Glycemia and coagulation in patients with glioblastomas.

Glioblastomas are among the most malignant tumors which, despite aggressive treatment, currently have an abysmal prognosis. These lesions are known to cause local and systemic perturbations in the coagulation system, leading to neo-angiogenesis and a high risk of venous thromboembolism. Indeed, there have been multiple proposals of the coagulation system being a possible target for future treatment of these patients. However, non-selective anticoagulant therapy has proven suboptimal and leads to a significant increase of intracranial hemorrhage. Thus, recognizing factors which lead to hyper-coagulation is considered paramount. Hyperglycemia is a well-known pro-thrombotic factor, a fact which has received little attention in neuro-oncology so-far. We previously hypothesized that patients with brain tumors could be highly susceptible to iatrogenic glycemia dysregulation. Here, we analyzed the connection between glycated hemoglobin (HbA1c) and the routine coagulation markers (D-dimers, prothrombin time (PT) and activated partial thromboplastin time (aPTT)) in patients with de novo intracranial glioblastomas. Included in this study were 74 patients, operated on in three hospitals, Clinical Hospital Dubrava, Zagreb, Croatia; University Hospital Center Split, Split, Croatia and University Hospital de la Princesa, Madrid, Spain. We found a significant inverse correlation between HbA1c and aPTT (ρ=-0.379; P=0.0009). We also found a significant inverse correlation between Ki67 immunoreactivity and aPTT (ρ=-0.211; P=0.0082). No connection was found between HbA1c and D-dimers or PT. Our results suggest that hyperglycemic patients, with a more proliferative glioblastoma, could in fact have their coagulation profile significantly disrupted, primarily through the intrinsic coagulation pathway. Such findings could have great clinical importance. Further research in this area could help elucidate the vicious connection between glioblastomas and coagulation, and help combat the deadly disease.

Chronic hyperglycemia and intracranial meningiomas.

Meningiomas are among the most common primary tumors of the central nervous system. Previous research into the meningioma histological appearance, genetic markers, transcriptome and epigenetic landscape has revealed that benign meningiomas significantly differ in their glucose metabolism compared to aggressive lesions. However, a correlation between the systemic glucose metabolism and the metabolism of the tumor hasn't yet been found. We hypothesized that chronic levels of glycaemia (approximated with glycated hemoglobin (HbA1c)) are different in patients with aggressive and benign meningiomas. The study encompassed 71 patients with de novo intracranial meningiomas, operated on in three European hospitals, two in Croatia and one in Spain. Our results show that patients with WHO grade 2 meningiomas had significantly higher HbA1c values compared to patients with grade 1 lesions (P = 0.0290). We also found a significant number of patients (19/71; 26.7%) being hyperglycemic, harboring all the risks that such a condition entails. Finally, we found a significant correlation between our patients' age and their preoperative HbA1c levels (P = 0.0008, ρ(rho) = 0.388), suggesting that older meningioma patients are at a higher risk of having their glycaemia severely dysregulated. These findings are especially important considering the current routine and wide-spread use of corticosteroids as anti-edematous treatment. Further research in this area could lead to better understanding of meningiomas and have immediate clinical impact.

[Surgical treatment for spontaneous intracerebral haemorrhage. Part II: infratentorial haematomas]. / Tratamiento quirúrgico de la hemorragia intracerebral espontánea. Parte II:Hemorragia infratentorial.

Surgery plays a mayor role in the management of some patients with cerebellar haematomas, although a universally accepted treatment guideline is lacking. The aim of this study was to review the existing evidence supporting surgical evacuation of the haematoma in this pathology. Without any clinical trial on this field, data derived from clinical series suggest that the level of consciousness, the size of the haematoma, the presence of hydrocephalus and the compression of the posterior fossa CSF containing spaces are the main criteria to decide management. Fourth ventricular compression seems to be the best indicator of the last parameter. Existing bibliography shows that haematomas greater than 4 cm or causing complete obliteration of the fourth ventricle or prepontine cistern need surgical evacuation irrespective of the level of consciousness, as they indicate a significant compression of the brainstem. On the other hand, it seems that haematomas of less than 3 cm and without fourth ventricular compression can be managed conservatively or by means of ventricular drainage if hydrocephalus exists and requires treatment. The management of intermediate sized haematomas is less clear although conservative approach could be adopted in presence of adequate neurological status, with EVD in the case of hydrocephalus with low consciousness level. If the level of consciousness is low despite the treatment of hydrocephalus, or in absence of this latter, haematoma evacuation is indicated. Finally, patients with flaccid tetraplejia and absent oculocephalic reflexes, and those whose age or basal condition precludes an adequate functional outcome are not suitable for aggressive treatment. Moreover, some studies have shown that comatose patients with CT scan evidence of severe brainstem compression present a reduced probability of good outcome. Anyway, management should be decided on an individual basis, as there is no enough evidence to support a strict treatment protocol.

[Value of serial CT scanning and intracranial pressure monitoring for detecting new intracranial mass effect in severe head injury patients showing lesions type I-II in the initial CT scan]. / Utilidad de la TAC secuencial y la monitorización de la presión intracraneal para detectar nuevo efecto masa intracraneal en pacientes con traumatismo craneal grave y lesión inicial Tipo I-II.

OBJECTIVE: To determine the incidence of pathological and intracranial pressure (ICP) changes during the acute posttraumatic period in severe head injury patients presenting with lesions Types I-II (TCDB classification) in the admission CT scan with the aim of defining the most appropriate strategy of sequential CT scanning and ICP monitoring for detecting new intra-cranial mass effect and improving the final outcome. MATERIAL AND METHODS: 56 patients (ages 15-80 years) consecutively admitted during a 2 years period were included. All had the initial CT scan < 24 hours after injury (mean interval = 150 min), several CT controls within the first days of the course and ICP monitoring after admission. Different epidemiological, clinical and radiological variables were recorded and deterioration defined as the development of sustained ICP over 20 mmHg requiring aggressive medical and/or surgical treatment was considered the dependent variable. Uni and multivariate analyses were made for determining the correlation between different parameters and the occurrence of deterioration and the final outcome as assessed with the GOS. RESULTS: The mean GCS score was 5 and 37% of the patients showed pupillary changes; 52.3% had peritraumatic hypotension-hypoxemia, 16.1% anemia and 12.3% coagulation changes. 50% of the patients showed petechial hemorrhages in the white matter or the brainstem, 66% SAH, 40% HIV, 39.3% brain contusion and 21.4% small extraaxial hematomas. 57.1% of the patients showed CT changes through the acute post-traumatic period consisting of new contusion (26.8% of the cases), growing of previous contusion (68.2%) or previous extraaxial hematoma (10.7%), and generalized brain swelling (10.7%). 64.9% of the patients made a favourable and 35.7% an unfavourable outcome. Overall, 27 (48.9%) patients developed deterioration, 21 (37.5%) with concurrent CT changes and 6 (10.7%) without new pathology as seen by the CT control. The remaining 29 (51.7%) patients in this series did not develop deterioration in spite that 11(19.6%) showed CT changes. The age, the initial score, the occurrence of peritraumatic hypotension-hypoxemia and coagulation disorders did not correlate with the risk of deterioration. By contrast, the presence of contusion at the initial CT scan (p= 0.01) and the occurrence of CT change (only generalized brain swelling, p= 0.003) significantly correlated with the risk of deterioration; in his turn deterioration increased by a factor of 10 (OR = 9.8) the risk of death and 7 out of the 8 patients who died developed intractable intracranial hypertension. The 8 (14.2%) patients requiring surgery showed simultaneous ICP deterioration and CT changes, but another 11 patients in a similar condition could be managed without surgery. With or without ICP deterioration, patients showing CT changes had a worse outcome than those without new pathologies, but the difference did not reach statistical significance, DISCUSSION AND CONCLUSIONS: Over 50% of the patients with initial Type I-II lesions developed new CT changes and nearly 50% showed intracranial hypertension during the acute posttraumatic period. Considering the high incidences of ICP and CT deterioration through the course, along with the absence of strong predictors and the discordances between CT and ICP changes (which were seen in 30.3% of the cases) we recommend ICP monitoring after admission in all patients and serial CT scanning at 2-4, 12, 24, 48 and 72 hours after injury with additional controls as indicated by clinical or ICP changes in all cases. Though it is clear that the presence of severe intra-cranial hypertension significantly increased the risk of death, the small size of the sample in this series prevented to assess to what extent the occurrence of new mass effect and/or raised ICP contributed to the development of moderate and severe disability in the survivors which were mainly due to the occurrence of diffuse axonal injury. Finally, demonstrating that sequential CT scanning and ICP monitoring improve the final outcome in this type of patients would require a prospective randomized trial which is impracticable for different reasons, among them the ethical ones.

Cerebellar hematoma following transsphenoidal surgery.

Cerebellar hemorrhage after supratentorial surgery is a very infrequent complication. Most cases occur following aneurysm or brain tumor surgery, or evacuation of extracerebral collections. The underlying mechanism of formation of these hematomas is unclear. We present an example of cerebellar hemorrhage following transsphenoidal resection of a pituitary adenoma. To our knowledge, this is the first case reported of hemorrhage in the posterior fossa after a transsphenoidal approach.

Oligodendroglioma and multiple sclerosis. A case report.

BACKGROUND: The concurrence of multiple sclerosis (MS) and glioma is uncommon. Approximately 30 cases have been reported, but in only six of them the tumour was pure or mixed oligodendroglioma. The appearance of new neurological symptoms and signs in a patient with multiple sclerosis is usually attributed to a relapse of this disease and neuroradiological studies are not always performed. When done, the finding of a new focal mass lesion is usually interpreted as a pseudotumoural plaque. CASE REPORT: A 37-year-old man was admitted because of partial simple seizures and an enlarging intracranial mass. He had been diagnosed of MS eleven years earlier. A MRI study performed eight years before admission showed a large mass in the right frontal lobe which was thought to be a pseudotumoural plaque. Two years later, he developed simple partial motor seizures that were initially controlled with valproic acid. He remained well until three months before admission, when seizures reappeared with a poor response to valproic acid. A new MRI study showed an heterogeneous right frontal enlarging mass lesion. A primary neoplasm was suspected and a subtotal removal was performed. The pathological diagnosis was oligodendroglioma with a periferic demyelinating area. CONCLUSION: Atypical MRI lesions in a patient with MS must be carefully interpreted. Pseudotumoural plaques have been described both clinically and radiologically to be hardly distinguishable from a tumoural lesion and histological confirmation is often required. The association between MS and glioma is uncommon but it must be kept in mind when a mass lesion develops in a patient with MS.

Meningiomas of the basal posterior fossa. Surgical experience in 80 cases.

INTRODUCTION: Despite recent improvements in microsurgical and radiotherapy techniques, treatment of basal posterior fossa meningiomas still carries an elevated risk of morbidity. We present our results in a series of patients with this type of tumor and review the recent literature looking for the results obtained with different approaches and the new tendencies and algorithms proposed for managing these challenging lesions. MATERIAL AND METHODS: We analyzed retrospectively the clinical presentation and outcome of 80 patients consecutively operated between 1979 and 2003 for basal posterior fossa meningioma (foramen magnum tumors excluded). All patients had preoperative CT scans and the majority MRI studies. A total of 114 operations were performed including two-stage operations, reoperation for recurrence, CSF diversion, and XII-VII anastomosis. The most commonly used approaches were lateral suboccipital retrosigmoid, subtemporal-transtentorial, frontotemporal pterional and supra-infratentorial presigmoid. Thirteen patients received postoperative radiotherapy. RESULTS: There were 59 (73.7%) women and 21 men (mean age = 51.5 years; range = 18-78 yrs). Most common presenting symptoms were cranial nerve dysfunction, gait disturbances and intracranial hypertension. The mean duration of symptoms was 2.9 years. 70% of the tumors were over 3 cm in size. Fifty patients (62.5%) had a complete resection, 22 (27.5%) subtotal resection (> 90% tumor volume removed), and 8 (10%) only partial resection. Postoperative complications included hematoma, CSF leak, and infection. Fifty four (67.5%) patients developed new or increased cranial nerve deficits and 12.5% somatomotor, somatosensory or cerebellar deficits immediately after surgery with subsequent improvement in most cases. Following initial surgery 67 patients made a good recovery, 10 developed variable degrees of disability and 3 died. Eleven patients died later in the course for tumor recurrence with or without reoperation, malignant meningioma or unrelated causes. There were 9 recurrences in the subgroup of patients having complete resection initially (mean follow-up = 8.6 years). The majority of patients having initial subtotal or partial resections have been managed without reoperation during a mean follow-up period of 6.5 years (radiosurgery and/or observation). DISCUSSION AND CONCLUSION: Current microsurgical and radiotherapy techniques allow either a cure or an acceptable control of basal posterior fossa meningiomas. In patients with tumor invasion of the cavernous sinus, extracranial extension, violation of the arachnoidal membranes in front of the brainstem, or encasement and infiltration of major arteries, a subtotal excision seems preferable followed by observation and/ or radiosurgical treatment. Apart from the patients age and the clinical presentation (symptomatic or not), the size and secondary extensions of the tumor must be taken into account for planning treatment in the individual patient.

[Arteriovenous malformation of the middle and posterior third section of the corpus callosum treated with embolization and surgery]. / Malformación arteriovenosa de los tercios medio y posterior del cuerpo calloso tratada con embolización y cirugía.

We are presenting the case of a 58 year-old woman with an arteriovenous malformation (AVM) of the middle and posterior thirds of the corpus callosum which had produced two episodes of bleeding before admission to our Department, when the patient was neurologically intact. The nidus was fed by the anterior and posterior pericallosal arteries draining through the left medial atrial vein to the vein of Galen, by parasagittal cortical veins to the superior sagittal sinus and by right temporal veins to the sphenoparietal sinus. The patient underwent embolization of the anterior and posterior feeders in two sessions separated by a week interval, and then the AVM was removed through a left paramedial parietooccipital craniotomy in a single stage. The patient showed transient mild short term memory deficit, but the final outcome was excellent.

Surgical treatment of trigonocephalies and associated hypoteleorbitism.

Premature closure of metopic suture is a relatively uncommon form of craniosyostosis with an estimated incidence of 0,3 per 1000 live births, comprising about 7% of surgical craniosynostosis referred to craniofacial centers. A broad phenotypical spectrum spreads from minor metopic ridges to severe trigonocephaly with pterional indentation supraorbital bar retrusion, temporal and parietal compensating bossings and hypotelorism. Most of the cases arise spontaneously although autosomal dominant inheritance has been described and association with cromosomal abnormalities and different syndromes has been widely reported. Surgical correction has been attempted with good cosmetic results using several variations of the standard frontoorbitary advance. However there is still a number of questions to be solved in relation to this entity, mainly on its pathogenesis, but also on its development, natural history and treatment. Direct surgical approach to associated hypotelorism is a matter of argument when considering the reestablishment of normal interorbitary distances. We have conducted a retrospective analysis of our serie consisting of twenty-eight cases of trigonocephalies. Surgical correction of hypotelorism was attempted in eleven cases while the resting seven children remained "not treated". The objective was to review the functional outcome and cosmetic results comparing the different techniques applied to the frontal bone and to observe evolution of the hypoteleorbitism after the treatment with or without osteotomies and grafting of the nasoethmoidal area.

Intratumoural bleomycin as a treatment for recurrent cystic craniopharyngioma. Case report and review of the literature.

INTRODUCTION: The majority of craniopharyngioma (CF) have a cystic component and only 10% are completely solid. In tumors with a large cystic component, stereotactic drainage or instillation of radioctive and/or chemotherapeutic agents have been used. Only several authors have reported the use of bleomycin for the treatment of cystic CF. CASE REPORT: The authors present the case of a nineteen years old patient with a recurrent cystic CF who was treated with intratumoral injections of bleomycin. The patient had been operated on three times before because of regrowth of the tumor. This last time he had a severe disturbance of his visual acuity and a huge regrowth of the cystic CF. An intracystic catheter stereotactically placed was connected to an Ommaya reservoir and, after assuring the impermeability of the cyst, bleomycin was administered through the reservoir up to a total dose of 45mg distributed in six doses. No complications were detected during and after the procedure. A MR performed 4 months after treatment showed a clear reduction in the size of the cyst but 10 months later a new regrowth of the cyst was detected by MR with no new signs or symptoms. A total dose of 30 mg divided in six doses was administered. No complications occurred. The MR 18 months after the first treatment showed the reduction in size of the tumor. The ophtalmological study showed almost normal visual acuity in both eyes. DISCUSSION: Although there is not an stablished protocol for the indication and the form of application of intracystic bleomycin, results with this treatment for cystic CF seem good in the literature. However, the risk of local complications after the administration of intratumoural bleomycin in these patients is around 10%, and some fatal toxic reactions have been recently reported. CONCLUSION: Intracystic administration of bleomycin is a valid option as adjuvant therapy for CF in patients with recurrences that are not surgical candidates because of the high risk of complications. The role of bleomycin as a primary treatment for CF and treatment protocols remain to be stablished with additional studies.

[Meningioma of the olfactory groove: review of a series of 27 cases]. / Meningiomas del surco olfatorio: revisión de una serie de 27 casos.

OBJECTIVE: To describe our experience with olfactory groove meningiomas, analysing their clinical and radiological form of presentation and their surgical treatment. METHODS: The clinical records of 27 patients diagnosed of olfactory groove meningioma, extracted from the series of meningiomas operated on in our department since 1973, were retrospectively reviewed. Demographical data, the clinical presentation and duration of the symptoms before diagnosis were collected. Several radiological characteristics were also reviewed such as the tumour size, associated brain edema, type of contrast enhancement, presence of endostosis and invasion of the cranial base. The surgical resection grade, the histological type and the presence of recurrences in the follow-up were also analysed. RESULTS: The average age at presentation was 59 years. Average duration of symptoms prior to diagnosis was 39 months. The most frequent symptom at presentation was higher function impairment (52%), The average maximum tumoral diameter was 6.2 cm. 61% of the patients presented moderate or severe brain edema, which was quite frequently bilateral (74%). Radiological endostosis was present in 37% of the cases, but there were no signs of bone invasion in any case. The approach used was the basal frontal, uni or bilateral. In all cases the grade of resection was Simpson II. The majority of the cases presented a typical histology. Over 80% of the cases presented a good recovery at discharge. None of the patients presented with a tumoral recurrence after an average radiological follow-up of 74 months. CONCLUSIONS: The olfactory groove is an infrequent location for intracranial meningiomas, accounting for only 4.5% of all meningiomas in our experience. These tumours reach a big size due to the delay in diagnosis. Drilling of the cranial base does not seem necessary for preventing tumoral recurrence.

[Tentorial meningiomas. A study of 14 surgically verified cases]. / Meningiomas del tentorio: análisis de 14 casos operados.

OBJECTIVE: Complete surgical resection is considered to be the elective treatment for tentorial meningiomas. The objective of this work is to describe the clinical and radiological characteristics of these tumours, the best surgical approach, complications related to surgery and long term outcome of patients harbouring a meningioma at this location. MATERIALS AND METHODS: A series of 14 patients with tentorial meningiomas consecutively operated at our department between 1977 and 1999 is analyzed. Twelve patients were studied with CT and the last 8 with MR. Arteriography or angio-MR were performed in some patients when dural sinuses involvement was suspected. Tumoral resection was evaluated by means of Simpson Scale and final outcome according to the Glasgow Outcome Scale (GOS). RESULTS: Nine patients were female and 5 male. Mean age was 64 years (41-82). The average duration of presenting symptoms was 17 months. Headache was the most frequent presenting symptom. The tumour was implanted at the tentorial free edge in 4 cases, at the lateral region in 9 and at the falcotentorial region in 1 case. Complete surgical resection (Simpson I-II) was achieved in 10 cases. Final outcome was good recovery in 9 cases, moderate disability in 1, severe disability in 2 and two patients died. CONCLUSIONS: Surgery is the elective treatment for tentorial meningiomas. In most cases, complete surgical resection should be the objective. Subtotal resection may be considered when the tumour invades a patent dural sinus or the cavernous sinus or when the tumour is closely adherent to the brain stem. In these cases a close follow up is needed and reoperation or radiosurgical treatment may be contemplated if residual tumour growth occurs.

Intracranial hemangiopericytoma: study of 12 cases.

Most hemangiopericytomas (HPCs) are located in the musculoskeletal system and the skin, while the intracranial location is rare. They represent 2 to 4% in large series of meningeal tumours, thus accounting for less than 1% of all intracranial tumours. Many authors have argued about the true origin of this tumour. The current World Health Organization classification of Central Nervous System tumours distinguishes HPC as an entity of its own, and classified it into the group of "mesenchymal, non-meningothelial tumours". Radical surgery is the treatment of choice, but must be completed with postoperative radiotherapy, which has proved to be the therapy most strongly related to the final prognosis. HPCs have a relentless tendency for local recurrence and metastases outside the central nervous system which can appear even many years after diagnosis and adequate treatment of the primary tumour. Twelve patients with intracranial HPC were treated at our Unit between 1978 and 1999. There were 10 women and 2 men. Ten tumours were supratentorial and most located at frontoparietal parasagittal level. The most common manner of presentation was a focal motor deficit. All tumours were hyperdense in the basal Computed Tomography scans and most enhanced homogeneously following intravenous contrast injection. In 50% of cases, tumour margins were irregular or lobulated. Seven tumours were studied with Magnetic Resonance Imaging, being six of them iso-intense with the cortical gray matter on T1-weighted and T2-weighted images. Twenty operations were performed in the 12 patients. In 10 cases radical excision could be achieved with no operative mortality. Total recurrence rate was 33.3%. Eight patients were treated with external radiotherapy at some time through the course of their disease. Eight out of the 12 patients in this series are disease-free (Glasgow Outcome Scale categories 1 and 2) after a mean follow up of 52 months.

Parosteal osteosarcoma of the skull.

Parosteal osteosarcoma of the skull is a distinct surface bone tumor, with a better prognosis than conventional osteosarcoma. The most common location is on the surface of the distal femur which accounts for 46-66% of the cases. The presentation in the skull is uncommon and there are few cases reported in the literature. We describe the case of a man who developed a parosteal osteosarcoma arising from the occipital bone with extension to the parietal bone. The patient was operated and had a complete tumor resection.