanos , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Trombose do Seio Sagital/tratamento farmacológico , Trombose do Seio Sagital/etiologiaRESUMO
Concordance between the Unruptured Intracranial Aneurysm Treatment Score (UIATS), Earlier Subarachnoid Hemorrhage, Location, Age, Population, Size, Shape (ELAPSS) score, and Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, Site (PHASES) score with real-world management decisions in unruptured intracranial aneurysms (UIAs) remains unclear, especially in current practice. This study aimed to investigate this concordance, while developing an optimal model predictive of recent decision practices at a quaternary referral center. A prospective database of patients presenting with UIAs to our institution from January 1 to December 31, 2018, was used. Concordance between the scores and real-world management decisions on every UIA was assessed. Complications and length of stay (LOS) were compared between aneurysms in the UIATS-recommended treatment and observation groups. A subgroup analysis of concordance was also conducted among junior and senior surgeons. An optimal logistic regression model predictive of real-world decisions was also derived. The cohort consisted of 198 patients with 271 UIAs, of which 42% were treated. The UIATS demonstrated good concordance with an AUC of 0.765. Of the aneurysms in the UIATS-recommended "observation" group, 22% were discordantly treated. The ELAPSS score demonstrated good discrimination (AUC = 0.793), unlike the PHASES score (AUC = 0.579). Endovascular treatment rates, complications, and LOS were similar between aneurysms in the UIATS-recommended treatment and observation groups. Similar concordance was obtained among junior and senior surgeons. The optimal predictive model consisted of several significantly associated variables and had an AUC of 0.942. Cerebrovascular specialists may be treating aneurysms slightly more than these scores would recommend, independently of years in practice. Wide variation still exists in management practices of UIAs.
Assuntos
Gerenciamento Clínico , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Centros de Atenção Terciária , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/cirurgia , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta/tendências , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/cirurgia , Centros de Atenção Terciária/tendênciasRESUMO
The contribution of specific immune cell populations to the post-hemorrhagic inflammatory response in aneurysmal subarachnoid hemorrhage (aSAH) and correlations with clinical outcomes, such as vasospasm and functional status, remains unclear. We aimed to compare the predictive value of leukocyte ratios that include monocytes as compared to the neutrophil-to-lymphocyte ratio (NLR) in aSAH. A prospectively accrued database of consecutive patients presenting to our institution with aSAH between January 2013 and December 2018 was used. Patients with signs and symptoms of infection (day 1-3) were excluded. Admission values of the NLR, monocyte-neutrophil-to-lymphocyte ratio (M-NLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Associations with functional status, the primary outcome, and vasospasm were evaluated using univariable and multivariable logistic regression analyses. In the cohort of 234 patients with aSAH, the M-NLR and LMR, but not the NLR, were significantly associated with poor functional status (modified Rankin scale > 2) at 12-18 months following discharge (p = 0.001, p = 0.023, p = 0.161, respectively). The area under the curve for predicting poor functional status was significantly lower for the NLR (0.543) compared with the M-NLR (0.603, p = 0.024) and LMR (0.608, p = 0.040). The M-NLR (OR = 1.01 [1.01-1.02]) and LMR (OR = 0.88 [0.78-0.99]) were independently associated with poor functional status while controlling for age, hypertension, Fisher grade, and baseline clinical status. The LMR was significantly associated with vasospasm (OR = 0.84 [0.70-0.99]) while adjusting for age, hypertension, Fisher grade, aneurysm size, and current smoking. Inflammatory indices that incorporate monocytes (e.g., M-NLR and LMR), but not those that include only neutrophils, predict outcomes after aSAH.
Assuntos
Monócitos , Hemorragia Subaracnóidea , Estudos de Coortes , Humanos , Linfócitos , Neutrófilos , Prognóstico , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicaçõesRESUMO
The predictive values of current risk stratification scales such as the Unruptured Intracranial Aneurysm Treatment Score (UIATS) and the PHASES score are debatable. We evaluated these scores using a cohort of ruptured intracranial aneurysms to simulate their management recommendations had the exact same patients presented prior to rupture. A prospectively maintained database of ruptured saccular aneurysm patients presenting to our institution was used. The PHASES score was calculated for 992 consecutive patients presenting between January 2002 and December 2018, and the UIATS was calculated for 266 consecutive patients presenting between January 2013 and December 2018. A shorter period was selected for the UIATS cohort given the larger number of variables required for calculation. Clinical outcomes were compared between UIATS-recommended "observation" aneurysms and all other aneurysms. Out of 992 ruptured aneurysms, 54% had a low PHASES score (≤5). Out of the 266 ruptured aneurysms, UIATS recommendations were as follows: 68 (26%) "observation," 97 (36%) "treatment," and 101 (38%) "non-definitive." The UIATS conservative group of patients developed more SAH-related complications (78% vs. 65%, p=0.043), had a higher rate of non-home discharge (74% vs. 46%, p<0.001), and had a greater incidence of poor functional status (modified Rankin scale >2) after 12-18 months (68% vs. 51%, p=0.014). Current predictive scoring systems for unruptured aneurysms may underestimate future rupture risk and lead to more conservative management strategies in some patients. Patients that would have been recommended for conservative therapy were more likely to have a worse outcome after rupture.
Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Aneurisma Roto/diagnóstico , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Estudos de Coortes , Tratamento Conservador , Humanos , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R2eD arteriovenous malformation (acronym: R2eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.
Assuntos
Bases de Dados Factuais , Malformações Arteriovenosas Intracranianas , Hemorragias Intracranianas , Modelos Cardiovasculares , Adolescente , Adulto , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/fisiopatologia , Malformações Arteriovenosas Intracranianas/terapia , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Hemorragias Intracranianas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The Golden Ratio (Phi, or Φâ=â1.618 ) is a potentially unifying quantity of structure and function in nature, as best observed in phyllotactic patterns in plants. For centuries, Φ has been identified in human anatomy, and in recent decades, Φ has been identified in human physiology as well. The anatomy and evolution of the human skull have been the focus of intense study. Evolving over millenia, the human skull embodies an elegant harmonization of structure and function. The authors explored the dimensions of the neurocranium by focusing on the midline calvarial perimeter between the nasion and inion (nasioiniac arc) and its partition by bregma into 2 sub-arcs. The authors studied 100 human skulls and 70 skulls of 6 other mammalian species and calculated 2 ratios: 1) the nasioiniac arc divided by the parieto-occipital arc (between bregma and inion), and 2) the parieto-occipital arc divided by the frontal arc (between nasion and bregma). The authors report that in humans these 2 ratios coincide (1.64â±â0.04 and 1.57â±â0.10) and approximate Φ. In the other 6 mammalian species, these 2 ratios were not only different, but also unique to each species. The difference between the ratios showed a trend toward convergence on Φ correlating with species complexity. The partition of the nasioiniac arc by bregma into 2 unequal arcs is a situation analogous to that of the geometrical division of a line into Φ. The authors hypothesize that the Golden Ratio (Φ) principle, documented in other biological systems, may be present in the architecture and evolution of the human skull.
Assuntos
Crânio/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Animais , Feminino , Humanos , Masculino , Mamíferos , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Conclusions reached in existing literature about risk of arteriovenous malformation (AVM) hemorrhage during pregnancy are controversial. This study compares the risk of hemorrhage in pregnant and nonpregnant female patients with AVM in a North American cohort. METHODS: We retrospectively reviewed female patients with AVM evaluated from 1990 to 2015. Exposure period for pregnancy and puerperium was calculated as 40 and 6 weeks, respectively, for each full-term pregnancy and 6 weeks for each abortion. Hemorrhage events and patient-years were calculated during an exposure period (pregnancy and puerperium), and a nonexposure period defined as either the interval from birth until AVM obliteration or until last follow-up after subtracting exposure period. Poisson rate ratio test was used to compare rate of hemorrhage between exposure and nonexposure periods. RESULTS: For 270 female patients with AVM, mean age was 35.0±19.6 years, and race distribution was white (n=165, 61.1%), black (n=59, 21.9%), Hispanic (n=9, 3.3%), Asian (n=6, 2.2%), and other (n=31, 11.5%). From 191 total pregnancies occurring before AVM obliteration, there were 175 (91.6%) term deliveries and 16 (8.4%) abortions. Overall annual hemorrhage rate for 149 total hemorrhages during an average of 11 097 patient-years was 1.34%. There were 140 hemorrhages in nonexposed women and 9 hemorrhages in pregnant women, translating to an annual hemorrhage rate of 1.3% in nonpregnant women versus 5.7% in pregnant women (P<0.001). Identical analysis for reproductive age patients (15-50) demonstrated a rate of 1.3% versus 7.0% (P<0.001). CONCLUSIONS: Our results conflict with those from a recent study describing no increased rate of rupture during pregnancy. This difference may reflect unique population attributes influencing brain AVM hemorrhage during pregnancy.
Assuntos
Aneurisma Roto/epidemiologia , Fístula Arteriovenosa/epidemiologia , Hemorragia Cerebral/epidemiologia , Malformações Arteriovenosas Intracranianas/epidemiologia , Complicações Cardiovasculares na Gravidez/epidemiologia , Adolescente , Adulto , Aneurisma Roto/complicações , Fístula Arteriovenosa/complicações , Hemorragia Cerebral/etiologia , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/etiologia , Estudos Retrospectivos , Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to determine the duration, intensity, location, and usual treatment of pain throughout hospitalization following subarachnoid hemorrhage. BACKGROUND: Headache following subarachnoid hemorrhage can be sudden and severe. Little is known about the longitudinal course of headache or its analgesic therapy following the initial diagnosis of subarachnoid hemorrhage. METHODS: A prospectively maintained database of 564 patients diagnosed with cerebral aneurysms collected from 10/2009 to 2/2013 was searched for conscious patients with subarachnoid hemorrhage. Available electronic records were queried for pain scores (0-10/10), location, and analgesic consumption. RESULTS: Forty-six adults with subarachnoid hemorrhage met eligibility criteria for inclusion. Mean [CI 95] daily pain was 3.8 [3.2, 4.4] and maximal daily pain was 5.8 [5.1, 6.6]. Eighty-nine percent of patients reported severe pain of 7-10/10, and 63% of patients reported 10/10 pain at some point during hospitalization. While mean [CI 95] pain declined over the course of hospital stay at a rate of 0.06 [0.04, 0.07] units/day (P < .001), mean [CI 95] maximal daily pain changed at a rate of -0.03 [-0.06, 0.01] units/day, which is not significantly different than zero (P = .15). Pain was located primarily in the head in 76% of subjects but pain in the back, neck, limbs, and eyes was also reported. All patients received oral acetaminophen with increasing daily doses. All but three patients, received opioids, most commonly intravenous fentanyl and oral oxycodone. The mean [95 CI] intravenous morphine equivalent dose of opioids consumed was 15.7 [10.3, 21.1] mg/day and changed at a rate of -0.11 [-0.37, 0.15] mg/day which is not significantly different than zero (P = .40). CONCLUSION: Despite steady consumption of analgesics, the pain reported by conscious patients while recovering from subarachnoid hemorrhage in the hospital is often severe and persists throughout hospitalization.
Assuntos
Analgésicos/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Hemorragia Subaracnóidea/complicações , Adulto , Estudos de Coortes , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Análise de Regressão , Resultado do TratamentoRESUMO
BACKGROUND: The clinical relevance of chronic exposure to selective serotonin reuptake inhibitors (SSRIs) to transfusion in surgical patients is unclear. METHODS: We conducted a prospective cohort study involving patients undergoing cardiac, vascular, spinal, and intracranial surgery at 2 academic medical centers. Medication use, demographics, comorbidities, and laboratory values were determined at baseline by patient interview and review of medical records. The primary outcome was transfusion of any hemostatic allogeneic blood product (i.e., fresh frozen plasma, platelets, and/or cryoprecipitate) through postoperative day 2. RESULTS: The study sample consisted of 767 patients; 364 patients (47.5%) underwent cardiac surgery and the remainder underwent noncardiac surgery. Eighty-eight patients (11.5%) used SSRIs preoperatively. Among cardiac patients, the absolute number of allogeneic transfusions was higher for SSRI users than nonusers (2 [0-6] vs 0 [0-2], median [25%-75%], respectively, P = 0.008), and a similar trend was observed for noncardiac surgery. After adjusting for covariates using ordinal logistic regression, preoperative SSRI use was associated with an approximately 2-fold (odds ratio, 2.2; 95% confidence interval, 1.2-3.98) increase in odds of exposure to allogeneic hemostatic blood products; similar results were observed using propensity score adjustment (odds ratio, 1.85; 95% confidence interval, 1.11-3.07). A significant interaction between SSRI use and surgery type, age, sex, or concurrent antiplatelet therapy was not found; however, heterogeneity in magnitude of effect could not be excluded. CONCLUSIONS: Preoperative use of SSRIs is associated with increased exposure to allogeneic hemostatic blood products in surgical patients at high risk for perioperative bleeding. Determining whether perioperative continuation or withdrawal of SSRIs produces a net clinical benefit requires randomized controlled trials.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Hemorragia Pós-Operatória/prevenção & controle , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Centros Médicos Acadêmicos , Idoso , Baltimore , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Hemorragia Pós-Operatória/etiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: This study aims to characterize the clinical features, treatment strategies, and annual hemorrhage incidence rate of pediatric patients with multiple arteriovenous malformations (MAVM). METHODS: The PubMed and EMBASE databases and the arteriovenous malformations (AVM) database at the Johns Hopkins Hospital were searched for reports of pediatric patients (under 21 years of age) with MAVM. Data related to demographics, clinical features, management, and treatment outcomes were analyzed using descriptive statistics. Twenty-four pediatric patients met the inclusion criteria. RESULTS: The annual hemorrhage incidence rate was 2.1%. The most common presenting features were neurological deficit (38%) and hemorrhage (21%). Treatment with embolization has become the most frequently used modality. In patients undergoing staged treatment of MAVM, hemorrhage of an untreated nidus (n = 1), visualization of a new nidus (n = 2), or disappearance of a draining vein (n = 1) occurred. CONCLUSION: The annual hemorrhage incidence rate for pediatric patients with MAVM approaches the upper range of previously reported hemorrhage rates for solitary AVM. A staged approach to treating MAVM requires close follow-up as changes to the remaining nidi may occur during the latency period. Limitations of this study include its small sample size and reporting bias.
Assuntos
Hemorragia/etiologia , Malformações Arteriovenosas Intracranianas/complicações , Adolescente , Criança , Pré-Escolar , Embolização Terapêutica , Seguimentos , Humanos , Lactente , Radiocirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Mutations in ATP13A2 (PARK9), encoding a lysosomal P-type ATPase, are associated with both Kufor-Rakeb syndrome (KRS) and neuronal ceroid lipofuscinosis (NCL). KRS has recently been classified as a rare genetic form of Parkinson's disease (PD), whereas NCL is a lysosomal storage disorder. Although the transport activity of ATP13A2 has not been defined, in vitro studies show that its loss compromises lysosomal function, which in turn is thought to cause neuronal degeneration. To understand the role of ATP13A2 dysfunction in disease, we disrupted its gene in mice. Atp13a2(-/-) and Atp13a2(+/+) mice were tested behaviorally to assess sensorimotor and cognitive function at multiple ages. In the brain, lipofuscin accumulation, α-synuclein aggregation and dopaminergic pathology were measured. Behaviorally, Atp13a2(-/-) mice displayed late-onset sensorimotor deficits. Accelerated deposition of autofluorescent storage material (lipofuscin) was observed in the cerebellum and in neurons of the hippocampus and the cortex of Atp13a2(-/-) mice. Immunoblot analysis showed increased insoluble α-synuclein in the hippocampus, but not in the cortex or cerebellum. There was no change in the number of dopaminergic neurons in the substantia nigra or in striatal dopamine levels in aged Atp13a2(-/-) mice. These results show that the loss of Atp13a2 causes sensorimotor impairments, α-synuclein accumulation as occurs in PD and related synucleinopathies, and accumulation of lipofuscin deposits characteristic of NCL, thus providing the first direct demonstration that null mutations in Atp13a2 can cause pathological features of both diseases in the same organism.
Assuntos
Adenosina Trifosfatases , Envelhecimento/metabolismo , Encéfalo/metabolismo , Retroalimentação Sensorial , Proteínas de Membrana , Lipofuscinoses Ceroides Neuronais/enzimologia , Transtornos Parkinsonianos/enzimologia , alfa-Sinucleína/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Animais , Comportamento Animal , Encéfalo/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Humanos , Camundongos , Camundongos Mutantes , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/patologia , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/patologia , ATPases Translocadoras de Prótons , alfa-Sinucleína/genéticaRESUMO
Aneurysms of the posterior circulation remain challenging lesions given their proximity to the brainstem and cranial nerves. Many of these aneurysms may best be approached through a retrosigmoid-suboccipital craniectomy with a far-lateral transcondylar extension. In this narrated video illustration, we present the case of a 37-year-old man with an incidentally discovered right-sided anterior inferior cerebellar artery (AICA) aneurysm. Diagnostic studies included CT angiography and cerebral angiography. A suboccipital craniectomy and far-lateral transcondylar extension were performed for microsurgical trapping and excision of the AICA aneurysm. The techniques of the retrosigmoid craniectomy, C-1 laminectomy, condylectomy and microsurgical trapping of the aneurysm are reviewed. The video can be found here: http://youtu.be/JiM3CXVwXnk.
Assuntos
Artérias Cerebrais/cirurgia , Aneurisma Intracraniano/cirurgia , Microcirurgia/métodos , Osso Occipital/cirurgia , Adulto , Cerebelo/patologia , Cerebelo/cirurgia , Angiografia Cerebral , Craniotomia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: There are uncertainties surrounding the optimal management of patients with brain swelling after an ischemic stroke. Guidelines are needed on how to manage this major complication, how to provide the best comprehensive neurological and medical care, and how to best inform families facing complex decisions on surgical intervention in deteriorating patients. This scientific statement addresses the early approach to the patient with a swollen ischemic stroke in a cerebral or cerebellar hemisphere. METHODS: The writing group used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. The panel reviewed the most relevant articles on adults through computerized searches of the medical literature using MEDLINE, EMBASE, and Web of Science through March 2013. The evidence is organized within the context of the American Heart Association framework and is classified according to the joint American Heart Association/American College of Cardiology Foundation and supplementary American Heart Association Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive American Heart Association internal peer review. RESULTS: Clinical criteria are available for hemispheric (involving the entire middle cerebral artery territory or more) and cerebellar (involving the posterior inferior cerebellar artery or superior cerebellar artery) swelling caused by ischemic infarction. Clinical signs that signify deterioration in swollen supratentorial hemispheric ischemic stroke include new or further impairment of consciousness, cerebral ptosis, and changes in pupillary size. In swollen cerebellar infarction, a decrease in level of consciousness occurs as a result of brainstem compression and therefore may include early loss of corneal reflexes and the development of miosis. Standardized definitions should be established to facilitate multicenter and population-based studies of incidence, prevalence, risk factors, and outcomes. Identification of patients at high risk for brain swelling should include clinical and neuroimaging data. If a full resuscitative status is warranted in a patient with a large territorial stroke, admission to a unit with neurological monitoring capabilities is needed. These patients are best admitted to intensive care or stroke units attended by skilled and experienced physicians such as neurointensivists or vascular neurologists. Complex medical care includes airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In swollen supratentorial hemispheric ischemic stroke, routine intracranial pressure monitoring or cerebrospinal fluid diversion is not indicated, but decompressive craniectomy with dural expansion should be considered in patients who continue to deteriorate neurologically. There is uncertainty about the efficacy of decompressive craniectomy in patients ≥60 years of age. In swollen cerebellar stroke, suboccipital craniectomy with dural expansion should be performed in patients who deteriorate neurologically. Ventriculostomy to relieve obstructive hydrocephalus after a cerebellar infarct should be accompanied by decompressive suboccipital craniectomy to avoid deterioration from upward cerebellar displacement. In swollen hemispheric supratentorial infarcts, outcome can be satisfactory, but one should anticipate that one third of patients will be severely disabled and fully dependent on care even after decompressive craniectomy. Surgery after a cerebellar infarct leads to acceptable functional outcome in most patients. CONCLUSIONS: Swollen cerebral and cerebellar infarcts are critical conditions that warrant immediate, specialized neurointensive care and often neurosurgical intervention. Decompressive craniectomy is a necessary option in many patients. Selected patients may benefit greatly from such an approach, and although disabled, they may be functionally independent.
Assuntos
American Heart Association , Edema Encefálico/terapia , Doenças Cerebelares/terapia , Infarto Cerebral/terapia , Cuidados Críticos/normas , Neurologia/normas , Procedimentos Neurocirúrgicos/normas , Adulto , Edema Encefálico/mortalidade , Edema Encefálico/cirurgia , Doenças Cerebelares/mortalidade , Doenças Cerebelares/cirurgia , Infarto Cerebral/mortalidade , Infarto Cerebral/cirurgia , Humanos , Estados UnidosRESUMO
Spinal vascular lesions are rare and may be classified as a) dural arteriovenous fistulas (AVFs), b) arteriovenous malformations, or c) perimedullary AVFs. In this narrated video illustration, we present the case of a 71-year-old woman who presented with progressive bilateral lower extremity weakness and urinary retention who was diagnosed with a thoracic spinal perimedullary arteriovenous fistula. The diagnostic studies included a thoracic MRI and spinal angiogram. A multilevel thoracic laminoplasty was performed for microsurgical obliteration of the AVF. The techniques of intraoperative angiography, thoracic laminoplasty and microsurgical obliteration and resection of the AVF are reviewed. The video can be found here: http://youtu.be/5vVp3oq5sLg.
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Fístula Arteriovenosa/cirurgia , Microcirurgia/métodos , Doenças Vasculares da Medula Espinal/cirurgia , Medula Espinal/cirurgia , Idoso , Angiografia , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: The Hunt and Hess grade and World Federation of Neurological Surgeons (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to improve the accuracy of mortality prediction compared with the aforementioned scales by creating the "SAH score." METHODS: The aSAH database at our institution was analyzed for factors affecting in-hospital mortality using multiple logistic regression analysis. Scores were weighted based on relative risk of mortality after stratification of each of these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4 (score = 1), 5-8 (score = 2), 9-13 (score = 3), and 14-15 (score = 4). Age was categorized into 4 subgroups: 18-49 (score = 1), 50-69 (score = 2), 70-79 (score = 3), and 80 years or more (score = 4). Medical comorbidities were subdivided into none (score = 1), 1 (score = 2), or 2 or more (score = 3). RESULTS: In total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%. Admission GCS, age, and medical comorbidities significantly affected mortality after multivariate analysis (P < .05). Summated scores ranged from 0 to 8 with escalating mortality at higher scores (0 = 2%, 1 = 6%, 2 = 8%, 3 = 15%, 4 = 30%, 5 = 58%, 6 = 79%, 7 = 87%, and 8 = 100%). Positive predictive value (PPV) for scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777, fair accuracy) and the Hunt and Hess grade (AUC .771, fair accuracy). CONCLUSIONS: The SAH score was found to be more accurate in predicting aSAH mortality compared with the Hunt and Hess grade and WFNS scale.
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Técnicas de Apoio para a Decisão , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Distribuição de Qui-Quadrado , Comorbidade , Feminino , Escala de Coma de Glasgow , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Decision-making for the management of ruptured deep-seated brain arteriovenous malformations (bAVMs) is controversial. This study aimed to shed light on the treatment outcomes of patients with ruptured deep-seated bAVMs. METHODS: Data on bAVM patients were retrieved from the authors' institutional database, spanning 1990-2021. The outcomes were annual hemorrhage risk (before and after intervention), number of follow-up hemorrhages, bAVM obliteration, poor modified Rankin Scale (mRS) score (i.e., mRS score > 2), worsened mRS score, and mortality. Multivariable Cox and logistic regression analyses were conducted to determine predictors of time-to-event and categorical outcomes, respectively. RESULTS: Of the 1066 patients in the database with brain bAVM, 177 patients harboring ruptured deep-seated bAVMs were included. The pretreatment annual hemorrhage risk was 8.24%, and the posttreatment risk was lowered to 1.65%. In multivariable Cox regression analysis, a prenidal aneurysm (HR 2.388, 95% CI 1.057-5.398; p = 0.036) was associated with a higher risk of follow-up hemorrhage, while definitive treatment (i.e., either surgery or radiosurgery vs endovascular embolization or conservative management) (HR 0.267, 95% CI 0.118-0.602; p = 0.001) was associated with a lower risk of follow-up hemorrhage. In multivariable logistic regression analysis, Spetzler-Martin grades IV and V (OR 0.404, 95% CI 0.171-0.917; p = 0.033) and brainstem arteriovenous malformation (AVM) (OR 0.325, 95% CI 0.128-0.778; p = 0.014) were associated with lower odds of obliteration, while definitive treatment (OR 8.864, 95% CI 3.604-25.399; p = 0.008) was associated with higher obliteration odds. Controlling for baseline mRS score, cerebellar AVM (OR 0.286, 95% CI 0.098-0.731; p = 0.013) and definitive treatment (OR 0.361, 95% CI 0.160-0.807; p = 0.013) were associated with lower odds of a poor mRS score, and definitive treatment (OR 0.208, 95% CI 0.076-0.553; p = 0.001) was associated with lower odds of a worsened mRS score. Furthermore, smoking (OR 6.068, 95% CI 1.531-25.581; p = 0.01) and definitive treatment (OR 0.101, 95% CI 0.024-0.361; p = 0.007) were associated with higher and lower mortality odds, respectively. CONCLUSIONS: A definitive treatment strategy seems to be beneficial in achieving higher obliteration and lower hemorrhage rates while decreasing the odds of a poor mRS score, worsened mRS score, and mortality. In this category of patients, prenidal aneurysms warrant treatment, and smoking cessation should be encouraged.
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Malformações Arteriovenosas Intracranianas , Ketamina , Humanos , Encéfalo , Tronco Encefálico , Cerebelo , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/terapia , HemorragiaRESUMO
BACKGROUND AND OBJECTIVES: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes. METHODS: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ 2 , univariate, and multivariate logistic regression analyses were used to analyze risk factors. RESULTS: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus , Klebsiella , and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia. CONCLUSION: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections.
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Isquemia Encefálica , Infecção Hospitalar , Pneumonia , Hemorragia Subaracnóidea , Infecções Urinárias , Adulto , Humanos , Masculino , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/cirurgia , Isquemia Encefálica/etiologia , Infarto Cerebral/complicações , Fatores de Risco , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/complicações , Pneumonia/complicações , Infecções Urinárias/etiologia , Infecções Urinárias/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear. METHODS: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ2 and multivariate ordinal regression. RESULTS: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02). CONCLUSIONS: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed.