Outcome of cancer-related seizures in patients treated with lacosamide.

OBJECTIVES: Lacosamide is an antiepileptic drug (AED), which has proven to be effective to control seizures, including acute conditions such as status epilepticus. The aim of this study is to describe the clinical experience with lacosamide in neuro-oncological patients. MATERIALS AND METHODS: Multicenter retrospective study in patients with cancer-related seizures, who received lacosamide as an add-on therapy. RESULTS: Forty-eight patients with benign and malignant tumors, including primary brain tumors, lymphomas, systemic cancer with central nervous system involvement, or paraneoplastic encephalitis, were included. Lacosamide was effective in the control of chronic seizures in patients with either benign or malignant tumors. The success rate was greater in malignant tumors, and drug-resistant epilepsies were more likely associated with benign tumors. Adverse events occurred in nearly 70% of patients, particularly in acute conditions and associated with the concomitant use of radio-/chemotherapy. Lacosamide-related adverse events were more likely somnolence and dizziness, which usually resolved after dose adjustment. After starting lacosamide, nearly half of the patients discontinued one of the baseline AEDs and decreased or discontinued dexamethasone. Fifteen patients with status epilepticus were treated with intravenous lacosamide, and 73% of them had their condition resolved without serious drug-related adverse events. CONCLUSION: Lacosamide is an AED to consider in cases of cancer-related seizures. Lacosamide pharmacodynamics and pharmacokinetics allow the achievement of responder rates over 50% with no serious adverse effects, amelioration of side effects from other AEDs or radio-/chemotherapy, and no significant drug interactions. Furthermore, the intravenous formulation shows clear benefits in acute conditions such as status epilepticus.

Infrared pupillometry. Basic principles and their application in the non-invasive monitoring of neurocritical patients.

INTRODUCTION: Pupil assessment is a fundamental part of the neurological examination. Size and reactivity to light of each pupil should be recorded periodically since changes in these parameters may represent the only detectable sign of neurological deterioration in some patients. However, there is great intraobserver and interobserver variability in pupil examination due to the influence of many factors, such as the difference in ambient lighting, the visual acuity and experience of the examiner, the intensity of the luminous stimulus, and the method used to direct this stimulus. In recent years, digital cameras have incorporated infrared devices allowing the development of user-friendly portable devices that permit repeated, non-invasive examinations of pupil size and its reactivity to light with an objective, accessible and inexpensive method. DEVELOPMENT: The purpose of this review is to describe the fundamentals of infrared pupillometry and discuss potential applications in the monitoring of neurocritical patients. We also present some recommendations in the routine assessment of pupils in neurocritical patients. CONCLUSIONS: The possibility of evaluating the changes in pupil reactivity in an early, objective and almost continuous way provides a new non-invasive monitoring method. This method could improve the predictive factor of neurological deterioration and the bedside monitoring of the neurological state of the patient, avoiding unnecessary examinations and enabling early therapeutic intervention.

Genomic analysis of severe hypersensitivity to hygromycin B reveals linkage to vacuolar defects and new vacuolar gene functions in Saccharomyces cerevisiae.

The vacuole of Saccharomyces cerevisiae has been a seminal model for studies of lysosomal trafficking, biogenesis, and function. Several yeast mutants defective in such vacuolar events have been unable to grow at low levels of hygromycin B, an aminoglycoside antibiotic. We hypothesized that such severe hypersensitivity to hygromycin B (hhy) is linked to vacuolar defects and performed a genomic screen for the phenotype using a haploid deletion strain library of non-essential genes. Fourteen HHY genes were initially identified and were subjected to bioinformatics analyses. The uncovered hhy mutants were experimentally characterized with respect to vesicular trafficking, vacuole morphology, and growth under various stress and drug conditions. The combination of bioinformatics analyses and phenotypic characterizations implicate defects in vesicular trafficking, vacuole fusion/fission, or vacuole function in all hhy mutants. The collection was enriched for sensitivity to monensin, indicative of vacuolar trafficking defects. Additionally, all hhy mutants showed severe sensitivities to rapamycin and caffeine, suggestive of TOR kinase pathway defects. Our experimental results also establish a new role in vacuolar and vesicular functions for two genes: PAF1, encoding a RNAP II-associated protein required for expression of cell cycle-regulated genes, and TPD3, encoding the regulatory subunit of protein phosphatase 2A. Thus, our results support linkage between severe hypersensitivity to hygromycin B and vacuolar defects.

[Primary decompressive craniectomy in patients with aneurysmatic subarachnoid hemorrhage. Results of a pilot study in 11 cases]. / Craniectomía descompresiva primaria en la hemorragia subaracnoidea aneurismática. Resultados deun estudio piloto en 11 casos.

INTRODUCTION: Despite the scientific and technical advances of recent years, aneurysmal subarachnoid hemorrhage (aSAH) continues to present a high morbidity and mortality. This fact, together with the impressive results of the primary decompressive craniotomy (PDC) in the malignant infarction of the middle cerebral artery suggests a possible beneficial effect of decompressive technique in aSAH. We present our experience of a pilot study that PDC was used in patients with poorgrade aSAH with associated intracerebral hematoma. PATIENTS AND METHODS: Between March 1st, 2002 and 31st April, 2008, 342 patients with aneurysmatic subarachnoid hemorrhage (aSAH) were treated at our hospital. Of these, 64 had a poor neurological grade (scores of 4 or 5 of the World Federation of Neurosurgical Societies) at the time of admission. The present study examines 11 of those patients who underwent PDC, which is performed in the same clipping and / or evacuation of an associated hematoma. RESULTS: In three patients PDC was performed after endovascular aneurysm treatment because of the need to evacuate an associated hematoma. In the eight remaining patients, PDC was performed in the same clipping and evacuation of the associated hematoma. Outcome evaluation of these eleven patients was conducted 1 year after the operation assessed by the Glasgow Outcome Scale. Six patients survived, and four of them with good results. The PDC was effective in controlling intracranial pressure in all six surviving patients. However, two of these six patients had unfavorable outcomes. Of the five who didn't survive, one patient died from a delayed epidural-subgaleal hematoma as a complication of the decompressive technique, and the other four patients died because of refractory intracranial hypertension. CONCLUSIONS: Primary DC may be beneficial in selected subgroups of patients with poor-grade aSAH. However, there is a lack of definitive evidence to support a clear recommendation for its use.

Isolated cerebral mucormycosis associated with intravenous drug use.

We present an uncommon case of isolated basal ganglia mucormycosis in a patient without any known cause of immunosuppression, but with a history of drug injection. The patient presented a good clinical and radiological response to antifungal treatment without aggressive surgical debridement (liposomal amphotericin B combined with isavuconazole for 4 weeks followed by isavuconazole as maintenance therapy for 10 months).

Neuropsychological alterations and neuroradiological findings in patients with post-traumatic concussion: Results of a pilot study. / Alteraciones neuropsicológicas y hallazgos neurorradiológicos en pacientes con conmoción cerebral postraumática. Resultados de un estudio piloto.

INTRODUCTION: Mild traumatic brain injury (mTBI) has traditionally been considered to cause no significant brain damage since symptoms spontaneously remit after a few days. However, this idea is facing increasing scrutiny. The purpose of this study is to demonstrate the presence of early cognitive alterations in a series of patients with mTBI and to link these findings to different markers of brain damage. METHODS: We conducted a prospective study of a consecutive series of patients with mTBI who were evaluated over a 12-month period. Forty-one (3.7%) of the 1144 included patients had experienced a concussion. Patients underwent a routine clinical evaluation and a brain computed tomography (CT) scan, and were also administered a standardised test for post-concussion symptoms within the first 24hours of mTBI and also 1 to 2 weeks later. The second assessment also included a neuropsychological test battery. The results of these studies were compared to those of a control group of 28 healthy volunteers with similar characteristics. Twenty patients underwent an MRI scan. RESULTS: Verbal memory and learning were the cognitive functions most affected by mTBI. Seven out of the 20 patients with normal CT findings displayed structural alterations on MR images, which were compatible with diffuse axonal injury in 2 cases. CONCLUSIONS: Results from this pilot study suggest that early cognitive alterations and structural brain lesions affect a considerable percentage of patients with post-concussion syndrome following mTBI.

[Outcomes of surgical treatment in 100 patients with arteriovenous malformations of the brain]. / Resultados del tratamiento quirúrgico en 100 pacientes con malformaciones arteriovenosas cerebrales.

AIM: To conduct a descriptive analysis of a series of patients with arteriovenous malformations (AVM) that had been treated surgically. PATIENTS AND METHODS: Of a total of 189 adult patients with AVM evaluated consecutively in our hospital, 100 patients who had undergone surgical treatment were selected; a number of demographic, clinical and radiological aspects were then analysed, together with data concerning any associated vascular lesions, the type of surgical treatment, angiographic results and clinical outcomes. RESULTS: The mean age was 34 years (range: 15-71 years). The most common presenting symptom was intracranial haemorrhage, which occurred in 60 cases (60%). The AVM were located in the supratentorial convexity in 79% of cases, 8% were deep and 13% were situated in the cerebellum. The most frequent degree, according to the Spetzler and Martin scale, was grade III. Seventeen patients had other associated lesions and it should be noted that eight patients had aneurysms. Most of the patients (78%) underwent elective surgery and, in two cases, post-embolisation. Surgical treatment (salvage surgery) was performed in 13 patients (13%) when other therapeutic options failed and seven patients were submitted to emergency operations because of brain haemorrhages. The postoperative angiographic study showed complete removal of the AVM in 98% of cases. The clinical outcomes were as follows: 75%, good recovery; 20%, moderate incapacity; and 5%, an important degree of incapacity. CONCLUSION: Surgery is the best therapeutic option for patients with AVM, if they are selected in an appropriate manner.

[Atypical ganglioglioma with BRAF V600E mutation: a case report and review of the literature]. / Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.

INTRODUCTION: Gangliogliomas are rare tumours that affect young patients, appear predominantly in the temporal lobe and usually begin with epileptic seizures. Histologically they have a grade I of malignancy, with an anaplastic form that is catalogued as grade III in the 2007 WHO classification. Yet, there are tumours that do not meet the criteria of either grade and which offer clear prognostic differences with respect to those of grade I. These tumours would be atypical gangliogliomas (grade II), which are not considered in this classification. From the molecular point of view, the best known alteration in gangliogliomas is the BRAF V600E mutation, which worsens the prognosis of the lesion. The possible use of treatments targeted towards this mutated protein is especially relevant in this disorder. CASE REPORT: A 21-year-old male, who had undergone surgery due to a ganglioglioma on two occasions. The neuro-pathological examination revealed histological features consistent with an intermediate grade of malignancy (grade II), with positive BRAF mutation. CONCLUSIONS: The case presented here, together with those previously reported in the literature, reopens the debate on the definition of gangliogliomas in the 2007 WHO classification, and lends support to the fact that the next classification should again include atypical gangliogliomas (grade II), together with possible genetic mutations and molecular disorders.

TITLE: Ganglioglioma atipico con mutacion de BRAF V600E: caso clinico y revision de la bibliografia.Introduccion. Los gangliogliomas son tumores raros que afectan a pacientes jovenes, aparecen predominantemente en el lobulo temporal y suelen comenzar con crisis epilepticas. Histologicamente corresponden a un grado I de malignidad, con una forma anaplasica catalogada como de grado III en la clasificacion de la Organizacion Mundial de la Salud (OMS) de 2007. Sin embargo, existen tumores que no cumplen criterios de uno u otro grado y que presentan claras diferencias pronosticas respecto a los de grado I. Estos tumores corresponderian a gangliogliomas atipicos (grado II), no contemplados en la citada clasificacion. Desde el punto de vista molecular, la alteracion mas conocida en los gangliogliomas es la mutacion de BRAF V600E, que confiere peor pronostico a la lesion. La posibilidad de utilizar tratamientos dirigidos a esta proteina mutada otorga una especial relevancia a esta alteracion. Caso clinico. Varon de 21 años, intervenido de un ganglioglioma en dos ocasiones, en el que el examen neuropatologico objetivo caracteristicas histologicas compatibles con un grado de malignidad intermedio (grado II) con mutacion positiva a BRAF. Conclusiones. El caso presentado, junto con los descritos previamente en la bibliografia, reabre las controversias sobre la definicion de los gangliogliomas en la clasificacion de la OMS de 2007, y apoya el hecho de que la proxima clasificacion de la OMS deberia volver a incluir los gangliogliomas atipicos (grado II) e integrar posibles mutaciones geneticas y alteraciones moleculares.