Homocysteine serum levels in patients with ruptured and unruptured intracranial aneurysms: a case-control study / Homocisteína sérica em pacientes com aneurismas rotos e não rotos: um estudo caso-controle

Abstract Background There is very few data regarding homocysteine's influence on the formation and rupture of intracranial aneurysms. Objective To compare homocysteine levels between patients with ruptured and unruptured intracranial aneurysms, and to evaluate possible influences of this molecule on vasospasm and functional outcomes. Methods This is a retrospective, case-control study. We evaluated homocysteinemia differences between patients with ruptured and unruptured aneurysms; and the association of homocysteine levels with vasospasm and functional outcomes. Logistic regressions were performed. Results A total of 348 participants were included: 114 (32.8%) with previous aneurysm rupture and 234 (67.2%) with unruptured aneurysms. Median homocysteine was 10.75μmol/L (IQR = 4.59) in patients with ruptured aneurysms and 11.5μmol/L (IQR = 5.84) in patients with unruptured aneurysms. No significant association was detected between homocysteine levels and rupture status (OR = 0.99, 95% CI = 0.96-1.04). Neither mild (>15μmol/L; OR = 1.25, 95% CI 0.32-4.12) nor moderate (>30μmol/L; OR = 1.0, 95% CI = 0.54-1.81) hyperhomocysteinemia demonstrated significant correlations with ruptured aneurysms. Neither univariate (OR = 0.86; 95% CI 0.71-1.0) nor multivariable age-adjusted (OR = 0.91; 95% CI = 0.75-1.05) models evidenced an association between homocysteine levels and vasospasm. Homocysteinemia did not influence excellent functional outcomes at 6 months (mRS≤1) (OR = 1.04; 95% CI = 0.94-1.16). Conclusion There were no differences regarding homocysteinemia between patients with ruptured and unruptured intracranial aneurysms. In patients with ruptured aneurysms, homocysteinemia was not associated with vasospasm or functional outcomes.

RESUMO Antecedentes Existem poucos dados sobre a influência da homocisteína na formação e rotura de aneurismas intracranianos (AI). Objetivo Comparar os níveis de homocisteína entre pacientes com AI rotos e não rotos e influências no vasoespasmo e resultados funcionais. Métodos Estudo caso-controle, que avaliou as diferenças de homocisteinemia entre pacientes com aneurismas rotos e não rotos, além da associação entre níveis de homocisteína, vasoespasmo e estado funcional. Regressões logísticas foram realizadas. Resultados Um total de 348 participantes foram incluídos: 114 (32,8%) com aneurismas rotos e 234 (67,2%) não rotos. A homocisteína mediana foi de 10,75μmol/L (IQR = 4,59) nos rotos e 11,5μmol/L (IQR = 5,84) nos não rotos. Não houve associação significativa entre os níveis de homocisteína e o status de ruptura (OR = 0,99, 95% CI = 0,96-1,04). Nem a hiperhomocisteinemia leve (>15μmol/L; OR = 1,25, 95% CI = 0,32-4,12) nem a moderada (>30μmol/L; OR = 1,0, 95% CI = 0,54-1,81) mostraram correlações significativas com aneurismas rotos. Modelos univariados (OR = 0,86; 95% CI = 0,71-1,0) e multivariados ajustados por idade (OR = 0,91; 95% CI = 0,75-1,05) não evidenciaram associação entre homocisteína e vasoespasmo. A homocisteinemia não influenciou resultados funcionais excelentes em seis meses (mRS ≤ 1) (OR = 1,04; 95% CI = 0,94-1,16). Conclusão Não houve diferenças em relação à homocisteinemia entre pacientes com aneurismas intracranianos rotos e não rotos. Em pacientes com aneurismas rotos, a homocisteinemia não foi associada ao vasoespasmo ou resultados funcionais.

Repercussions of the Emergency neurological life support on scientific literature: a bibliometric study / Repercussões do Emergency neurological life support na literatura científica: um estudo bibliométrico

Abstract Background In 2012, the Neurocritical Care Society launched a compilation of protocols regarding the core issues that should be addressed within the first hours of neurological emergencies - the Emergency neurological life support (ENLS). Objective We aim to evaluate this repercussion through a bibliometric analysis. Methods We searched Scopus on October 2022 for articles mentioning ENLS. The following variables were obtained: number of citations; number of citations per year; number of publications per year; year of publication; research type; research subtype; country of corresponding author and its income category and world region; journal of publication and its 5-year impact factor (IF); and section where ENLS appeared. Results After applying eligibility criteria, we retrieved 421 articles, published from 2012 to 2022. The mean number of citations per article was 17.46 (95% Confidence Interval (CI) = 8.20-26.72), while the mean number of citations per year per article was 4.05 (95% CI = 2.50-5.61). The mean destiny journal 5-year IF was 5.141 (95% CI = 4.189-6.093). The majority of articles were secondary research (57.48%; n= 242/421) of which most were narrative reviews (71.90%; n= 174/242). High-Income countries were the most prominent (80.05%; n= 337/421 articles). There were no papers from low-income countries. There were no trials or systematic reviews from middle-income countries. Conclusion Although still low, the number of publications mentioning ENLS is increasing. Articles were mainly published in journals of intensive care medicine, neurology, neurosurgery, and emergency medicine. Most articles were published by authors from high-income countries. The majority of papers were secondary research, with narrative review as the most frequent subtype.

Resumo Antecedentes Em 2012, a Neurocritical Care Society lançou uma compilação de protocolos sobre as questões centrais que devem ser abordadas nas primeiras horas de emergências neurológicas - Emergency neurological life support (ENLS). Objetivo Avaliar a repercussão do ENLS por meio de uma análise bibliométrica. Métodos A base de dados Scopus foi utilizada em outubro de 2022 para a busca por artigos mencionando o ENLS. As seguintes variáveis foram obtidas: número de citações; número de citações por ano; número de publicações por ano; ano de publicação; tipo de pesquisa; país do autor correspondente e sua categoria de renda; revista de publicação e seu fator de impacto de 5 anos (IF); e seção onde o ENLS apareceu. Resultados Os 421 artigos incluídos foram publicados de 2012 a 2022. A média de citações por artigo foi de 17.46 (intervalo de confiança (IC) 95% = 8.20-26.72), enquanto a de citações por ano por artigo foi de 4.05 (IC95% = 2.50-5.61). O IF médio por revista foi de 5.14 (IC95% = 4.19-6.09). A maioria dos artigos era de pesquisa secundária (57.48%; n= 242/421), dos quais a maioria eram revisões narrativas (71.90%; n= 174/242). Os países de alta renda foram os mais prolíficos (80.05%; n= 337/421 artigos). Não houve publicações de países de baixa ou média renda. Conclusão Embora ainda baixo, o número de publicações mencionando o ENLS vem aumentando recentemente. A maioria dos artigos foram publicados em revistas de medicina intensiva, neurologia, neurocirurgia e medicina de emergência. Artigos de pesquisa secundária foram os mais comuns, com revisões narrativas sendo o subtipo mais frequente.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and prognosis after aneurysmal subarachnoid hemorrhage: a cohort study / Razão neutrófilos-linfócitos e razão plaquetas-linfócitos e o prognóstico de hemorragia subaracnóidea aneurismática: um estudo de coorte

Abstract Background Subarachnoid hemorrhage (SAH) prognosis remains poor. Vasospasm mechanism might be associated with inflammation. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been studied as inflammation markers and prognostic predictors. Objective We aimed to investigate NLR and PLR in admission as predictors of angiographic vasospasm and functional outcome at 6 months. Methods This cohort study included consecutive aneurysmal SAH patients admitted to a tertiary center. Complete blood count was recorded at admission before treatment. White blood cell count, neutrophil count, lymphocyte count, platelet count, NLR, and PLR were collected as independent variables. Vasospasm occurrence-modified Rankin scale (mRS), Glasgow outcome scale (GOS), and Hunt-Hess score at admission and at 6 months were recorded as dependent variables. Multivariable logistic regression models were used to adjust for potential confounding and to assess the independent prognostic value of NLR and PLR at admission. Results A total of 74.1% of the patients were female, with mean age of 55.6 ± 12.4 years. At admission, the median Hunt-Hess score was 2 (interquartile range [IQR] 1), and the median mFisher was 3 (IQR 1). Microsurgical clipping was the treatment for 66.2% of the patients. Angiographic vasospasm incidence was 16.5%. At 6 months, the median GOS was 4 (IQR 0.75), and the median mRS was 3 (IQR 1.5). Twenty-one patients (15.1%) died. Neutrophil-to-lymphocyte ratio and PLR levels did not differ between favorable and unfavorable (mRS > 2 or GOS < 4) functional outcomes. No variables were significantly associated with angiographic vasospasm. Conclusion Admission NLR and PLR presented no value for prediction of functional outcome or angiographic vasospasm risk. Further research is needed in this field.

Resumo Antecedentes O prognóstico da hemorragia subaracnoidea (HSA) permanece ruim. Vasoespasmo pode estar associado à inflamação. Razões neutrófilo-linfócito (NLR) e plaqueta-linfócito (PLR) têm sido estudadas como marcadores de inflamação e prognóstico. Objetivo Investigar NLR e PLR na admissão como preditores de vasoespasmo angiográfico e desfecho aos 6 meses. Métodos Este estudo de coorte incluiu pacientes consecutivos com HSA aneurismática de um centro terciário. Contagem de leucócitos, neutrófilos, linfócitos e plaquetas, proporção de neutrófilos para linfócitos e de plaquetas para linfócitos foram coletados como variáveis independentes. Ocorrência de vasoespasmo, escala de Rankin modificada, escala de desfecho de Glasgow e o escore de Hunt-Hess na admissão e 6 meses após a mesma foram registradas como variáveis dependentes. Modelos de regressão logística multivariável foram usados para ajustar potenciais fatores de confusão e avaliar valor prognóstico independente de NLR e PLR. Resultados Um total de 74,1% pacientes eram do sexo feminino, com idade média de 55,6 ± 12,4 anos. Na admissão, a pontuação média de Hunt-Hess foi de 2 (IQR 1) e a mediana de mFisher foi de 3 (IQR 1). Clipagem microcirúrgica foi o tratamento escolhido para 66,2% dos pacientes. A incidência de vasoespasmo angiográfico foi de 16,5%. Aos 6 meses, a escala de desfecho de Glasgow mediana era 4 (IQR 0,75) e a escala de Rankin modificada mediana era 3 (IQR 1,5). Vinte e um pacientes (15,1%) morreram. Os níveis de NLR e PLR não diferiram entre resultados funcionais favoráveis e desfavoráveis (mRS > 2 ou GOS < 4). Nenhuma variável foi significativamente associada ao vasoespasmo angiográfico. Conclusão Razão neutrófilo-linfócito e a PLR não apresentaram valor preditivo de desfecho funcional ou risco de vasoespasmo angiográfico. Mais pesquisas são necessárias neste campo.

Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis

SUMMARY OBJECTIVE: The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage. METHODS: This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review. RESULTS: Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2). CONCLUSION: The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.

Role of temporary arterial occlusion in subarachnoid hemorrhage outcomes: a prospective cohort study

Purpose: Temporary arterial occlusion (TAO) is a widespread practice in the surgical treatment of intracranial aneurysms. This study aimed to investigate TAO's role during ruptured aneurysm clipping as an independent prognostic factor on short- and long-term outcomes. Methods: This prospective cohort included 180 patients with ruptured intracranial aneurysms and an indication of microsurgical treatment. Patients who died in the first 12 hours after admission were excluded. Results: TAO was associated with intraoperative rupture (IOR) (odds ratio ­ OR = 10.54; 95% confidence interval ­ 95%CI 4.72­23.55; p < 0.001) and surgical complications (OR = 2.14; 95%CI 1.11­4.07; p = 0.01). The group with TAO and IOR had no significant difference in clinical (p = 0.06) and surgical (p = 0.94) complications compared to the group that had TAO, but no IOR. Among the 111 patients followed six months after treatment, IOR, number of occlusions, and total time of occlusion were not associated with Glasgow Outcome Scale (GOS) in the follow-up (respectively, p = 0.18, p = 0.30, and p = 0.73). Among patients who underwent TAO, IOR was also not associated with GOS in the follow-up (p = 0.29). Conclusions: TAO was associated with IOR and surgical complications, being the latter independent of IOR occurrence. In long-term analysis, neither TAO nor IOR were associated with poor clinical outcomes.

The preoperative neutrophil-to-lymphocyte ratio predictive value for survival in patients with brain metastasis / O valor do índice neutrófilo-linfócito como preditor de sobrevida em pacientes com metástases cerebrais

Abstract Background The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) have been previously studied as predictors of survival in different malignancies. Objective The aim of this study was to evaluate the predictive value of these hematologic inflammatory biomarkers for patients with brain metastases (BM). Methods We reviewed a consecutive cohort of patients at Instituto do Cancer do Estado de São Paulo (ICESP-FMUSP) from 2011 to 2016 with ≥ 1 BM treated primarily by surgical resection. The primary outcome was 1-year survival. We optimized the NLR, MLR, PLR, and RDW cutoff values, preserving robustness and avoiding overestimation of effect size. Results A total of 200 patients (mean age 56.1 years; 55.0% female) met inclusion criteria. Gross-total resection was achieved in 89.0%. The median (quartiles) preoperative and postoperative KPS scores were 60 (50-80) and 80 (60-90), respectively. Preoperative NLR was significantly associated with survival (HR 2.66, 95% CI: 1.17-6.01, p = 0.019). A NLR cutoff value of 3.83 displayed the most significant survival curve split. Conclusions Preoperative NLR is an independent predictor of survival in newly diagnosed BM. We propose a cutoff value of 3.83 for preoperative NLR testing may be clinically useful as predictor of poor survival in this population. The wide accessibility of the NLR favors its inclusion in clinical decision-making processes for BM management.

Resumo Antecedentes Os neutrófilos para linfócitos (NLR), monócitos para linfócitos (MLR), proporção de plaquetas para linfócitos (PLR) e largura de distribuição de glóbulos vermelhos (RDW) foram previamente estudados como preditores de sobrevivência em diferentes malignidades. Objetivo O objetivo deste estudo foi avaliar o valor preditivo desses biomarcadores inflamatórios hematológicos para pacientes com metástases cerebrais (MB). Métodos Nós revisamos uma coorte consecutiva de pacientes no Instituto do Câncer do Estado de São Paulo (ICESP-FMUSP) de 2011 a 2016 com ≥ 1 MB tratados principalmente por ressecção cirúrgica. O desfecho primário foi a sobrevida em 1 ano. Otimizamos os valores de corte de NLR, MLR, PLR e RDW, preservando a robustez e evitando superestimação do tamanho do efeito. Resultados Um total de 200 pacientes (idade média de 56,1 anos; 55,0% mulheres) preencheram os critérios de inclusão. A ressecção grosseira total foi obtida em 89,0%. A mediana (quartis) dos escores KPS pré-operatório e pós-operatório foram 60 (50-80) e 80 (60-90), respectivamente. O NLR pré-operatório foi significativamente associado à sobrevida (HR 2,66, IC 95%: 1,17-6,01, p = 0,019). Um valor de corte de NLR de 3,83 exibiu a divisão da curva de sobrevivência mais significativa. Conclusões O NLR pré-operatório é um preditor independente de sobrevida em MBs recém-diagnosticados. Propomos que um valor de corte de 3,83 para o teste de NLR pré-operatório pode ser clinicamente útil como preditor de baixa sobrevida nesta população. A ampla acessibilidade do NLR favorece sua inclusão nos processos de tomada de decisão clínica para o gerenciamento de BM.

Analysis of serum cholesterol, statins and atherosclerotic plaque in ruptured and unruptured intracranial aneurysm / Análise de colesterol sérico, estatina e placa aterosclerótica em aneurisma intracraniano roto e não roto

Introduction Intracranial aneurysm (IA) is a major healthcare concern. The use of statin to reduce serum cholesterol has shown evidence to reduce cardiovascular risk in various diseases, but the impact on IA has not been described. This study aims to determine whether statin use, and serum cholesterol levels interfere with outcomes after IA event. Methods A cohort of patients with IA was analyzed. Patients social and demographics data were collected.Modified Rankin scale (mRS) score after 6months of follow-up was the endpoint. The data regarding statins use, presence or not of atherosclerotic plaque in radiological images and serum cholesterol of 35 patients were included in our study. Linear regression models were used to determine the influence of those 6 variables in the clinical outcome. Results The prevalence of atherosclerotic plaque, high cholesterol and use of statins was 34.3%, 48.5%, and 14.2%, respectively. Statins and serum cholesterol did not impact the overall outcome,measured by mRS after 6 months (p>0.05), but did show different tendencies when separated by IA rupture status. Serum cholesterol shows na important association with rupture of aneurysm (p»0.0382). High cholesterol and use of statins show a tendency for worse outcome with ruptured aneurysm, and the opposite is true for unruptured aneurysm. The presence of atherosclerotic plaques was not related with worse outcomes. Conclusions Multiple and opposite mechanisms might be involved in the pathophysiology of IA. Ruptured aneurysms are associated with higher levels of serum cholesterol. Serum cholesterol and statins use were not correlated with worse outcomes, but further studies are important to clarify these relationships.

Introdução Aneurisma intracranial (AI) é uma grande preocupação para a saúde. Evidências apontam que o uso de estatina para reduzir o colesterol sérico diminui o risco cardiovascular em diversas doenças, mas o impacto em AI ainda não foi descrito. Este estudo almeja determinar se o uso de estatina e o nível sérico de colesterol interferem no desfecho clínico após a ocorrência de AIs. Métodos Uma coorte de pacientes com AI foi analisada. Os dados sociodemográficos dos pacientes foram coletados. Ao final de 6 meses de acompanhamento, aplicou-se a escala modificada de Rankin (mRS). Os dados sobre uso de estatina, existência de placa aterosclerótica em imagens radiológicas, e colesterol sérico de 35 pacientes foram incluídos no estudo. Modelos de regressão linear foram usados para determinar a influência dessas 6 variáveis nos desfechos clínicos. Resultados A prevalência de placa aterosclerótica, colesterol elevado, e uso de estatina foram respectivamente 34,3%, 48,5% e 14,2%. Estatina e colesterol sérico não impactaram nos desfechos medidos pela mRS em 6 meses (p > 0,05), mas mostraram diferentes tendências quando separados pelo estado de ruptura do AI. Colesterol sérico apresenta uma importante associação com ruptura de aneurisma (p » 0,0382). Colesterol elevado e uso de estatinas representam uma tendência a piores desfechos para aneurismas rompidos, e o oposto é verdade para os não rompidos. A presença de placa aterosclerótica não está relacionada com piores resultados. Conclusões Mecanismos múltiplos e opostos podem estar envolvidos na patofisio logia do AI. Aneurismas rompidos estão associados com maiores níveis de colesterol sérico. Colesterol sérico e estatinas não foram correlacionados com piores desfechos, mas mais estudos são importantes para clarificar a relação entre esses fatores

Um cirurgião sob o olhar de Deus

Objetivo A síndrome de Terson (ST), também conhecida como hemorragia vítrea, é relatada em pacientes com hemorragia subaracnóide causada por um aneurisma rompido. Este estudo tem como objetivo avaliar a presença de hemorragia ocular nesses pacientes, buscando identificar aqueles que poderiam se beneficiar do tratamento específico para a recuperação do déficit visual. Métodos Estudo prospectivo de 53 pacientes com hemorragia subaracnóide espontânea (SSAH) por aneurisma rompido. Os pacientes foram avaliados quanto à hemorragia vítrea por fundoscopia indireta com 6 a 12 meses de seguimento. Resultados A idade dos pacientes variou de 17 a 79 anos (média de 45,9 ± 11,7); 39 pacientes eram do sexo feminino (73%) e 14 do sexo masculino (27%). Seis pacientes (11%) apresentaram ST e 83,3% apresentaram perda transitória de consciência durante a ictus. Conclusões Uma avaliação oftalmológica deve ser realizada rotineiramente em pacientes com hemorragia subaracnóide, especialmente naqueles com pior grau neurológico. Além disso, o prognóstico foi ruim em pacientes com ST.

Could outcomes of intracranial aneurysms be better predict using serum creatinine and glomerular filtration rate?

Purpose: To analyze the role of serum creatinine levels as a biomarker of intracranial aneurysm outcomes. Methods: This is a prospective analysis of outcomes of patients with intracranial aneurysm. One hundred forty-seven patients with serum creatinine at admission and 6 months follow up were included. Linear and logistic regressions were used to analyze the data. Modified Rankin scale (mRS) was used to assess outcome. Results: Creatinine level was not directly related to aneurysm outcome nor aneurysm rupture (p > 0.05). However, patients with a glomerular filtration rate (GFR) lower than 72.50 mL·min­1 had an odds ratio (OR) of 3.049 (p = 0.006) for worse outcome. Similarly, aneurysm rupture had an OR of 2.957 (p = 0.014) for worse outcomes. Stepwise selection model selected 4 variables for outcomes prediction: serum creatinine, sex, hypertension and treatment. Hypertensive patients had, on average, an increase in 0.588 in mRS (p = 0.022), while treatment with microsurgery had a decrease in 0.555 (p = 0.038). Conclusions: Patients with higher GFR had better outcomes after 6 months. Patients with higher GFR had better outcomes after 6 months. Creatinine presented an indirect role in GFR values and should be included in models for outcome prediction.

Microsurgery versus embolization: different risk factors for short- and long- term outcomes of patients with ruptured aneurysms

Purpose: To evaluate the risk factors for poor outcomes after surgical and endovascular treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods: Patients with ≥ 18-years of age and aSAH were included, while patients who died within 12 h of admission or lost follow-up were excluded. All participants underwent standardized clinical and radiological assessment on admission and were reassessed at discharge and at 6-months follow-up using the Glasgow Outcome Scale (GOS). Results: Death at discharge was associated with female gender, anterior communication artery (ACoA) aneurysm location and presence of atherosclerotic plaque in the surgical group, and with age in the endovascular group. Both groups had clinical condition on follow-up associated with mFisher score on admission and hypertension. GOS on follow-up was also associated with presence of atherosclerotic plaque and multiple aneurysms in surgical group, and with age in endovascular group. Conclusions: Subjects treated surgically are prone to unfavorable outcomes if atherosclerotic plaques and multiple aneurysms are present. In patients with endovascular treatment, age was the main predictor of clinical outcome.

Eficácia do topiramato como terapia adicional em pacientes com estado epiléptico refratário: uma breve revisão sistemática / Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review

RESUMO Objetivo: Identificar evidências atuais sobre topiramato para o estado de mal epiléptico refratário. Métodos: Foi revisada a literatura para investigar a eficácia do topiramato no tratamento de estado de mal epiléptico refratário. Os termos de busca utilizados foram: "status epilepticus", "refractory", "treatment" e "topiramate". Não se empregaram restrições. Resultados: A busca identificou 487 artigos que descreviam o uso de topiramato para tratamento de estado de mal epiléptico refratário e seus resultados. Relatos de caso, revisões e experimentos em animais foram excluídos. Após exclusão de duplicatas e aplicação dos critérios de inclusão e exclusão, restaram nove estudos. Realizaram-se análises descritivas e qualitativas, com os seguintes resultados: as taxas de resposta, definidas como término de crises até 72 horas após administração de topiramato, variaram entre 27% e 100%. A mortalidade variou de 5,9% a 68%. Desfechos funcionais positivos, definidos como alta hospitalar, volta à funcionalidade basal ou reabilitação, foram documentados por sete estudos, e as taxas variaram entre 4% e 55%. A maioria dos estudos reportou apenas efeitos colaterais leves ou ausentes. Conclusão: Topiramato foi efetivo em abortar estado de mal epiléptico refratário, apresentando baixa mortalidade e boa tolerabilidade. Portanto, topiramato poderia ser uma boa opção como terceira linha para estado de mal epiléptico refratário, porém mais estudos são necessários.

ABSTRACT Objective: To identify current evidence on the use of topiramate for refractory status epilepticus. Methods: We reviewed the literature to investigate the efficacy of topiramate in the treatment of refractory status epilepticus. The search terms used were "status epilepticus", "refractory", "treatment" and "topiramate". No restrictions were used. Results: The search yielded 487 articles that reported using topiramate as a treatment for refractory status epilepticus and its outcomes. Case reports, review articles, and animal experiments were excluded. After excluding duplicates and applying inclusion and exclusion criteria, nine studies were included for analyses. Descriptive and qualitative analyses were performed, and the results were as follows: response rates (defined as termination in-hospital until 72 hours after the administration of topiramate) varied from 27% to 100%. The mortality rate varied from 5.9% to 68%. Positive functional long-term outcomes, defined as discharge, back to baseline or rehabilitation, were documented by seven studies, and the rates ranged between 4% and 55%. Most studies reported no or mild adverse effects. Conclusion: Topiramate was effective in terminating refractory status epilepticus, presented relatively low mortality and was well tolerated. Therefore, topiramate could be a good option as a third-line therapy for refractory status epilepticus, but further studies are necessary.

Pterygopalatine Fossa: Microsurgical Anatomy and its Relevance for Skull Base Surgery

Introduction The purpose of this study was to define the anatomical relationships of the pterygopalatine fossa (PPF) and its operative implications in skull base surgical approaches. Methods Ten cadaveric heads were dissected at the Dianne and M Gazi Yasargil Educational Center MicrosurgicaLaboratory, in Little Rock, AK, USA. The PPF was exposed through an extended dissection with mandible and pterygoid plate removal. Results The PPF has the shape of an inverted cone. Its boundaries are the pterygomaxillary fissure; themaxilla, anteriorly; themedial plate of the pterygoid process, and greater wing of the sphenoid process, posteriorly; the palatine bone,medially; and the body of the sphenoid process, superiorly. Its contents are the maxillary division of the trigeminal nerve and its branches; the pterygopalatine ganglion; the pterygopalatine portion of the maxillary artery (MA) and its branches; and the venous network. Differential diagnosis of PPF masses includes perineural tumoral extension along the maxillary nerve, schwannomas, neurofibromas, angiofibromas, hemangiomas, and ectopic salivary gland tissue. Transmaxillary and transpalatal approaches require extensive resection of bony structures and are narrow in the deeper part of the approach, impairing the surgical vision and maneuverability. Endoscopic surgery solves this problem, bringing the light source to the center of the surgical field, allowing proper visualization of the surgical field, extreme close-ups, and different view angles. Conclusion We provide detailed information on the fossa's boundaries, intercommunications with adjacent structures, anatomy of the maxillary artery, and its variations. It is discussed in the context of clinical affections and surgical approaches of this specific region, including pterygomaxillary disjunction and skull base tumors.

Microsurgical and Endoscopic Anatomy of the Cavernous Sinus

Objective To describe the endoscopic and microsurgical anatomy of the cavernous sinus (CS) with focus on the surgical landmarks in microsurgical anatomy. Materials and methods Ten formalin-fixed central skull base specimens (20 CSs) with silicone-injected carotid arteries were examined through an extended endoscopic transsphenoidal approach. Fifteen formalin-fixed heads were dissected to simulate the surgical position in CS approaches. Results Endoscopic access enables identification of the anterior and posterior surgical corridors. Structures within the CS and on its lateral wall could be visualized and studied, but none of the triangular areas relevant to the transcranial microsurgical anatomy were fully visible through the endoscopic approach. Conclusion The endoscopic approach to the CS is an important surgical technique for the treatment of pathological conditions that affect this region. Correlating endoscopic findings with the conventional (transcranial)microsurgical anatomy is a useful way of applying the established knowledge into a more recent operative technique. Endoscope can provide access to the CS and to the structures it harbors.

Surgical treatment of drug-resistant epilepsy caused by gliomas in eloquent areas: experience report / Tratamento cirúrgico de epilepsias refratárias causadas por gliomas localizados em áreas eloquentes: uma série de casos brasileiros

ABSTRACT Drug-resistant epilepsy associated with central nervous system tumors is generally caused by low grade gliomas. This group of tumors is usually found in brain eloquent areas, such as the insular lobe, rolandic cortex and supplementary motor area and, historically, possess a greater risk of postoperative deficits. Objective: The aim of this investigation was to present our surgical experience on patients with drug-resistant epilepsy caused by gliomas in eloquent areas. We retrospectively investigated variables that impact seizure control, such as tumor location, extent of resection, invasion into the lenticulostriate arteries in the patient, especially those with insular gliomas. Methods: Out of 67 patients with eloquent area brain tumors operated on in our service between 2007 and 2016, 14 patients had symptoms of drug-resistant epilepsy. Volumetric analysis, extent of resection (EOR), type of approach and mapping, among other factors were correlated with the 12-month postoperative seizure outcome. Results: Univariate analysis showed that the factors showing statistical relevance with seizure control were preoperative volume (p = 0.005), EOR (p = 0.028) and postoperative volume (p = 0.030). Conclusion: There was a statistically significant association between the EOR and the Engel score for epilepsy control: an EOR < 70 was associated with Engel II, III, IV and an EOR > 90 was associated with Engel I. Eloquent area gliomas can safely be resected when surgeons use not only microsurgical anatomy concepts but also brain mapping.

RESUMO Epilepsia refratária secundária a tumores cerebrais são geralmente causadas por gliomas de baixo grau. Esse grupo de tumor é frequentemente localizado em áreas eloquentes do cérebro como na insula, córtex rolândico e área motora suplementar; e sua ressecção apresenta alto risco de déficits neurológicos no pós operatório. Objetivo: O objetivo do estudo consiste em apresentar nossa experiência no tratamento cirúrgico de pacientes com epilepsia refratária secundário a gliomas em áreas eloquentes. Métodos: O estudo consiste em investigação retrospectiva de variáveis que interferem no controle de crises, tais como localização do tumor, grau de ressecção, invasão tumoral de artérias lenticulo estriadas, principalmente em gliomas insulares. Dentre 67 pacientes portadores de gliomas em área eloquente operados no período de 2007 a 2016, 14 doentes apresentavam epilepsia refrataria associada. Análise volumétrica do tumor, grau de ressecção, acesso cirúrgico, bem como o uso de mapeamento cortical intraoperatório foram correlacionados com desfecho de controle de crises epilepticas em 12 meses. Resultados: Em análise univariada os fatores relacionados com controle de crises em 12 meses foram volume tumoral pré operatório (p = 0,005), grau de ressecção (p = 0,028) e volume tumoral pós operatório. Conclusão: O grau de ressecção apresentou significância estatística em relação ao controle de crises conforme escala de Engel. Ressecções menores que 70% apresentaram correlação com Engel II, III e IV; enquanto ressecções maiores que 90% apresentaram correção positiva com Engel I. Gliomas em áreas eloquentes podem ser ressecados de forma segura desde que seja realizada por equipe experiente com conhecimento acurado da anatomia microcirúrgica e emprego de mapeamento cortical intraoperatório.

Palsy of the Contralateral Abducens Nerve after Aneurysm Surgery and Temporal Meningioma in the Presence of Petroclival Meningioma: A Case Report

The sixth abducens nerve is subject to injury after rare complications of intracranial hypotension caused by procedures such as dural punctures and spinal surgeries. The purpose of this case report is to discuss the mechanism of nerve palsy in these situations. Therefore, we describe a case of onset of contralateral sixth cranial nerve palsy after intracranial aneurysm and temporal meningioma surgery. Moreover, in this case there is a singularity due to the presence of the petroclival meningioma that amplified the unfolding of the lesion.

O sexto nervo abducente está sujeito a lesões após raros eventos de hipotensão intracraniana gerada por procedimentos como punções de dura-máter e cirurgias de coluna. O propósito deste relato de caso é discutir o mecanismo da paralisia deste nervo nestas situações. Para isso, descrevemos um caso de aparecimento de paresia do sexto nervo craniano contralateral após cirurgia de aneurisma intracraniano e de meningioma temporal. Além do mais, neste caso há uma singularidade em razão da presença do meningioma petroclival contralateral, que amplificou o desdobramento da lesão.

Surgical Treatment of Posterior Circulation Aneurysms ­ Anatomical Study and Surgical Technique

Posterior circulation aneurysms represent 10­15% of intracranial aneurysms. The diagnosis is usually secondary to subarachnoid hemorrhage due to its initial asymptomatic presentation and higher risk of rupture compared with aneurysms in the anterior circulation. The surgical treatment of posterior circulation aneurysms is complex and challenging for neurosurgeons because of the particular anatomy of the posterior circulation with its close relation to the brainstem and cranial nerves and also because of the depth and narrowness of the surgical approach. Aneurysms from different locations have specific anatomical relationships and surgical approaches for better visualization and dissection. Therefore, a detailed anatomy knowledge of the posterior circulation is mandatory for an individualized preoperative planning and good neurological and angiographic outcomes.We selected the main aneurysm sites on the posterior circulation, such as: posterior inferior cerebellar artery, basilar trunk, basilar bifurcation, posterior cerebral artery (PCA) and superior cerebellar artery for a detailed description of the relevant anatomy related to aneurysm, and the main surgical approaches for its surgical treatment. Furthermore, we performed a literature review with the most recent outcomes regarding to the surgical treatment of posterior circulation aneurysms.

Aneurismas de circulação posterior representam de 10­15% dos aneurismas intracranianos. O diagnóstico, frequentemente, é secundário a hemorragia subaracnoide devido à apresentação assintomática na maioria dos casos e ao alto risco de sangramento comparado com aneurismas da circulação anterior. O tratamento cirúrgico de aneurismas de circulação posterior é complexo e desafiador para os neurocirurgiões devido à anatomia particular da região, profundidade do acesso cirúrgico, e relação intima com o tronco encefálico e os nervos cranianos. Aneurismas de diferentes localizações têm diferentes relações anatômicas e, portanto, acessos cirúrgicos específicos para melhor dissecção e visibilização de estruturas. Logo, um conhecimento detalhado de anatomia é mandatório para planejamento operatório individualizado e bons resultados clinico-radiológicos. Foram selecionadas as principais localizações de aneurismas de circulação posterior: Artéria cerebelar póstero-inferior; tronco de artéria basilar, bifurcação de artéria basilar, artéria cerebral posterior, e artéria cerebelar superior para detalhamento anatômico da anatomia relevante. O estudo objetiva realizar uma revisão da literatura dos principais resultados sobre tratamento cirúrgico de aneurismas de circulação posterior, além de descrever os principais pontos anatômicos relevantes à técnica microcirúrgica.

Pilomyxoid Astrocytoma: Case Report

The pilomyxoid astrocytoma (PMA) is a rare glioma recently described as a separate entity, which is generally located on the hypothalamic area. The PMA was previously described as pilocytic astrocytoma (PA) due to similarities shared between them. Recent studies provided a deeper understanding of PMA, setting it as a separate entity, though PMA is still considered by many authors a variant of PA. The PMA is considered to be more aggressive than PA; however, further studies are necessary for a better comprehension of its behavior and, hence, for neurosurgeons and neurologists to get to a consensus about its management. This study presents a 16-year-old female patient who looked for medical assistance complaining of headaches of over 6 months and vomiting for 2 weeks prior to the visit to the doctor. She presented no other symptoms. The physical examination displayed only bilateral papilledema. The magnetic resonance imaging (MRI) scans showed an intraventricular and thalamic lesion composed of solid and cystic material associated with peritumoral edema. The patient underwent ventriculoperitoneal shunt and subtotal resection of the lesion. The histological and immunohistochemical studies showed typical features of PMA. The patient started adjuvant therapy with chemotherapy and radiosurgery. She has been asymptomatic for 9 months and has shown no signs of progression of the disease on the follow-up scans.

O astrocitoma pilomixoide (APM) é um raro glioma, recentemente descrito como uma entidade separada, que geralmente se localiza na região hipotalâmica. Anteriormente, o APM era descrito como astrocitoma pilocítico (AP) devido a características semelhantes que ambos apresentam. Estudos recentes permitiram um melhor entendimento do APM, configurando-o como uma entidade separada, embora o APM ainda seja considerado por muitos autores uma variante do AP. O APM é considerado mais agressivo que o AP; no entanto, mais estudos são necessários para um melhor entendimento do comportamento do tumor e, consequentemente, para que neurocirurgiões e neurologistas cheguem a um consenso sobre sua terapêutica. Este estudo apresenta uma paciente de 16 anos que procurou atendimento médico com queixas de dores de cabeça por mais de 6 meses e vômitos nas 2 semanas antecedentes à visita ao médico. Outros sintomas não eram apresentados. O exame físico revelou apenas papiledema bilateral. As imagens de ressonância magnética mostraram uma lesão intraventricular e hipotalâmica de componentes sólido e cístico associados a edema peritumoral. A paciente foi submetida a derivação ventriculoperitoneal e a ressecção subtotal da lesão. Os estudos histológico e imunohistoquímico demonstraram características típicas de APM. A paciente iniciou terapia adjuvante com quimioterapia e radiocirurgia. A paciente está em acompanhamento por 9 meses e, até o momento, manteve-se assintomática e não houve sinais de progressão da doença nos exames de imagem.

Langerhans Cell Histiocytosis as Cause of Central Diabetes Insipidus: Case Report

Langerhans cell histiocytosis (LCH) is a rare disease of the monocyte-macrophage system, characterized by the aberrant proliferation of specific dendritic cells. The clinical presentation ranges from a single bone lesion to widespread multiorgan involvement. This disease is usually considered to be a disease of childhood; however, the diagnosis is frequently made in adulthood. The course of the disease is fairly unpredictable and varies from spontaneous resolution to progress into a debilitating form, which compromises the vital functions with occasional fatal consequences. Langerhans cell histiocytosis exhibits a predilection for the hypothalamic-pituitary-axis, with diabetes insipidus being the most common endocrine consequence related to the disease, which may be prior to diagnosis or develop at any time during the course of the disease. The diagnosis of LCH should be based on histologic and immunophenotypic examination of a lesional biopsy, although other testing may be done, depending on the symptoms. There is no established, widely agreed-upon treatment of LCH, in general. The treatment depends upon the individual patient and the extent and areas of involvement. The present article aims to describe the case of a 26-year-old male patient whose symptoms started with a headache and occipital bone lesion that progressed later with diabetes insipidus.

A histiocitose de células de Langerhans (HCL) é uma rara doença do sistema monocítico-macrofágico, caracterizada pela proliferação aberrante de células dendríticas específicas. As manifestações clínicas variam de uma única lesão óssea a um acometimento extenso de múltiplos órgãos. Esta doença geralmente é considerada uma doença da infância; no entanto, o diagnóstico é frequentemente feito na idade adulta. O curso da doença é bastante imprevisível e varia de resolução espontânea a progressão para uma forma debilitante, com comprometimento de funções vitais e ocasionais consequências fatais. A HCL exibe uma predileção pelo eixo hipotálamohipofisário, sendo o diabetes insípido a consequência endócrina mais comum relacionada à doença, podendo ser anterior ao diagnóstico ou se desenvolver a qualquer momento durante o curso da doença. O diagnóstico de HCL deve basearse nos exames histológico e imunofenotípico de uma biópsia lesional, embora outros exames possam ser feitos a depender dos sintomas apresentados pelo paciente. Não existe um tratamento estabelecido, amplamente aceito para a HCL, em geral. O tratamento depende individualmente do paciente, da extensão e das áreas de envolvimento. O presente artigo tem como objetivo descrever o caso de um paciente do sexo masculino de 26 anos de idade que iniciou o quadro com uma cefaleia e lesão óssea occipital que evoluiu posteriormente com quadro de diabetes insípido.

The Glymphatic System: A Review

The brain represents 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glialdependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.