DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

Updating old ideas and recent advances regarding the Interstitial Cells of Cajal.

Since their discovery by Cajal in 1889, the Interstitial Cells of Cajal (ICC) have generated much controversy in the scientific community. Indeed, the nervous, muscle or fibroblastic nature of the ICC has remained under debate for more than a century, as has their possible physiological function. Cajal and his colleagues considered them to be neurons, while contemporary histologists like Kölliker and Dogiel categorized these cells as fibroblasts. More recently, the role of ICC in the origin of slow-wave peristaltism has been elucidated, and several studies have shown that they participate in neurotransmission (intercalation theory). The fact that ICC assemble in the circular muscular layer and that they originate from cells which emerge from the ventral neural tube (VENT cells), a source of neurons, glia and ICC precursors other than the neural crest, suggests a neural origin for this particular subset of ICC. The discovery that ICC express the Kit protein, a type III tyrosine kinase receptor encoded by the proto-oncogene c-kit, has helped better understand their physiological role and implication in pathological conditions. Gleevec, a novel molecule designed to inhibit the mutant activated version of c-Kit receptors, is the drug of choice to treat the so-called gastrointestinal stromal tumours (GIST), the most common non-epithelial neoplasm of the gastrointestinal tract. Here we review Cajal's original contributions with the aid of unique images taken from Cajal's histological slides (preserved at the Cajal Museum, Cajal Institute, CSIC). In addition, we present a historical review of the concepts associated with this particular cell type, emphasizing current data that has advanced our understanding of the role these intriguing cells fulfil.

[Intraoperative neurophysiological monitoring of the spinal cord: our experience]. / Monitorización neurofisiológica intraoperatoria de la médula espinal: nuestra experiencia.

INTRODUCTION: The main objective of intraoperative monitoring of the spinal cord is to detect any neurological damage that may occur (and which would otherwise go unnoticed) while it is still reversible. AIM: To retrospectively evaluate the effectiveness of neurophysiological monitoring in spine and spinal cord surgery since the time such procedures were first implemented within our centre. PATIENTS AND METHODS: The patients were divided into three groups, according to their pathologies. They were clinically evaluated with the McCormick scale before surgery, on discharge from hospital and at six months after the operation. Neurophysiological monitoring was performed with motor evoked potentials, somatosensory potentials and screw stimulation, when appropriate. RESULTS: The sample finally consisted of 49 subjects, with a mean age of 51 +/- 19.4 years. Distribution by groups was 53.1% spinal cord tumours, 22.4% traumatic injuries to the spinal cord and 24.5% bone/disc pathologies. During surgery potentials improved in 4.08% of patients, in 63.26% they remained intact, 20.41% were alerted by the neurophysiologist with intact potentials, 10.2% suffered a transitory decline and in one case there was permanent loss. All the patients who were submitted to a follow-up at six months displayed a clinical status that was the same or better than the one before their operation. CONCLUSIONS: Neurophysiological monitoring is a valuable tool that prevented, in 30.61% of our patients, damage that could otherwise have occurred. From the clinical point of view, its high predictive value is also worth highlighting.

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.

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.