Update in Cushing disease: What the neurosurgeon has to KNOW, on behalf of the EANS skull base section.

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma. Research question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management. Material and methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts. Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD. Discussion and conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long.

Extradural en-plaque spinal lipomatous meningioma: A case report and literature review.

BACKGROUND: Extradural spinal meningiomas are rare, and few appear as lipomatous meningiomas in an "en-plaque" form. The transitional fibroblastic subtype, with lipid accumulation within the tumoral cells, is typically more aggressive and surgically challenging to resect. CASE DESCRIPTION: A 42-year-old male presented with neck pain and progressive paresthesias in both upper extremities. Based on the radiological findings, the tentative preoperative diagnosis was lymphoma. However, the biopsy confirmed a meningioma. The patient underwent a combined extradural anterior and posterior approach, resulting in full tumor resection. Histopathologically, the final report documented a lipomatous meningioma. CONCLUSION: Extradural spinal lipomatous meningiomas (i.e., "en-plaque") are rare and typically result in rapid clinical deterioration. The radiological diagnosis may be difficult, while ultrasonography helps to define their extradural location facilitating planning for gross total anterior/posterior excision where indicated.

Atypical bilateral cerebellopontine angle medulloblastoma: differential diagnosis, immunohistochemical features and radiological presentation.

Medulloblastoma (MB) is a highly aggressive soft tissue neoplasm, classified as a primitive neuroectodermal tumor. It is the most common posterior fossa tumor in children, but occurs rarely in adults. MB accounts for approximately 20% of all primary central nervous system (CNS) tumors of childhood, while its incidence is around 1% of adult brain tumors. Most often it occurs in the cerebellum. We report a case of multicentric MB involving the bilateral cerebellopontine angle (CPA) and right cerebellar hemisphere. The tumor showed isointensity on T1/T2-weighted images, and slight hyperintensity on T2-weighted fluid-attenuated inversion-recovery (FLAIR) images. The MB had restricted diffusion on diffusion-weighted images (DWI). It was not easy to make an accurate diagnosis before biopsy. The lesion in our patient presented with atypical MR image features of medulloblastoma. To our knowledge, this is the first case of bilateral CPA MB.

Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone.

Glioblastoma is the most common primary brain tumor. Despite multimodality therapy with aggressive microsurgical resection and adjuvant chemotherapy and radiotherapy, the median survival is below 15 months. Glioblastomas are heterogeneous tumors with high resistance to most chemotherapeutic drugs. According to reliable evidence, YKL-40, one of the best investigated chitinase-like protein, may facilitate invasion, migration and angiogenesis, and could be also responsible for temozolomide resistance in glioblastoma, thus conferring a dismal prognosis. Previous studies have demonstrated that glioblastoma stem cells give rise to endothelial cells through an YKL-40 influence. Such factor is closely related to the subventricular zone. This review focuses on the most recent theories involving the possible relationship between topographic gliomagenesis related to the subventricular zone and YKL-40..

Meningioma Associated with Brain Aneurysm: Report of Two Cases.

The occurrence of brain tumors together with aneurysms has been considered as an uncommon phenomenon. However, its incidence may be underestimated. This coexistence is a diagnostic challenge, but also a therapeutic one as no consensus has been reached. We report two cases of a 71 and 67 years old patient with a meningioma and aneurysm: one noticed and treated before with good outcome and the other without treatment before surgery with fatal outcome. The different outcome of these patients shows the importance of vascular study in surgical planning. Treatments options are changing and although some authors think the pathology that causes symptoms should be treated first, endovascular treatment of the aneurysm is a safe option to prevent aneurysm rupture during surgery.

Multicentric spinal cord and brain glioblastoma without previous craniotomy.

BACKGROUND: Glioblastoma multiforme (GBS) is a highly malignant glioma that rarely presents as an infratentorial tumor. Multicentric gliomas lesions are widely separated in site and/or time and its incidence has been reported between 0.15 and 10%. Multicentric gliomas involving supratentorial and infratentorial region are even more rare. In most cases, infratentorial disease is seen after surgical manipulation or radiation therapy and is usually located in the cerebellum or cervical region. CASE REPORT: We present a rare case of symptomatic multicentric glioma in the brain, fourth ventricle, cervical as well as lumbar glioblastoma in an adult without previous therapeutic intervention. We also review the literature of this rare presentation. CONCLUSIONS: This report suggests that GBM is a diffuse disease; the more extended the disease, the worse prognosis it has. The management still remains controversial and further studies are required to understand the prognosis factors of dissemination.

Prognostic factors and survival study in high-grade glioma in the elderly.

Background Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour in adults. Due to the ageing of the population, diagnosis in the elderly is becoming more common. The aim of this study was to analyse different combinations of treatments and to identify preoperative factors, including O6-methylguanine-DNA methyltransferase status, that may be associated with decreased survival among patients older than 70 years. Methods and materials We retrospectively included all patients over 70 years of age, who underwent surgery at the Department of Neurosurgery (HUCA and HUMV) and were diagnosed of GBM by pathological criteria from January 2007 to September 2014. Results Eighty-one patients were analysed, whose mean age was 75 (SD 4) and 48 were male. Karnofsky performance status (KPS) was over 70 in 61 patients and 38.3% presented with motor deficit. Sixty-three patients underwent resection, and 18 had only a diagnostic biopsy. The complication rate was 17.28% and mortality rate was 7.4%. Survival was increased in patients who received radiotherapy (n = 41) or additional chemotherapy (n = 26) (p < 0.001). KPS < 70 was an independent factor associated with low-rate survival. Patients with optimal treatment had a median survival of 8 months compared to patients with suboptimal treatment who had a median survival of 4 months (p < 0.001). Conclusions This study suggests that KPS is the most important preoperative prognostic factor. Maximal safe resection followed by radical radiotherapy and temozolomide might be the optimal treatment of choice since glioblastoma-diagnosed patients over 70 years of age showed a statistically significant survival benefit.

Surgical adverse events of deep brain stimulation in the subthalamic nucleus of patients with Parkinson's disease. The learning curve and the pitfalls.

BACKGROUND: Several surgical adverse events (SAEs) have been associated with Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's Disease (PD) patients, leading to certain confusion about the risk/benefit ratio of this technique, and giving rise to the need of more and more extensive control studies over longer periods. The aim of this article is to identify and quantify the factors associated with the most frequent AEs from STN DBS in PD-diagnosed patients. METHODS: The following variables were studied: aborted procedure, misplaced leads, intracranial haemorrhage, and seizures. This study was carried out in 233 patients diagnosed with PD, with 455 STN electrodes implanted and follow-up after 7 (8-14) years follow up. RESULTS: A total amount of 56 SAEs occurred in 49 patients (11.76 % of total procedures, 12.31 % of implanted leads, 21.03 % of patients). SAEs were: five aborted procedures, 26 misplaced leads, ten intracranial haemorrhages, and 15 seizures. Of all the SAEs, long-term effects only happened in two cases of hemiparesis caused by intracranial haemorrhage; the other SAEs were reversible and didn't leave any long-term clinical consequences (0.42 % of procedures, 0.44 % of leads, and 0.86 % of patients). CONCLUSIONS: STN DBS in PD patients is a safe surgical procedure, with good risk/benefit ratios: procedure reliability/correct lead implantation in 95.59 %, 0 mortality/implanted lead, 0.12 morbidity/implanted lead, and 0.0043 neurological sequelae/implanted lead.

Delayed leptomeningeal and subependymal seeding after multiple surgeries for supratentorial diffuse low-grade gliomas in adults.

OBJECT: Diffuse WHO Grade II glioma (diffuse low-grade glioma [DLGG]) is an infiltrative brain tumor that usually migrates along the white matter fibers. The delayed CSF dissemination of supratentorial DLGGs is an exceptional complication and is rarely described in adults. Here, the authors report outcomes in a surgical series of 9 patients with DLGGs with subsequent leptomeningeal and/or subependymal seeding (LMSS) following multiple incomplete resections. METHODS: The authors performed a retrospective review of patients who underwent surgery for histopathologically confirmed WHO Grade II gliomas between 1998 and 2012 and experienced a secondary CSF spread. Information regarding clinical features, surgical procedures, histopathological results, adjuvant treatment, and clinical outcomes was collected and analyzed. RESULTS: Nine consecutive patients were included in this study. There were 6 men and 3 women whose mean age was 35.5 years (range 22-59 years) at the time of initial symptom onset. All patients underwent surgery with the aid of intraoperative mapping, with incomplete tumor removal because of invasion of eloquent structures. The neuropathological examination diagnosed a DLGG in all cases (7 oligodendrogliomas, 1 astrocytoma, and 1 oligoastrocytoma). Five patients had a 1p19q codeletion. Because of tumor regrowth, the 9 patients underwent reoperation (2 surgeries in 6 cases and 3 surgeries in 3 cases), again with incomplete resection. There were no surgical complications. Adjuvant therapy (radiotherapy and chemotherapy) was administered in all patients because of progression to a higher grade of malignancy that was histopathologically confirmed in all tumors. The patients suddenly worsened, and the diagnosis of LMSS was made with a mean delay of 77 months (range 27-140 months) after the initial symptom onset. Six patients benefited from salvage chemotherapy while palliative care was chosen in 3 cases. The median survival in the 6 patients who underwent LMSS treatment was significantly longer than that in the 3 patients who did not receive salvage chemotherapy (p = 0.03). Indeed, all patients died, with a mean delay between the diagnosis of LMSS and death of 11 months (range 2-38 months) and with a mean delay between the initial symptom onset and death of 88 months (range 34-144 months). CONCLUSIONS: Cerebrospinal fluid dissemination of DLGG is a rare but possible event. It can occur throughout the progression of WHO Grade II oligodendrogliomas, oligoastrocytomas, and astrocytomas, regardless of 1p19q status. This complication seems to appear in patients who have undergone multiple incomplete resections. Salvage therapy can be considered in patients with good neurological status. However, LMSS is associated with a decreased overall survival. Therefore, this rare entity deserves further multicenter studies to better understand its pathophysiology and to adapt therapeutic strategies.

Calidad de vida tras el tratamiento quirúrgico del infarto maligno de la arteria cerebral media / Quality of life following surgical treatment of malignant middle cerebral artery infarction

Introducción. Son escasas las publicaciones que valoran la capacidad de adaptación a la enfermedad de pacientes con infarto maligno de la arteria cerebral media sometidos a cirugía descompresiva. El propósito del trabajo es analizar la calidad de vida final y el grado de satisfacción de pacientes y familiares. Pacientes y métodos. Analizamos 21 pacientes al año de ser intervenidos. Para evaluar la calidad de vida, empleamos la versión española del Sickness Impact Profile. Para conocer el grado de satisfacción retrospectiva, preguntamos a familiares y pacientes si, conociendo las secuelas actuales del afectado, habrían estado igualmente de acuerdo con realizar la craniectomía descompresiva. Resultados. La esfera física se percibe como más perturbada que la relativa a aspectos emocionales. No existen diferencias en la calidad de vida entre pacientes con afectación del hemisferio derecho o izquierdo. Los pacientes con mejor situación funcional refieren una mejor calidad de vida. El 81% de los pacientes se encuentra satisfecho. Conclusión. A pesar de que todos los pacientes muestran una reducción en la calidad de vida después de la craniectomía descompresiva, la mayoría parecen satisfechos con el tratamiento recibido, incluso en afectación del hemisferio dominante o aquéllos con una discapacidad moderada-grave (AU)

Introduction. Little work has been published on the capacity to adapt to the disease of patients with malignant middle cerebral artery infarction who have undergone decompressive surgery. The purpose of this study is to analyse the final quality of life and the degree of satisfaction of patients and their relatives. Patients and methods. We analysed 21 patients one year after their operation. The quality of life was evaluated using the Spanish version of the Sickness Impact Profile. In order to determine the degree of retrospective satisfaction, we asked relatives and patients whether, now that the patient’s current sequelae are known, they would have still agreed to a decompressive craniectomy. Results. The physical sphere is felt to be more disrupted than that concerning emotional aspects. There are no differences in the quality of life between patients who have the right or the left hemisphere affected. Patients with a better functional situation report a better quality of life. Altogether, 81% of patients said they were satisfied. Conclusions. Despite the fact that all the patients show a loss of quality of life after a decompressive craniectomy, most of them seem to be satisfied with the treatment they have received, even in cases in which the dominant hemisphere is compromised or in those with a moderate-severe disability (AU)

Bases patogénicas de la epileptogénesis en los cavernomas cerebrales / Pathogenetic bases of epileptogenesis in cerebral cavernomas

Introducción. Los cavernomas cerebrales son un tipo de malformación arteriovenosa que cursa clínicamente con crisis epilépticas, déficits neurológicos focales y hemorragias intraparenquimatosas. Se cree que las situaciones de hipoxia, neovascularización y algunas endoproteasas están implicadas en la fisiopatología de las crisis. Nuestro estudio pretende valorar esta posible relación, analizando con métodos inmunohistoquímicos la presencia de la subunidad 1α del factor inducible por hipoxia (HIF-1α) y la metaloproteasa de matriz 9 (MMP-9). Pacientes y métodos. Se seleccionaron 17 muestras consecutivas con diagnóstico anatomopatológico de cavernoma en un período de nueve años sobre las que se realizó una tinción inmunohistoquímica para HIF-1α y MMP-9, valorando la relación con las crisis epilépticas según el grado de captación del anticuerpo de los diferentes tejidos encontrados alrededor de las muestras de cavernoma. Resultados. En aquellos pacientes que presentaron crisis, se observó tinción inmunohistoquímica para HIF-1α en el 31% de las muestras en el endotelio vascular, el 17% en el tejido fibroso y el 34% en el tejido inflamatorio. También se observó tinción positiva para MMP-9 en el 86% del endotelio vascular, el 100% del tejido fibroso y el 43% del tejido cerebral. Analizando la muestra, se observa una tendencia positiva en presencia de crisis epilépticas en los pacientes que muestran la presencia de HIF-1α y MMP-9 en el endotelio vascular, tejido fibroso y tejido cerebral, no siendo así para el tejido inflamatorio. Conclusión. La expresión de HIF-1α y MMP-9, evaluada por métodos inmunohistoquímicos, se relaciona positivamente con la presencia de complicaciones de tipo epiléptico (AU)

Introduction. Brain cavernoma are a type of arteriovenous malformation that clinically presenting seizures, neurological deficit or bleeding. Hypoxia, neoangiogenesis and metalloproteasas seems to be involved in seizures physiopathology. Our study aims to assess this potential relation by immunohistochemical methods, analyzing hypoxia inducible factor (HIF-1alpha) and metalloproteasa (MMP-9) in tissue surrounding cavernoma. Patients and methods. We selected 17 consecutive cases anatomopathologically diagnosed as cavernoma during 9 years. Immunohistochemical staining was performed for HIF-1alpha and MMP-9. We evaluated the relation between seizures and the scale of uptake of different tissues surrounding cavernoma. Results. Cases with seizures had HIF-1alpha positive uptake in vascular endothelium in 31%, 17% in fibrous tissue and 34% in inflammatory tissue. Besides, it also shows MMP-9 positive uptake in vascular endothelium in 86%, 100% in fibrous tissue and 43% of brain tissue. Statistical analysis by chi-square and odds ratio shows a positive trend towards seizures and the presence of HIF-1alpha and MMP-9 in vascular tissue, fibrous tissue and brain tissue, but no for inflammatory tissue. Conclusion. HIF-1alpha and MMP-9, valued by immunohistochemical methods, are related to complications as seizures (AU)

[Quality of life following surgical treatment of malignant middle cerebral artery infarction]. / Calidad de vida tras el tratamiento quirúrgico del infarto maligno de la arteria cerebral media.

INTRODUCTION: Little work has been published on the capacity to adapt to the disease of patients with malignant middle cerebral artery infarction who have undergone decompressive surgery. The purpose of this study is to analyse the final quality of life and the degree of satisfaction of patients and their relatives. PATIENTS AND METHODS: We analysed 21 patients one year after their operation. The quality of life was evaluated using the Spanish version of the Sickness Impact Profile. In order to determine the degree of retrospective satisfaction, we asked relatives and patients whether, now that the patient's current sequelae are known, they would have still agreed to a decompressive craniectomy. RESULTS: The physical sphere is felt to be more disrupted than that concerning emotional aspects. There are no differences in the quality of life between patients who have the right or the left hemisphere affected. Patients with a better functional situation report a better quality of life. Altogether, 81% of patients said they were satisfied. CONCLUSIONS: Despite the fact that all the patients show a loss of quality of life after a decompressive craniectomy, most of them seem to be satisfied with the treatment they have received, even in cases in which the dominant hemisphere is compromised or in those with a moderate-severe disability.