A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme.

Delta(9)-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC action on the length of survival and various tumour-cell parameters. A dose escalation regimen for THC administration was assessed. Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95% confidence interval: 15-33). Delta(9)-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.

[Cauda syndrome due to spinal stenosis and diskytis in two different spinal levels. Diagnosis using myelo-TC]. / Síndrome de cause secundario a estenosis y discitis en dos diferentes niveles raquídeos, diagnóstico por mielo-TC

We report a case of a 75 year old man presenting with paraparesis, urinary incontinence and saddle anesthesia evolving after several months and severe lumbalgia and bad general status which developed fewdays before admission. CT-scan showed spondilosis with lytic lesion at L5-S1 level. MR1 was not performed because the patient had a pacemaker. A myelo-CT study was performed showing a complete stop at L4-L5 level together with L5-S1 diskytis. Laminectomy of L5 and discectomy L5-S1 was performed obtaining tissue sample diagnostic of diskytis and osteomyelitis. Our patient had two lesions at two different levels with two independent syndromic appearence. Myelo-CT played an important diagnostic role in this case because MRI study could not be obtained.

Síndrome de cauda secundario a estenosis y discitis en dos diferentes niveles raquídeos, diagnóstico por mielo-TC / Cauda syndrome due to spinal stenosis and diskytis in two different spinal levels. Diagnosis using myelo-TC

Presentamos el caso de un paciente de 71 años de edad con clínica de paraparesia de varios meses de evolución incontinencia urinaria y anestesia en silla de montar, asociado a intensa lumbalgia y deterioro del estado general de varios días de evolución. La TC de raquis lumbosacro demuestra espondilodiscartrosis con lesión línea L5-S1. El estudio de resonancia magné-tica (RM) no pudo realizarse dado que el paciente era portador de marcapasos. La realización de mielo-TC permitió apreciar stop completo a nivel L4-L5 asociado a discitis L5-Sl. Se llevó a cabo descompresión L4-LS y discectomía LS-S1 obteniéndose una muestra compatible con discitis y osteomielitis. El presente caso tiene la originalidad de asociar dos lesiones en dos niveles distintos con cuadros clínicos independientes. Por otro lado la dificultad asociada de no poder realizar RM hizo de la mielo-TC un arma diagnóstica de gran utilidad (AU)

[Fibrinolytic treatment of cerebral intraventricular hemorrhage]. / Tratamiento fibrinolítico de la hemorragia intraventricular cerebral.

INTRODUCTION: Spontaneous cerebral intraventricular hemorrhage (SCIVH) is associated with hydrocephaly which requires ventricular drainage as treatment. Maintenance of adequate debit through the drainage system contributes to reduce morbid mortality. When the drain becomes obstructed, intermittent irrigation is necessary. This causes increased intracranial pressure and risk of infection. We propose the use of recombinant plasminogen tissue activator (r-tPA) in the treatment of SCIVH and associated hydrocephaly. CLINICAL CASES: We gave two patients with SCIVH 4 cc/day of r-tPA intraventricularly, at a concentration of 1 mg/ml over 4 consecutive days. Daily computerized tomography (CT) series were done. In both cases there was complete resolution of the SCIVH, with no complications related to the treatment. The ventricular drainage systems maintained a constant debit, did not become obstructed and required no revision. The patients did not subsequently require permanent ventricular shunts. One patient died of an unrelated septic condition. The other patient, a year later, could walk unaided, had motor dysphasia and on CT had neither intraventricular blood nor hydrocephaly. CONCLUSIONS: The intraventricular administration of r-tPA is a valid therapeutic tool in selected cases. It contributes to lysis of the intraventricular clot, permits permeability of the drainage, and may reduce the incidence of chronic hydrocephaly requiring a permanent ventricular shunt.

Symptomatic cavernous hemangioma of the occipital condyle treated with methacrylate embolization.

BACKGROUND: Cavernous hemangiomas of the cranial base are rare tumors. No case of symptomatic intraosseous angioma affecting the occipital condyle has been reported. This particular case was treated with surgical embolization using acrylic resin. CASE DESCRIPTION: A 20-year-old man with a 1-year history of neck pain and torticollis was referred to our hospital. Neuroradiological examination revealed the typical picture of an intraosseous cavernous hemangioma located in the right occipital condyle. The patient was operated through a suboccipital approach. Biopsy and direct embolization with methacrylate was performed. The definitive pathological diagnosis confirms the neuro-radiological suspicion of intraosseous cavernous hemangioma. The follow-up of the patient (4 years) revealed no recurrence of pain or abnormal posture. CONCLUSIONS: A rare case of cranial base cavernous hemangioma is reported. Methacrylate embolization can be a good option for the treatment of this uncommon lesion.

Nitric oxide synthase expression in the cerebral cortex of patients with epilepsy.

PURPOSE: Nitric oxide (NO), a short-lived radical synthesized from L-arginine by activation of the enzyme nitric oxide synthase (NOS), has been implicated in the pathophysiology of epilepsy by some investigators. However, the current data about NO and NOS in epilepsy are controversial and are derived only from animal models of epilepsy. In this study we investigated possible changes in NOS expression in the cerebral cortex of patients with epilepsy. METHODS: Qualitative and quantitative parameters of the immunolabeling pattern of the neuronal, endothelial, and inducible isoforms of NOS were analyzed in biopsy material obtained from patients with short and long seizure history and from patients without epilepsy. RESULTS: The comparative study showed that in the cerebral cortex of patients with epilepsy, particularly in those with a long seizure history, the number and labeling intensity of NOS-positive neurons increased, and that a subpopulation of nonpyramidal GABAergic neurons (type II NOS neurons) was responsible for this phenomenon. CONCLUSIONS: The fact that NOS upregulation is more evident in patients with a long seizure history suggests that this is a consequence of seizures, acting probably as an adaptative response to the sustained release of excitatory amino acids.

Depth electroencephalography in selection of refractory epilepsy for surgery. Our experience with the suboccipital approach.

Despite new diagnostic tools, the precise localisation of an epileptic focal discharge remains an important step in the surgical treatment of epilepsy. Conventional EEG not always gives enough information to decide about surgery and more invasive methods have to be used. Epidural, subdural, and intra-parenchymatous electrodes have been used to come closer to the epileptic foci. Superficial hemispheric foci are well recorded by conventional epidural or subdural, strip or grid electrodes. Deeper foci, located in the medial temporal lobe or limbic areas are much more difficult to access from surface electrodes and other methods have to be used. Stereotactic placed multielectrodes and foramen ovale electrodes are most commonly implanted. Since 1986 we have used multi-contact cylindrical soft subdural electrodes. At the beginning we made the electrodes in our Department. Later on they were commercially available. In our Clinic the electrodes are usually introduced via a suboccipital approach and directed to the medial aspects of the temporal lobes until the temporal poles on both sides. Usually a median electrode located in the interhemispheric fissure, and covering gyrus cinguli is also placed. Out of 60 procedures done for different kinds of epilepsy, including cases with tumour or other surgical epileptogenic lesions, a total of 14 patients with genuine temporal lobe epilepsy have been studied and operated by this method. The advantages of the method as compared to stereotactic intraparenchymatous implanted electrodes are: less risk of bleeding and the fact that the brain tissue in those sensitive areas remains intact. Compared to foramen ovale electrodes our technique covers larger area of the temporal lobes and allows to insert a medial limbic electrode, but demands 2 burr holes. A further advantage of our technique is that the electrodes remain in place until surgery, allowing for their use as anatomical landmarks for tailoring the extension of the resection. This approach has been found to be simple, safe and reliable. A further improvement may be the simultaneous use of PEG epidural electrodes to obtain an overall view of the electrical activity of the brain including surface, deep temporal and midline cortical areas.

Sub-occipital approach for implantation of recording multi-electrodes over the medial surface of the temporal lobe.

Recording the electrical activity from the medial aspects of the temporal lobe, including uncus and hippocampal convolution, has an important role in the preoperative evaluation of patients with drug-resistant temporal lobe epilepsy. We report our experience with subdural cylindrical multi-electrodes placed along the medial, basal and lateral aspects of the temporal lobe through a suboccipital approach. Eight patients have been examined with this technique for 3 to 8 days. The quality of the recordings was excellent. No displacement of the electrodes has been noticed. One patient developed meningitis which was successfully treated. The electrodes have been kept in place until surgery and have served as useful landmarks for the resection enabling also neurophysiological monitoring throughout the operation.

Semantic capabilities of the left and right cerebral hemispheres in categorization tasks: effects of verbal-pictorial presentation.

Two lateral tachistoscopic experiments were carried out to test semantic capabilities of the left and right cerebral hemispheres through categorization tasks with verbal and pictorial presentations. RVF advantages were obtained for verbal presentations in both category-membership and category-matching tasks. However, no significant visual-field differences were found for any pictorial presentation. We also found a higher degree of sensitiveness of the positive judgements for the detection of hemispheric differences and sex differences in patterns of functional asymmetries with a greater lateralization in males.

Design of an intracranial electrode for monitoring.

Direct recording of the electric brain activity gives more information than conventional electroencephalogram. Several authors have designed a variety of electrodes in order to solve the different problems of electrocorticography but in our opinion none of these fulfil the following features: easy implantation and extraction with minimal trauma; flexibility to allow placement over regions of the brain cortex that are difficult to access (interhemispheric fissure, medial aspect of the temporal lobe, frontobasal region, etc.), good quality recording. A multiple contact electrode which we think matches these features has been designed. Initially this electrode was tested in the postoperative monitoring of ten patients with supratentorial malignant tumours and in one case of intractable epilepsy. In two patients complications of treatment were detected, one had an epileptic seizure and the other had bleeding in the tumoural bed. In the first case a right temporal focus was delineated and posteriorly excised. Implantation of the electrode was always very simple, either from the craniotomy or from a burr hole, and its flexibility allowed us to place it over the regions above mentioned. Also the extraction was easy with a simple traction and without the need for a second intervention. In all cases the recording quality was excellent.

The effect of surgical immobilization after laminectomy in the treatment of advanced cases of cervical spondylotic myelopathy.

Surgical immobilization of the cervical spine after laminectomy is proposed for the treatment of severe cervical spondylotic myelopathy (CSM) occurring with diffuse stenosis of the spinal canal (congenital or acquired). In 20 consecutive patients showing advanced CSM and cord compression at various levels, a laminectomy with posterior fixation was made, in most cases with the aid of a metal plate. In the evaluation of the severity of the myelopathy a slight modification of the Nurick scale was used. With the exception of three patients who developed complications unrelated to the technique, the results were very good as demonstrated by the long lasting improvement in the performance of the patients. The results emphasize the role which mechanical factors may play both, in the genesis of the disease and in the failures of the plain laminectomy.

Cervical spondylotic myelopathy: a cooperative study.

A series of 521 cases of CSM in 22 clinics in Spain and Portugal were studied. The severity of the clinical picture, both before and after the operations, was graded following a six point scale (a modification of Nurick's). The operations the patients underwent were classified into eight types and their results expressed by using the same scale. Some improvement has been attained in all grades of myelopathy with all types of operations, but better results, especially in advanced cases, have been obtained when surgical fixation of the spine, as well as laminectomy, has been carried out.