A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis.

Despite much effort to improve treatments, patients with malignant glioma still present a very poor prognosis that has not changed significantly in the last decades. In this context, it is crucial to better understand glioma pathogenesis to identify new molecular prognostic subgroups and therapeutic targets. WNT6 was recently identified as a new oncogenic molecule in glioblastoma (GBM), with prognostic value in patients, but the mechanisms underlying WNT6 aberrant expression in glioma are still unknown. WNT6 was overexpressed in a subset of gliomas independently of IDH mutations, 1p/19q codeletion status, and WNT6 gene copy number. Interestingly, WNT6 expression is associated with the DNA methylation levels of particular CpG regions at both the WNT6 promoter and the gene body in glioma patient samples. HOXA9, a transcription factor previously associated with poorer clinical outcome in GBM, was identified as a novel transcriptional regulator of WNT6, activating the WNT/ß-catenin pathway in vitro and in vivo. In various cohorts of glioma patients, mRNA levels of WNT6 and HOXA9 were significantly correlated, extending our in vitro and in vivo findings into the clinical setting. Interestingly, this novel molecular link between WNT6 and HOXA9 was not limited to glioma, as they were co-expressed also in patients with other tumor types. Clinically, WNT6 was a prognostic biomarker of shorter survival in GBM, independently of HOXA9 expression. Concomitant high expression of both WNT6 and HOXA9 identified a subgroup of patients with particularly dismal survival. These findings describe novel WNT6 regulatory mechanisms in GBM, establishing particular DNA methylation patterns and HOXA9 as critical regulators of WNT6 expression in glioma. This HOXA9-WNT6 molecular link supports WNT signaling in GBM cells and is a powerful prognostic biomarker, highlighting the clinical relevance of this axis in patients. Novel therapies targeting WNT6-HOXA9 signaling may thus be useful for this deadly disease.

Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.

PURPOSE: High-grade gliomas (HGG) remain one of the most aggressive tumors, which is primarily due to its diffuse infiltrative nature. Serine proteases and metalloproteases are known to play key roles in cellular migration and invasion mechanisms. SPINT2, also known as HAI-2, is an important serine protease inhibitor that can affect MET signaling. SPINT2 has been found to be frequently downregulated in various tumors, whereby hypermethylation of its promoter appears to serve as a common mechanism. Here, we assessed the clinical relevance of SPINT2 expression and promoter hypermethylation in pediatric and adult HGG and explored its functional role. METHODS: A series of 371 adult and 77 pediatric primary HGG samples was assessed for SPINT2 protein expression (immunohistochemistry) and promoter methylation (methylation-specific PCR) patterns. After SPINT2 knockdown and knock-in in adult and pediatric HGG cell lines, a variety of in vitro assays was carried out to determine the role of SPINT2 in glioma cell viability and invasion, as well as their mechanistic associations with metalloprotease activities. RESULTS: We found that SPINT2 protein expression was frequently absent in adult (85.3%) and pediatric (100%) HGG samples. The SPINT2 gene promoter was found to be hypermethylated in approximately half of both adult and pediatric gliomas. Through functional assays we revealed a suppressor activity of SPINT2 in glioma cell proliferation and viability, as well as in their migration and invasion. These functions appear to be mediated in part by MMP2 expression and activity. CONCLUSIONS: We conclude that dysregulation of SPINT2 is a common event in both pediatric and adult HGG, in which SPINT2 may act as a tumor suppressor.

Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review

Oligodendrogliomas are infiltrative tumors of the central nervous systemconsidered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36- year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.

Brain biopsy in suspected non-neoplastic neurological disease.

Brain biopsy has a well-established role in the diagnosis of CNS neoplasia. Nevertheless, despite being essential for the diagnosis of some benign neurological diseases, little consensus exists regarding its indications for disease diagnosis and patient orientation. Our aim was to assess brain biopsy diagnostic yield in patients with neurological deterioration of unknown etiology, to identify the clinical characteristics associated with an increased likelihood of achieving a diagnostic biopsy as well as the characteristics linked to a particular diagnosis. METHODS: A retrospective analysis of 62 consecutive brain biopsies performed at a single tertiary care center between January 2004 and December 2015 for suspected non-neoplastic neurological disease was performed. The clinical presentation, imaging, and laboratory results were collected and compared between diagnostic groups. RESULTS: Sixty-eight percent of the biopsies led to a definitive diagnosis. The most common histological diagnosis was central nervous system lymphoma (eight cases), followed by astrocytoma, demyelinating disease, and progressive multifocal leukoencephalopathy (four cases each). No clinical characteristics were found to predict a diagnostic biopsy or to correlate with a specific diagnosis. Importantly, a distinct diagnosis from the initially suspected was achieved in 52% of cases and biopsy findings led to a change of therapeutic orientation in 78% of the cases. CONCLUSIONS: Our results suggest that brain biopsies have a significant impact on patient management and should be considered early in selected cases in which less invasive testing was unable to reach a definitive diagnosis.

Superior Sagittal Sinus Invasion by Malignant Glioma: Case Report and Literature Review

Anaplastic oligodendrogliomas (AOs) correspond to 23% of all oligodendrogliomas. They correspond to a tumor with malignant histological characteristics, focal or diffuse, associated with a worse prognosis. In the present case report, we describe the case of a 30-year-old female submitted to resection of a right parietal lesion whose histology showed to be an AO. She underwent complementary treatment with chemotherapy and radiotherapy according to the Roger Stupp protocol. Four years after the initial diagnosis, there was tumor recurrence within the superior sagittal sinus, with no evidence of recurrence elsewhere. In the literature, we have found no similar published case reinforcing the rarity of this condition.

Continuous quadratus lumborum type II block in partial nephrectomy / Bloqueio do quadrado lombar tipo II contínuo para analgesia pós-operatória de nefrectomia parcial

Abstract Background and objectives: Quadratus lumborum block was first described in 2007 and currently there are descriptions of its achievement through four different injection points. This blockage provides abdominal wall and visceral analgesia, and one of its mechanisms is the dispersion of the local anesthetic into the paravertebral space. We describe the performance of a continuous quadratus lumborum type II block for postoperative analgesia in a partial nephrectomy. Case report: A 64-year-old woman, scheduled for partial left laparoscopic nephrectomy. During the procedure, due to technical difficulties, an incision was made in the left flank to facilitate the surgical approach. In the early postoperative period, a continuous quadratus lumborum type II block was performed using ultrasonography as part of the multimodal analgesic strategy. Initially, 20 ml of 0.2% ropivacaine was administered and 3 cm of catheter were introduced into the interfascial space. Subsequently, a continuous infusion of 5.2 mL.h−1 of 0.2% ropivacaine was given for 48 hours. In the first 24 postoperative hours, the patient reported no pain at rest or on movement. In the following 24 h, she was free of pain at rest and only a slight pain (2/10) on movement. Conclusions: Continuous quadratus lumborum type II block was an effective postoperative analgesic option. Blocking of somatic nerves and visceral afferent pathways provided abdominal and visceral wall analgesia, allowing the reduction of opioid consumption. We consider relevant to explore the analgesic capacity of the quadratus lumborum block and its different approaches, as well as the possibility of it becoming an alternative in patients scheduled for kidney surgery.

Resumo Justificativa e objetivos: O bloqueio do quadrado lombar foi descrito pela primeira vez em 2007 e atualmente existem descrições da sua realização através de quatro pontos de injeção. Esse bloqueio promove analgesia da parede abdominal e analgesia visceral e um de seus mecanismos é a dispersão do anestésico local para o espaço paravertebral. Descrevemos a realização do bloqueio do quadrado lombar tipo II contínuo para analgesia pós-operatória numa nefrectomia parcial. Relato de caso: Mulher de 64 anos, agendada para nefrectomia parcial à esquerda por via laparoscópica. Durante o procedimento, por dificuldades técnicas, foi feita uma incisão no flanco esquerdo para facilitar a abordagem cirúrgica. No pós-operatório imediato, fez-se o bloqueio do quadrado lombar tipo II contínuo, recorrendo-se a ultrassonografia, como parte da estratégia analgésica multimodal. Inicialmente foram administrados 20 ml de ropivacaína 0,2% e introduzidos 3 cm de cateter no espaço interfascial. Posteriormente, colocou-se uma perfusão contínua de 5,2 mL.h−1 de ropivacaína 0,2% durante 48 horas. Nas primeiras 24 horas de pós-operatório, a paciente não referiu dor em repouso ou com movimento. Nas 24 horas seguintes, manteve-se sem dor em repouso e apenas com dor ligeira (2/10) com o movimento. Conclusões: A realização do bloqueio quadrado lombar tipo II contínuo foi uma opção analgésica pós-operatória eficaz. O bloqueio de nervos somáticos e das vias aferentes viscerais promoveu analgesia da parede abdominal e visceral, permitiu reduzir o consumo de opioides. Consideramos relevante explorar a capacidade analgésica do bloqueio do quadrado lombar e suas diferentes abordagens, bem como a possibilidade de se tornar uma opção em doentes propostos para cirurgia renal.

Superior gluteal nerve: a new block on the block? / Nervo glúteo superior: um novo bloqueio a caminho?

Abstract Background and objectives The superior gluteal nerve is responsible for innervating the gluteus medius, gluteus minimus and tensor fascia latae muscles, all of which can be injured during surgical procedures. We describe an ultrasound-guided approach to block the superior gluteal nerve which allowed us to provide efficient analgesia and anesthesia for two orthopedic procedures, in a patient who had significant risk factors for neuraxial techniques and deep peripheral nerve blocks. Clinical report An 84-year-old female whose regular use of clopidogrel contraindicated neuraxial techniques or deep peripheral nerve blocks presented for urgent bipolar hemiarthroplasty in our hospital. Taking into consideration the surgical approach chosen by the orthopedic team, we set to use a combination of general anesthesia and superficial peripheral nerve blocks (femoral, lateral cutaneous of thigh and superior gluteal nerve) for the procedure. A month and a half post-discharge the patient was re-admitted for debriding and correction of suture dehiscence; we performed the same blocks and light sedation. She remained comfortable in both cases, and reported no pain in the post-operative period. Conclusions Deep understanding of anatomy and innervation empowers anesthesiologists to solve potentially complex cases with safer, albeit creative, approaches. The relevance of this block in this case arises from its innervation of the gluteus medius muscle and posterolateral portion of the hip joint. To the best of our knowledge, this is the first report of an ultrasound-guided superior gluteal nerve block with an analgesic and anesthetic goal, which was successfully achieved.

Resumo Justificativa e objetivos O nervo glúteo superior é responsável pela inervação dos músculos glúteo médio, glúteo mínimo e tensor da fáscia lata, todos podem ser lesados durante procedimentos cirúrgicos. Descrevemos uma abordagem guiada por ultrassom para bloqueio do nervo glúteo superior, o que nos permitiu fornecer analgesia e anestesia eficientes para dois procedimentos ortopédicos a uma paciente que apresentava fatores de risco significativos para técnicas neuraxiais e bloqueios profundos de nervos periféricos. Relato de caso Paciente do sexo feminino, 84 anos, cujo uso regular de clopidogrel contraindicava técnicas neuraxiais ou bloqueios profundos de nervos periféricos, apresentou-se para hemiartroplastia bipolar urgente em nosso hospital. Levando em consideração a abordagem cirúrgica escolhida pela equipe de ortopedia, estabelecemos o uso de uma combinação de anestesia geral e bloqueios superficiais de nervos periféricos (femoral, cutâneo lateral da coxa e nervo glúteo superior) para o procedimento. Um mês e meio após a alta, a paciente foi readmitida para desbridamento e correção da deiscência de sutura quando fizemos os mesmos bloqueios e sedação leve. A paciente permaneceu confortável em ambos os casos, sem queixa de dor no período pós-operatório. Conclusões A compreensão profunda da anatomia e da inervação capacita os anestesiologistas a resolver casos potencialmente complexos com abordagens mais seguras, até criativas. A relevância desse bloqueio neste caso resulta da sua inervação do músculo glúteo médio e da porção posterolateral da articulação do quadril. De acordo com nossa pesquisa, este é o primeiro relato de um bloqueio do nervo glúteo superior guiado por ultrassom com objetivo analgésico e anestésico que foi obtido com sucesso.

Quadratus lumborum block: are we aware of its side effects? A report of 2 cases / Bloqueio do quadrado lombar: estamos cientes de seus efeitos colaterais? Relato de dois casos

Abstract Background and objectives The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication. Clinical reports We report two cases in which we performed a quadratus lumborum type II block and general anesthesia for total gastrectomy and right hemicolectomy. There were no noteworthy events while performing the block and inducing general anesthesia, but within 30-40 min serious hypotension and tachycardia were noted. As other motives for hypotension were ruled out, the event was interpreted as block-induced sympatholysis due to cephalad dispersion of the local anesthetic to the paravertebral and epidural space, and successfully managed with ephedrine and increase of the crystalloid infusion rate. Conclusions The quadratus Lumborum block is safe to execute and provides effective abdominal wall and visceral analgesia. However, the possibility of eliciting undesired episodes should prompt caution when performing this block and practitioners should thereafter remain vigilant. Questions regarding ideal dosing, volumes, timing of block and pertinence of catheters remain to be answered.

Resumo Justificativa e objetivos O bloqueio do quadrado lombar foi primeiramente descrito em 2007 e tem como objetivo o bloqueio dos mesmos nervos envolvidos no bloqueio do plano transverso abdominal, ao atingir algumas inervações viscerais, bem como devido à maior proximidade com o neuroeixo e cadeia simpática. Dada a sua versatilidade, temos usado esse bloqueio com sucesso em uma grande variedade de procedimentos. Relatamos dois casos nos quais acreditamos que a dispersão do anestésico local pode ter levado a uma complicação não descrita previamente. Relatos clínicos Relatamos dois casos nos quais realizamos o bloqueio do quadrado lombar tipo II e anestesia geral para gastrectomia total e hemicolectomia direita. Não houve eventos notáveis durante o bloqueio e a indução da anestesia geral, mas, dentro de 30 a 40 minutos, observamos grave hipotensão e taquicardia. Como outros motivos para a hipotensão foram descartados, o evento foi interpretado como simpatólise induzida pelo bloqueio devido à dispersão cefálica do anestésico local para os espaços paravertebral e epidural e tratado com sucesso com efedrina e aumento da taxa de infusão de cristaloides. Conclusões O bloqueio do quadrado lombar oferece segurança na execução e fornece analgesia eficaz à parede abdominal e vísceras. Porém, a possibilidade de provocar episódios indesejáveis requer cautela em sua execução e, por conseguinte, os médicos precisam estar atentos. As questões relacionadas à dosagem ideal, aos volumes, ao tempo de bloqueio e à pertinência dos cateteres permanecem indefinidas.

[Continuous quadratus lumborum type II block in partial nephrectomy]. / Bloqueio do quadrado lombar tipo II contínuo para analgesia pós­operatória de nefrectomia parcial.

BACKGROUND AND OBJECTIVES: Quadratus lumborum block was first described in 2007 and currently there are descriptions of its achievement through four different injection points. This blockage provides abdominal wall and visceral analgesia, and one of its mechanisms is the dispersion of the local anesthetic into the paravertebral space. We describe the performance of a continuous quadratus lumborum type II block for postoperative analgesia in a partial nephrectomy. CASE REPORT: A 64-year-old woman, scheduled for partial left laparoscopic nephrectomy. During the procedure, due to technical difficulties, an incision was made in the left flank to facilitate the surgical approach. In the early postoperative period, a continuous quadratus lumborum type II block was performed using ultrasonography as part of the multimodal analgesic strategy. Initially, 20ml of 0.2% ropivacaine was administered and 3cm of catheter were introduced into the interfascial space. Subsequently, a continuous infusion of 5.2mL.h-1 of 0.2% ropivacaine was given for 48hours. In the first 24 postoperative hours, the patient reported no pain at rest or on movement. In the following 24hours, she was free of pain at rest and only a slight pain (2/10) on movement. CONCLUSIONS: Continuous quadratus lumborum type II block was an effective postoperative analgesic option. Blocking of somatic nerves and visceral afferent pathways provided abdominal and visceral wall analgesia, allowing the reduction of opioid consumption. We consider relevant to explore the analgesic capacity of the quadratus lumborum block and its different approaches, as well as the possibility of it becoming an alternative in patients scheduled for kidney surgery.

Type II Quadratus Lumborum block for a sub-total gastrectomy in a septic patient / Bloqueio do quadrado lombar tipo II para uma gastrectomia subtotal em um paciente séptico

Abstract Introduction and objectives: Quadratus Lumborum block was recently described and has already shown good results as an analgesic technique in abdominal surgeries, having the potential to significantly reduce opioids consumption and be a valid alternative to epidural catheter. We performed a type II Quadratus Lumborum block for analgesia in a septic patient having a sub-total gastrectomy. Case report: An 80 year-old, ASA III, male patient, weighting 50 kg, with a history of arterial hypertension and hypercholesterolemia, diagnosed with sepsis due to purulent peritonitis was submitted to an open laparotomy. Bilateral ultrasound-guided type II Quadratus Lumborum block was performed before surgery, using 10 mL of levobupivacaine 0.25% and 5 mL of mepivacaine 1%, per side. Pain relief was achieved 5 minutes after injection and the patient referred no pain in the immediate postoperative period. Discussion: Type II Quadratus Lumborum block may be considered a valid alternative for postoperative analgesia in a septic patient undergoing major abdominal surgery with some relative contraindications to epidural catheter placement. It allowed us to achieve excellent pain management avoiding opioids usage. However, more reports are still needed to properly access its usefulness.

Resumo Introdução e objetivo: O bloqueio do quadrado lombar (QL) foi descrito recentemente e já mostrou bons resultados como técnica analgésica em cirurgias abdominais, com potencial para reduzir significativamente o consumo de opioides e ser uma opção válida ao cateter peridural. Fizemos um bloqueio do QL tipo II para analgesia em um paciente séptico para gastrectomia subtotal. Relato de caso: Paciente do sexo masculino, 80 anos de, ASA III, 50 kg, com história de hipertensão arterial e hipercolesterolemia, diagnosticado com sepsis devido a peritonite purulenta, foi submetido a uma laparotomia aberta. O bloqueio bilateral do QL tipo II guiado por ultrassom foi feito antes da cirurgia com 10 mL de levobupivacaína a 0,25% e 5 mL de mepivacaína a 1%, por lado. O alívio da dor foi obtido em 5 minutos após a injeção e o paciente não referiu dor no pós-operatório imediato. Discussão: O bloqueio do quadrado lombar (QL) tipo II pode ser considerado uma opção válida para analgesia no pós-operatório em um paciente séptico submetido a cirurgia abdominal de grande porte, com algumas contraindicações relativas à colocação do cateter peridural. Permitiu-nos obter um excelente manejo da dor e evitar o uso de opioides. Contudo, mais relatos ainda são necessários para avaliar corretamente a sua utilidade.

[Quadratus lumborum block: are we aware of its side effects? A report of 2 cases]. / Bloqueio do quadrado lombar: estamos cientes de seus efeitos colaterais? Relato de dois casos.

BACKGROUND AND OBJECTIVES: The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication. CLINICAL REPORTS: We report two cases in which we performed a quadratus lumborum type II block and general anesthesia for total gastrectomy and right hemicolectomy. There were no noteworthy events while performing the block and inducing general anesthesia, but within 30-40min serious hypotension and tachycardia were noted. As other motives for hypotension were ruled out, the event was interpreted as block-induced sympatholysis due to cephalad dispersion of the local anesthetic to the paravertebral and epidural space, and successfully managed with ephedrine and increase of the crystalloid infusion rate. CONCLUSIONS: The quadratus Lumborum block is safe to execute and provides effective abdominal wall and visceral analgesia. However, the possibility of eliciting undesired episodes should prompt caution when performing this block and practitioners should thereafter remain vigilant. Questions regarding ideal dosing, volumes, timing of block and pertinence of catheters remain to be answered.

[Superior gluteal nerve: a new block on the block?] / Nervo glúteo superior: um novo bloqueio a caminho?

BACKGROUND AND OBJECTIVES: The superior gluteal nerve is responsible for innervating the gluteus medius, gluteus minimus and tensor fascia latae muscles, all of which can be injured during surgical procedures. We describe an ultrasound-guided approach to block the superior gluteal nerve which allowed us to provide efficient analgesia and anesthesia for two orthopedic procedures, in a patient who had significant risk factors for neuraxial techniques and deep peripheral nerve blocks. CLINICAL REPORT: An 84-year-old female whose regular use of clopidogrel contraindicated neuraxial techniques or deep peripheral nerve blocks presented for urgent bipolar hemiarthroplasty in our hospital. Taking into consideration the surgical approach chosen by the orthopedic team, we set to use a combination of general anesthesia and superficial peripheral nerve blocks (femoral, lateral cutaneous of thigh and superior gluteal nerve) for the procedure. A month and a half post-discharge the patient was re-admitted for debriding and correction of suture dehiscence; we performed the same blocks and light sedation. She remained comfortable in both cases, and reported no pain in the post-operative period. CONCLUSIONS: Deep understanding of anatomy and innervation empowers anesthesiologists to solve potentially complex cases with safer, albeit creative, approaches. The relevance of this block in this case arises from its innervation of the gluteus medius muscle and posterolateral portion of the hip joint. To the best of our knowledge, this is the first report of an ultrasound-guided superior gluteal nerve block with an analgesic and anesthetic goal, which was successfully achieved.

[Type II Quadratus Lumborum block for a sub-total gastrectomy in a septic patient]. / Bloqueio do quadrado lombar tipo II para uma gastrectomia subtotal em um paciente séptico.

INTRODUCTION AND OBJECTIVES: Quadratus Lumborum block was recently described and has already shown good results as an analgesic technique in abdominal surgeries, having the potential to significantly reduce opioids consumption and be a valid alternative to epidural catheter. We performed a type II Quadratus Lumborum block for analgesia in a septic patient having a sub-total gastrectomy. CASE REPORT: An 80 year-old, ASA III, male patient, weighting 50kg, with a history of arterial hypertension and hypercholesterolemia, diagnosed with sepsis due to purulent peritonitis was submitted to an open laparotomy. Bilateral ultrasound-guided type II Quadratus Lumborum block was performed before surgery, using 10mL of levobupivacaine 0.25% and 5mL of mepivacaine 1%, per side. Pain relief was achieved 5minutes after injection and the patient referred no pain in the immediate postoperative period. DISCUSSION: Type II Quadratus Lumborum block may be considered a valid alternative for postoperative analgesia in a septic patient undergoing major abdominal surgery with some relative contraindications to epidural catheter placement. It allowed us to achieve excellent pain management avoiding opioids usage. However, more reports are still needed to properly access its usefulness.

Sphenopalatine ganglion block for postdural puncture headache in ambulatory setting / Bloqueio do gânglio esfenopalatino para cefaleia pós-punção dural em contexto de ambulatório

Abstract Background and objectives: Postdural puncture headache (PDPH) is a common complication following subarachnoid blockade and its incidence varies with the size of the needle used and the needle design. Suportive therapy is the usual initial approach. Epidural blood patch (EBP) is the gold-standard when supportive therapy fails but has significant risks associated. Sphenopalatine ganglion block (SPGB) may be a safer alternative. Case report: We observed a 41 year-old female patient presenting with PDPH after a subarachnoid blockade a week before. We administrated 1 l of crystalloids, Dexamethasone 4 mg, parecoxib 40 mg, acetaminophen 1 g and caffeine 500 mg without significant relief after 2 hours. We performed a bilateral SPGB with a cotton-tipped applicator saturated with 0.5% Levobupivacaine under standard ASA monitoring. Symptoms relief was reported 5 minutes after the block. The patient was monitored for an hour after which she was discharged and prescribed acetaminophen 1 g and ibuprofen 400 mg every 8 hours for the following 2 days. She was contacted on the next day and again after a week reporting no pain in both situation. Conclusions: SPGB may attenuate cerebral vasodilation induced by parasympathetic stimulation transmitted through neurons that have synapses in the sphenopalatine ganglion. This would be in agreement with the Monro-Kellie concept and would explain why caffeine and sumatriptan can have some effect in the treatment of PDPH. Apparently, SPGB has a faster onset than EBP with better safety profile. We suggest that patients presenting with PDPH should be considered primarily for SPGB. Patients may have a rescue EBP if needed.

Resumo Justificativa e objetivos: Cefaleia pós-punção dural (CPPD) é uma complicação comum após bloqueio subaracnoideo e sua incidência varia de acordo com o tamanho e desenho da agulha usada. Geralmente, a terapia de apoio é a abordagem inicial. O tampão sanguíneo peridural (TSP) é o padrão de terapia quando a terapia de apoio falha, mas tem riscos significativos associados. O bloqueio do gânglio esfenopalatino (BGEP) pode ser uma opção mais segura. Relato de caso: Atendemos uma paciente de 41 anos, com CPPD após bloqueio subaracnoideo uma semana antes. Administramos cristaloides (1 L), dexametasona (4 mg), parecoxib (40 mg), acetaminofeno (1 g) e cafeína (500 mg), sem alívio significativo após 2 horas. Fizemos um bloqueio bilateral do gânglio esfenopalatino, com um aplicador com ponta de algodão saturada com levobupivacaína a 0,5% sob monitoração padrão ASA. O alívio dos sintomas foi relatado 5 minutos após o bloqueio. A paciente foi monitorada por uma hora e depois recebeu alta com prescrição de acetaminofeno (1 g) e ibuprofeno (400 mg) a cada 8 horas para os dois dias seguintes. A paciente foi contatada no dia seguinte e novamente após uma semana e, em ambos os contatos, relatou não sentir dor. Conclusões: O BGEP pode ter atenuado a vasodilatação cerebral induzida pelo estímulo parassimpático transmitido através dos neurônios que têm sinapses no gânglio esfenopalatino. Esse mecanismo estaria de acordo com o conceito de Monro-Kellie e explicaria por que a cafeína e o sumatriptano podem ter algum efeito no tratamento da CPPD. Aparentemente, o BGEP tem um início mais rápido do que o do TSP, com um melhor perfil de segurança. Sugerimos que os pacientes que se apresentam com CPPD devam ser considerados primeiro para BGEP. Os pacientes podem ser submetidos a um TSP de resgate, caso necessário.

[Sphenopalatine ganglion block for postdural puncture headache in ambulatory setting]. / Bloqueio do gânglio esfenopalatino para cefaleia pós­punção dural em contexto de ambulatório.

BACKGROUND AND OBJECTIVES: Postdural puncture headache (PDPH) is a common complication following subarachnoid blockade and its incidence varies with the size of the needle used and the needle design. Supportive therapy is the usual initial approach. Epidural blood patch (EBP) is the gold-standard when supportive therapy fails but has significant risks associated. Sphenopalatine ganglion block (SPGB) may be a safer alternative. CASE REPORT: We observed a 41 year-old female patient presenting with PDPH after a subarachnoid blockade a week before. We administrated 1l of crystalloids, Dexamethasone 4mg, parecoxib 40mg, acetaminophen 1g and caffeine 500mg without significant relief after 2hours. We performed a bilateral SPGB with a cotton-tipped applicator saturated with 0.5% Levobupivacaine under standard ASA monitoring. Symptoms relief was reported 5minutes after the block. The patient was monitored for an hour after which she was discharged and prescribed acetaminophen 1g and ibuprofen 400mg every 8hours for the following 2 days. She was contacted on the next day and again after a week reporting no pain in both situations. CONCLUSIONS: SPGB may attenuate cerebral vasodilation induced by parasympathetic stimulation transmitted through neurons that have synapses in the sphenopalatine ganglion. This would be in agreement with the Monro-Kellie concept and would explain why caffeine and sumatriptan can have some effect in the treatment of PDPH. Apparently, SPGB has a faster onset than EBP with better safety profile. We suggest that patients presenting with PDPH should be considered primarily for SPGB. Patients may have a rescue EBP if needed.

Surgical Management of Ruptured Posterior Circulation Aneurysms ­ A Single Center Experience

Objective The treatment of ruptured aneurysms of the posterior circulation is a controversy in neurosurgery. The aim of this work is to describe the experience and results of the early surgical treatment of this pathology at Centro Hospitalar do Porto. Method We retrospectively analyzed the medical records of all patients aged over 18 who, in the period between 1999­2013, were admitted to our center with the diagnosis of ruptured saccular posterior circulation aneurysm. The patients were clinically staged at admission using the Hunt & Hess (H&H) scale. The modified Glasgow Outcome Scale (mGOS) was used to assess the outcome at discharge and after 6 months. Results Between 1999­2013, 59 patients underwent surgery for ruptured posterior circulation aneurysms. Eighty percent of the patients were female, and their average age was 58.7 years. Posterior-inferior cerebellar artery aneurysms accounted for 49.2% of surgeries, while basilar aneurysms accounted for 28.8%. Upon admission, 86.4% of patients were classified as H&H1­3, and 13.6% as H&H4­5. The outcomes at discharge and at 6 months were as follows: at discharge, mGOS1 in 5.1%, mGOS2­3 in 18.6%, and mGOS4­5 in 76.3%; at 6 months, mGOS1 in 10.2%, mGOS2­3 in 10.2%, and mGOS4­5 in 79.6%. There was a statistically significant correlation between basilar aneurysms and worse outcomes (p » 0.011). No correlation was found between the values of the H&H scale upon admission and outcome. Conclusions The functional outcome of our group of patients is mainly in line with what is described in other series from the literature. However, there is a trend toward lower mortality but higher morbidity rates.

Objetivo O tratamento dos aneurismas rotos da circulação posterior é uma controvérsia neurocirúrgica. Pretende-se com este trabalho relatar a experiência e os resultados do tratamento cirúrgico precoce desta patologia no Centro Hospitalar do Porto. Métodos Foram analisados retrospectivamente os processos clínicos dos pacientes com idade > 18 anos que, no período entre 1999­2013, foram admitidos no nosso centro com o diagnóstico de aneurisma sacular roto da circulação posterior. Utilizou-se a escala de Hunt & Hess (H&H) para aferir a gravidade clínica dos pacientes, e a Escala de Outcome de Glagow modificada (mGOS) para aferir o outcome dos pacientes à data da alta e aos 6 meses. Resultados Entre 1999­2013, foram operados 59 pacientes com aneurismas rotos da circulação posterior. Oitenta por centro dos pacientes eram do sexo feminino, com uma média de idade média de 58.7 anos. Aneurismas da artéria cerebelosa posteroinferior foram responsáveis por 49,2% das cirurgias, ao passo que os da artéria basilar, por 28,8%. À admissão, 86,4% dos pacientes eram H&H1­3, e 13,6%, H&H4­5. O outcome à data da alta e aos 6 meses foi o seguinte: à data de alta, mGOS1 em 5,1%, mGOS2­3 em 18,6%, e mGOS4­5 em 76,3%; aos 6 meses, mGOS1 em 10,2%, mGOS2­ 3 em 10,2%, e mGOS4­5 em 79,6%. Verificou-se uma correlação estatisticamente significativa entre aneurismas da basilar e um pior outcome (p » 0,011). Não se verificou qualquer correlação entre os valores da escala de H&H à admissão e o outcome. Conclusões O outcome funcional do nosso grupo de pacientes está em linha com o descrito noutras séries da literatura. Contudo, destaca-se uma tendência para uma mortalidade mais baixa, mas uma morbilidade mais alta no nosso grupo de pacientes.

Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas.

BACKGROUND: Glioblastomas (GBM) present a high cellular heterogeneity with conspicuous necrotic regions associated with hypoxia, which is related to tumor aggressiveness. GBM tumors exhibit high glycolytic metabolism with increased lactate production that is extruded to the tumor microenvironment through monocarboxylate transporters (MCTs). While hypoxia-mediated regulation of MCT4 has been characterized, the role of MCT1 is still controversial. Thus, we aimed to understand the role of hypoxia in the regulation of MCT expression and function in GBM, MCT1 in particular. METHODS: Expression of hypoxia- and glycolytic-related markers, as well as MCT1 and MCT4 isoforms was assessed in in vitro and in vivo orthotopic glioma models, and also in human GBM tissues by immunofluorescence/immunohistochemistry and Western blot. Following MCT1 inhibition, either pharmacologically with CHC (α-cyano-4-hydroxynnamic acid) or genetically with siRNAs, we assessed GBM cell viability, proliferation, metabolism, migration and invasion, under normoxia and hypoxia conditions. RESULTS: Hypoxia induced an increase in MCT1 plasma membrane expression in glioma cells, both in in vitro and in vivo models. Additionally, treatment with CHC and downregulation of MCT1 in glioma cells decreased lactate production, cell proliferation and invasion under hypoxia. Moreover, in the in vivo orthotopic model and in human GBM tissues, there was extensive co-expression of MCT1, but not MCT4, with the GBM hypoxia marker CAIX. CONCLUSION: Hypoxia-induced MCT1 supports GBM glycolytic phenotype, being responsible for lactate efflux and an important mediator of cell survival and aggressiveness. Therefore, MCT1 constitutes a promising therapeutic target in GBM.

Loss of WNK2 expression by promoter gene methylation occurs in adult gliomas and triggers Rac1-mediated tumour cell invasiveness.

The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours. Following experimental depletion in cell lines, WNK2 was further found to control GTP-loading of Rac1, a signalling guanosine triphosphatase involved in cell migration and motility. Here we show that WNK2 promoter methylation also occurs in 17.5% (29 out of 166) of adult gliomas, whereas it is infrequent in its paediatric forms (1.6%; 1 out of 66). Re-expression of WNK2 in glioblastoma cells presenting WNK2 gene silencing reduced cell proliferation in vitro, tumour growth in vivo and also cell migration and invasion, an effect correlated with reduced activation of Rac1. In contrast, when endogenous WNK2 was depleted from glioblastoma cells with unmethylated WNK2 promoter, changes in cell morphology, an increase in invasion and activation of Rac1 were observed. Together, these results validate the WNK2 gene as a recurrent target for epigenetic silencing in glia-derived brain tumours and provide first mechanistic evidence for a tumour-suppressing role of WNK2 that is related to Rac1 signalling and tumour cell invasion and proliferation.

Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets.

BACKGROUND: Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. METHODS: MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. RESULTS: MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. CONCLUSIONS: This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.