[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Glioblastoma (GBM) is the most life-threatening primary brain tumor, especially in elderly. Despite aggressive
treatment, median survival among all GBM patients is only 12-15 months and is worse in elderly (6-9 months). The standard
of care for elderly remains controversial. The purpose of this study is to assess the benefit of conventional treatment (Stupp
regimen) in elderly patients. METHOD: We retrospectively reviewed a prospective database of 209 patients who were diagnosed
with GBM at a single center from January 2005 to March 2013. All patients were divided into younger and elderly groups based
on the cut-off age of 65 years. RESULTS: Of 209 patients diagnosed with GBM, 122 (58%) patients were younger than 65 years,
and 87 (42%) patients were 65 years old or older. No differences were found in basal patient characteristics and neither in
grade of resection between age subgroups. However elderly received less active treatment, radio-chemotherapy was less frequent
in elderly (51% vs 73%) but radiotherapy alone (18% vs 8%) and non-oncological treatment after surgery was more frequent in
elderly (31% vs 18%) (p = 0.002). No differences in median survival were found in elderly patients who received the same approach
treatment than young patients. Median OS was 10.8 months in all GBM patients, 8.7 months in older and 13.6 months in younger
patients (p = 0.019). Of all, 106 (51%) patients received Stupp regimen, 41 (47%) elderly and 65 (53%) young. Median OS in
patients treated with conventional treatment was 18 months, without differences by age, 15.3 months in older and 18 months
in younger (p = 0.228), neither differences were found in PFS (global of 8.2 months, 9.7 and 8.2 months, p = 0.307). MGMT
status information was available only for 45.5% of patients that received Stupp regimen, 23 MGMT methylated, 25 MGMT unmethylated
and 58 patients with MGMT not evaluable or not done. Surprisingly, no differences in OS were found between groups by MGMT
status (19.2, 18.1 and 15.7 months respectively, p = 0.405). Significant differences in OS and post-progression survival (PPS)
were found if patients received or not treatment at relapse (7.7 versus 20 months, p < 0.0001 and 1.7 versus 8.9 months, p
< 0.0001). No differences between age subgroups in receiving it or not. Bevacizumab (BVZ) was the recurrence treatment in
60% of patients treated (31/52). PPS was better in patients treated with BVZ than in those treated with chemotherapy or surgery
(12.4, 5.1 and 8.9 months, p < 0.0001). CONCLUSION: Elderly population newly diagnosed with GBM benefit from conventional
treatment. Probably, undertreatment is the most important factor associated with poor survival in elderly newly diagnosed
with GBM. Therefore, elderly patients should be encouraged to receive conventional active treatment. Recurrence treatment
with bevacizumab might be an important factor in improving survival in the last few years.
[Show abstract][Hide abstract] ABSTRACT: Background
Bilateral regional brain oxygen saturation (rSO2) trends, reflecting intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various types of cognitive impairment, such as memory decline, alterations in executive function or subjective complaints, have been described three months after surgery. Our aim was to explore the potential utility of rSO2 values as a warning sign for the development of different types of decline in postoperative psychological function.
Observational post-hoc analysis of data for the patient sample (n = 125) of a previously conducted clinical trial in patients over the age of 65 years undergoing total knee replacement under spinal anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values were recorded. An absolute rSO2 value of <50% or a reduction of >20% or >25% below baseline were chosen as relevant cutoffs. Composite function test scores were created from baseline to three months for each patient and adjusted for the mean (SD) score changes for a control group (n = 55). Tests were used to assess visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol-Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal Learning, Wechsler Memory Scale); scales were used to assess psychological symptoms.
We observed no differences in baseline rSO2 values; rSO2 decreased significantly in all patients during surgery (P < 0.0001). Seventy-five patients (60%) had no sign of cognitive decline or psychological symptoms. Twenty-one patients (16.8%) had memory decline, 3 (2.4%) had VM-EF decline, and 33 (26.4%) had psychological symptoms. Left and right rSO2 values were asymmetric in patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs 101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower on the right, P = 0.0034).
Detection of a trend to asymmetry in rSO2 values can warn of possible postoperative onset of memory decline. Psychological symptoms and memory decline were common three months after knee replacement in our patients over the age of 65 years.
[Show abstract][Hide abstract] ABSTRACT: While there is solid experimental evidence of brain oxidative stress in animal models of epilepsy, it has not been thoroughly verified in epileptic human brain. Our purpose was to determine and to compare oxidative stress markers in the neocortex of epileptic and non-epileptic humans, with the final objective of confirming oxidative stress phenomena in human epileptic brain.
Neocortical samples from drug-resistant epilepsy patients submitted to epilepsy surgery (n=20) and from control, non-epileptic cortex samples (n=11) obtained from brain bank donors without neurological disease, were studied for oxidative stress markers: levels of reactive oxygen species (ROS), such as superoxide anion (O2(-)); activity of antioxidant enzymes: superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase (GR); and markers of damage to biomolecules (lipid peroxidation and DNA oxidation).
Compared with non-epileptic controls, the neocortex of epileptic patients displayed increased levels of superoxide anion (P≤0.001), catalase (P≤0.01), and DNA oxidation (P≤0.001); a decrease in GPx (P≤0.05), and no differences in SOD, GR and lipid peroxidation.
Our findings in humans are in agreement with those found in animal models, supporting oxidative stress as a relevant mechanism also in human epilepsy. The concurrent increase in catalase and decrease in GPx, together with unchanged SOD levels, suggests catalase as the main antioxidant enzyme in human epileptic neocortex. The substantial increase in the levels of O2(-) and 8-oxo-dG in epileptic patients supports a connection between chronic seizures and ROS-mediated neural damage.
No preview · Article · Sep 2013 · Epilepsy research
[Show abstract][Hide abstract] ABSTRACT: Background
Cummings et al, 1987, hypothesized that Alzheimer dementia type (ADT) patientswould present poorer performances than vascular dementia (VD) patients on the neuropsychologicaltests that mainly involve cortical neurological structures, and that VD would perform worse ontests that mainly involve subcortical structures. The main purpose of the research was to identifya cognitive impairment pattern that discriminates the type of dementia in the initial stages.
Two groups of patients, one affected by mild ADT (n = 30) and the other by multi-infarctdementia (VD, n = 30) were given a neuropsychological battery. The battery was composedby Temporal Orientation (Benton et al.); Vocabulary, Similarities, Digits, Coding and Kohs(WAIS) of Wechsler; the Colour-Form Test of Weigl; the Trail Making Test (A and B) (Halstead-Reitan Neuropsychological Battery); Tapping (McQuarrie); Logical Memory, Visual Memory andPaired Association (Wechsler Memory Scale) of Wechsler; Delayed Memory (Russell). The twogroups were similar in age and socio-cultural features. The z-score and its statistical significanceon the Mann-Whitney test were made and we performed an exploratory discriminant analysisto the classification.
In general, results were porer in the ADT group. But we detected no significant differencesin the tests, although some test (Inmediate Visual Memory and Kohs' Blocks) almost reachedsignificance. The discriminant analysis reached a classification of the 67% of the subjectsinto the ADT group and the 70% of the subjects into the VD group.
In the initial stages of dementia it is difficult to differentiate between a corticalpattern of cognitive impairment in ADT and a subcortical pattern in VD, a distinction that theother researchers have reported. When complex tests were used the performance depended onthe coordination of multiple related systems. These findings are in agreement with the holisticmodels of higher mental functions.
No preview · Article · Jul 2013 · Medicina Clínica
[Show abstract][Hide abstract] ABSTRACT: To evaluate the usefulness of ictal electroencephalography (EEG)-combined functional magnetic resonance imaging ( MRI) (EEG-fMRI) in localizing epileptogenic zone in refractory neocortical focal epilepsy.
From the EEG-fMRI database of our institution including 62 adult patients, 14 (age 18-46 years) experienced some ictal event during the test. Data were segmented into 10-s blocks, and the results were analyzed by contrasting each block to the contiguous 10-s block from the onset of seizure onward, in all cases. In seizures lasting >10 s (five cases), a supplementary analysis was performed, contrasting each block to a baseline condition, in the framework of the general linear model (GLM) of analysis. Regions of activations were compared to results from the different techniques performed during presurgical evaluation, such as SISCOM, positron emission tomography (PET), and invasive subdural EEG monitoring.
Regarding the structural MRI findings, nine cases presented some lesion, with blood oxygen level- dependent (BOLD) signal activation placed in the same location in eight of them (89%). SISCOM studies were performed in 11 patients; 5 were concordant with the increase in BOLD signal in a sublobar level, whereas in 3 cases the concordance was in a lobar level. Eleven patients underwent PET studies, being also concordant in a sublobar level in four of them and in a lobar level in four additional cases. Finally, invasive EEG evaluation was performed in three patients and all of them had the seizure-onset zone in the initial area of BOLD activation.
This study adds relevant information to support the integration of EEG-fMRI in the multidisciplinary presurgical workup in patients with refractory epilepsy.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to apply sequential analysis of electroencephalography–functional magnetic resonance imaging (EEG-fMRI) data to study the cortical substrates related to the generation of the interictal epileptiform activity (IEA) in patients with pharmacoresistant extratemporal epilepsy.
We analyzed fMRI data from 21 children, adolescents, and young adults patients who showed frequent bursts or runs of spikes on EEG, by using the sequential analysis method. We contrasted consecutive fixed-width blocks of 10 s to obtain the relative variations in cerebral activity along the entire fMRI runs. Significant responses (p < 0.05, family-wise error (FWE) corrected), time-related to the IEA recorded on scalp EEG, were considered potential IEA cortical sources. These results were compared with those from the fluorodeoxyglucose–positron emission tomography (FDG-PET), intracranial EEG (two patients), and surgery outcome (eight patients).
The typical IEA was recorded in all patients. After the sequential analysis, at least one significant blood oxygen level–dependent (BOLD) response spatially consistent with the presumed epileptogenic zone was found. These IEA-related activation areas coincided when superimposed with the hypometabolism depicted by the FDG-PET. These data were also consistent with the invasive EEG findings. Epileptic seizures were recorded in eight patients. A subset of IEA-associated fMRI activations was consistent the activations at seizure-onset determined by sequential analysis. The inclusion of the IEA-related areas in the resection rendered the patients seizure-free (five of eight operated patients).
The EEG-fMRI data sequential analysis could noninvasively identify cortical areas involved in the IEA generation. The spatial relationship of these areas with the cortical metabolic abnormalities depicted by the FDG-PET and their intrinsic relationship regarding the ictal-onset zone could be useful in epilepsy surgery planning.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Whereas fMRI postprocessing tools used in research are accurate but unwieldy, those used for clinical practice are user-friendly but are less accurate. We aimed to determine whether commercial software for fMRI postprocessing is accurate enough for clinical practice.
Ten volunteers underwent fMRI while performing motor and language tasks (hand, foot, and orolingual movements; verbal fluency; semantic judgment; and oral comprehension). We compared visual concordance, image quality (noise), voxel size, and radiologist preference for the activation maps obtained by using Neuro3D software (provided with our MR imaging scanner) and by using the SPM program commonly used in research.
Maps obtained with the 2 methods were classified as "partially overlapping" for 70% for motor and 72% for language paradigm experiments and as "overlapping" in 30% of motor and in 15% of language paradigm experiments.
fMRI is a helpful and robust tool in clinical practice for planning neurosurgery. Widely available commercial fMRI software can provide reliable information for therapeutic management, so sophisticated, less widely available software is unnecessary in most cases.
No preview · Article · Jan 2013 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: Background
Previous studies in glioblastoma have concluded that there is no decrease in survival with increasing time to initiation of RT up to 6 weeks after surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6 weeks is not small in some countries. The aim of our study was to evaluate the effect of RT delay beyond 6 weeks on survival of patients who have undergone completed resection of a glioblastoma.
We reviewed 107 consecutive glioblastoma patients who had a complete surgical resection at our hospital. Clinical data, including delay in initiation of RT, were prospectively collected. The impact of single parameters on overall survival was determined by univariate and multivariate analyses.
According to univariate analysis, variables that had a prognostic influence on survival were age (p = 0.036), KPS (p = 0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before 42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance scale, additional treatment with chemotherapy, and initiation of RT before 6 weeks after surgery were favorable, independent prognostic factors of survival.
Survival is significantly reduced in glioblastoma patients if RT is not initiated within the 6 weeks after complete resection of the tumor.
[Show abstract][Hide abstract] ABSTRACT: The purpose of our study was to evaluate the performance and clinical usefulness of an automated injector system (AIS) that administers an automated injection for ictal SPECT after calculating the volume of tracer to be injected over time.
To test the AIS, repeated injections were performed at different times after tracer preparation. The clinical study consisted of 56 patients with drug-resistant, complex partial seizures. Tracer for ictal SPECT was injected using automated injection in 27 patients and manual injection (MI) in the remaining 29. Injection time (T(I)) was measured in seconds from seizure onset to the end of volume injection. The SISCOM (Subtraction Ictal Spect Co-registered to MRI) procedure was used to locate the epileptogenic seizure focus with SPECT. The definition of seizure focus was made by consensus of the epilepsy unit using conventional diagnostic methods.
During the experimental phase, there were no system failures, and the error in injected doses when using automated injection was lower than with MI. During the clinical phase, T(I) using manual injection was 41 s with a range of 14-103 s, compared with an AIS average of 33 s with a range of 19-63 s (P < 0.05). Ictal SPECT and SISCOM successfully localized the seizure focus in 21 of the 27 patients (78%) by AIS and in 19 of the 29 patients (65%) by MI (P = 0.14). Furthermore, nursing staff found the AIS method more convenient than the MI method.
An AIS can improve the quality of work of the nursing staff in the neurology ward and allow a finer adjustment of the injection dose. Early results using an AIS would indicate a reduction in injection time and improved SPECT accuracy.
Preview · Article · Feb 2012 · Journal of Nuclear Medicine
[Show abstract][Hide abstract] ABSTRACT: We performed a retrospective chart review of the last consecutive 40 patients admitted in our Epilepsy Unit for presurgical evaluation to find out if they met criteria for drug resistant epilepsy according to the recently published consensus definition. 276 drug trials had been performed in the 40 patients. In total, 196 trials were considered "uninformative" versus 80 informative and adequate trials. Finally, a firm diagnosis of drug resistant epilepsy could be made only in 13/40 patients (32.5%, 90% confidence interval for proportion 21.7-45.5%), due to insufficient information regarding previous drug trials. The definition should be spread among general neurologists for earlier and more complete referrals.
No preview · Article · Dec 2011 · Epilepsy research
[Show abstract][Hide abstract] ABSTRACT: Neuropsychological dysfunction is a major cause of morbidity and mortality after cardiac surgery.
To evaluate if intraoperative cerebral desaturation and depth of anesthesia measured by bispectral index are related to postoperative cognitive dysfunction in cardiac surgery.
Prospective study in patients undergoing elective cardiac surgery with cardiopulmonary bypass. A comprehensive neuropsychological assessment was applied preoperatively and 3 months after surgery. Postoperative dysfunction was defined as a decrease of at least one standard deviation in two or more neuropsychological tests. Cerebral oxygenation and bispectral index were continuously recorded and corrected throughout surgery. Cerebral oxygenation data were analyzed by the mean value and at three thresholds: 50%, 40% and < 25% of the basal value. Bispectral index was analyzed at threshold of 45.
Fifty-six patients were initially enrolled and 48 completed the study. Nine of these (18.8 %) presented postoperative cognitive dysfunction. Mean cerebral saturation and bispectral index data were not different among the patients with or without cognitive dysfunction. There was no association between cerebral desaturation and bispectral index with changes in neurocognitive tests or with length of stay in the intensive care unit. A significant but weak correlation was found between baseline Ray-neurocognitive score and intensive care unit stay (rho = -0.46; P = 0.001).
We did not find a significant association between cerebral desaturation and depth of anesthesia with postoperative cognitive decline in this population of patients.
No preview · Article · Dec 2011 · Revista medica de Chile
[Show abstract][Hide abstract] ABSTRACT: There is an increasing body of evidence implicating eicosanoids (arachidonic acid metabolites) in the experimental generation of epileptic seizures and the development of epilepsy. Our purpose was to measure the synthesis of eicosanoids from the cyclooxygenase and lipoxygenase pathways in human brain neocortex tissue samples obtained from epileptic patients, and to compare them with non-epileptic control subjects. Epileptic neocortex specimens demonstrated a significant increase (P<0.001) in the levels of three eicosanoids derived from the cyclooxygenase pathway: Prostaglandin E(2) (PGE(2)), Thromboxane A(2) (TXA(2)), and Prostacyclin (PGI(2)), compared to controls. In the epileptic samples the level of TXA(2) was twice as much the levels of PGI(2), while in the control samples the levels of PGI(2) were slightly higher than TXA(2). Conversely, there were no detectable levels of eicosanoids derived from the lipoxygenase pathway: Leukotriene B(4) (LTB(4)) and Leukotriene C(4) (LTC(4)). The lack of leukotrienes synthesis illustrates that COX pathway is dominant in neocortex of epileptic patients. Our human data are consistent with the results obtained in experimental animal models of epilepsy. The important increase in PGE(2) and TXA(2) suggests that selective inhibition of prostanoid synthesis or blockage of prostanoid receptors might provide novel antiepileptic strategies in human epilepsy.
No preview · Article · Nov 2011 · Epilepsy research
[Show abstract][Hide abstract] ABSTRACT: Background
The clinical outcome of glioblastoma (GBM) patients who receive radiotherapy alone or with chemotherapy is well established. However, little is known about how many patients do not receive this treatment. We consider it is important to investigate why a proportion of operated patients do not receive further treatment after surgery.
We reviewed all consecutive GBM patients operated on in our hospital between January 2000 and December 2008.
A total of 216 patients with GBM were identified. Fifty-five (25%) did not receive any treatment after surgery. Univariate analysis showed that factors associated with no further treatment after surgery were older than 60 years (p=0.002), of female gender (p=0.03), had a KPS<70 (p<0.001) and had had a biopsy (p<0.001). Multivariate analysis indicated that age ≥60 years and KPS <70 were independent predictors of no further treatment after surgery. Gender was not an independent variable. However, women in the whole series were older than 60 years (p=0.01), and they had a worse KPS (p=0.02) and more biopsies (p=0.04) than men. In the whole group, median survival time was 10.4 months for men (n=125) vs. 7.2 months for women (n=91), log rank p<0.04. This difference was not observed in the group that was treated after surgery.
One out of four patients could not be treated after surgery. Independent predictors were older age and low KPS. These poor risk variables were more frequent in women and their survival was therefore lower than men in our series.
No preview · Article · Oct 2011 · Clinical and Translational Oncology
[Show abstract][Hide abstract] ABSTRACT: Startle epilepsy is a rare form of epilepsy with seizures triggered by unexpected stimuli. Previous studies have suggested the participation of several brain regions, such as the supplementary motor area (SMA) or the mesial aspect of the frontal and parietal lobes in the generation of startle epilepsy. However, how these brain regions interact with each other during seizures remains largely unknown. The aim of this study was to get insight into brain structures involved in startle-induced seizures using an approach with functional neuroimaging.
Four patients with startle epilepsy secondary to unexpected sounds were studied. All of them underwent a presurgical evaluation including ictal-single-emission computed tomography/subtraction ictal SPECT coregistered to MRI (magnetic resonance imaging) (SPECT/SISCOM). We searched for areas with ictal changes of perfusion higher than two standard deviations (2 SD) above the reference. In one patient, a fluorodeoxyglucose-positron emission tomography (FDG-PET) and an ictal electroencephalography-functional MRI (EEG-fMRI) were also performed. In this patient, the results of FDG-PET and sequential analysis of EEG-fMRI were compared to SISCOM.
All the patients had their typical startle-induced seizures, consistent with bilateral asymmetric tonic seizures. Ictal-EEG pattern was located over the mesial centroparietal region in all of them. In three of four patients, a significant hyperperfusion over the mesial frontocentral region was seen, involving the SMA, the perirolandic region, and the precuneus. In one patient, who had a congenital bilateral perisylvian polymicrogyria, it was located over the lateral perirolandic region. 18F-FDG-PET results in the patient in whom it was done, were concordant with SISCOM findings. Ictal EEG-fMRI showed an initial activation located over the precuneus, SMA, cingulate gyrus, and the precentral/perirolandic area.
By using a functional neuroimaging approach we have found that startle-induced seizures could be generated by the interaction of a frontoparietal network located over the mesial surface of the brain.
[Show abstract][Hide abstract] ABSTRACT: Little is known about the long term prognosis of refractory epilepsy patients who do not undergo epilepsy surgery. We performed a telephone survey and chart review of patients who underwent presurgical evaluation in our Unit but did not have surgery, from 1998 until 2004. We contacted 84 patients; mean follow-up was 6.7 years. Four patients (4.7%) had died, presumably of SUDEP. Ten patients (13.1%) were seizure free. In most patients with seizures, frequency remained stable (24/80, 30%) or had decreased by ≥50% (26 patients, 30.9%). Most patients (69, 86.2%) believed their health was similar or better respect to the moment they underwent presurgical evaluation. Employment situation was stable in 64/80 patients (80%), but 11 had received new disability wages. Family situation was also generally unchanged (69/80 patients, 86.2%). Most patients were not taking antidepressants. Seizure free patients scored higher in satisfaction with life. This information can be used to counsel refractory patients.
[Show abstract][Hide abstract] ABSTRACT: Post-operative cognitive dysfunction (POCD) can affect 30% of orthopedic surgery patients. We hypothesized that perioperative temperature has an impact on POCD.
We included 150 patients over 65 years of age scheduled for total knee replacement under spinal anesthesia. They were randomized to receive standard care (sheet cover) or active warming. Neurocognitive assessment (11 subtests) was performed pre-operatively and at day 4 (three subtests) and 3 months (10 subtests). A control group of 55 nonsurgical patients took the same tests at equivalent times. POCD was defined as an individual score decrease of more than 2 standard deviations (SDs) below the baseline on at least two subtests or 2 SDs in the combined z-score, in both cases using control-adjusted changes.
Tympanic temperature declined below 35 °C in 88% of standard-care patients; 25.3% of warmed patients had a temperature ≥36 °C. On day 4, 3.2% of standard-care patients and 19.4% of warmed patients had POCD (P=0.0058). At 3 months, there were no between-group differences (standard care, 14.3%; warmed, 6.5%) (P=0.2440).
Perioperative warming was associated with a higher incidence of cognitive dysfunction at 4 days after total knee replacement in patients >65 years of age.
Full-text · Article · Feb 2011 · Acta Anaesthesiologica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: An open-label, experimental, prospective 5-month follow-up study was performed with 19 patients with psychogenic nonepileptic seizures and anxiety disorder and/or depression who were treated with venlafaxine. The authors held monthly visits and evaluated changes in baseline Hamilton Depression Rating Scale scores, Hamilton Anxiety Rating Scale scores, and the number of psychogenic nonepileptic seizures. HAM-D scores, HAM-A scores, and the number of nonepileptic seizures showed a statistically significant decrease which was maintained over the study period. Based on this study, the authors conclude that venlafaxine may help reduce nonepileptic seizures in patients with additional anxious and/or depressive symptoms.
Full-text · Article · Oct 2010 · The Journal of Neuropsychiatry and Clinical Neurosciences