Seizure outcomes of temporal lobe epilepsy surgery in patients with normal MRI and without specific histopathology.

BACKGROUND: Seizure outcome following surgery in pharmacoresistant temporal lobe epilepsy patients with normal magnetic resonance imaging and normal or non-specific histopathology is not sufficiently presented in the literature. METHODS: In a retrospective design, we reviewed data of 263 patients who had undergone temporal lobe epilepsy surgery and identified 26 (9.9%) who met the inclusion criteria. Seizure outcomes were determined at 2-year follow-up. Potential predictors of Engel class I (satisfactory outcome) were identified by logistic regression analyses. RESULTS: Engel class I outcome was achieved in 61.5% of patients, 50% being completely seizure free (Engel class IA outcome). The strongest predictors of satisfactory outcome were typical ictal seizure semiology (p = 0.048) and localised ictal discharges on scalp EEG (p = 0.036). CONCLUSION: Surgery might be an effective treatment choice for the majority of these patients, although outcomes are less favourable than in patients with magnetic resonance imaging-defined lesional temporal lobe epilepsy. Typical ictal seizure semiology and localised ictal discharges on scalp EEG were predictors of Engel class I outcome.

Seizure outcomes in relation to the extent of resection of the perifocal fluorodeoxyglucose and flumazenil PET abnormalities in anteromedial temporal lobectomy.

BACKGROUND: The area of predominant perifocal [(18)F]fluorodeoxyglucose ((18)F-FDG) hypometabolism and reduced [(11)C]flumazenil ((11)C-FMZ) -binding on PET scans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE). The question is whether the volume of the perifocal pre-operative PET abnormalities, the extent of their resection, and the volume of the non-resected abnormalities affects the post-operative seizure outcome. METHODS: The sample group consisted of 32 patients with mesial temporal sclerosis who underwent anteromedial temporal lobe resection for refractory TLE. All patients had pathologic perifocal findings on both of the PET modalities as well as on the whole-brain MRI. The volumetric data of the PET and MRI abnormalities within the resected temporal lobe were estimated by automated quantitative voxel-based analysis. The obtained volumetric data were investigated in relation to the outcome subgroups of patients (Engel classification) determined at the 2-year post-operative follow-up. RESULTS: The mean volume of the pre-operative perifocal (18)F-FDG- and (11)C-FMZ PET abnormalities in the volumes of interest (VOI) of the epileptogenic temporal lobe, the mean resected volume of these PET abnormalities, the mean volume of the non-resected PET abnormalities, and the mean MRI-derived resected volume were not significantly related to the outcome subgroups and had a low prediction for individual freedom from seizures. CONCLUSIONS: The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE.

Volume and densities of chronic subdural haematoma obtained from CT imaging as predictors of postoperative recurrence: a prospective study of 107 operated patients.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common entity in neurosurgery with a considerable postoperative recurrence rate. Computerised tomography (CT) scanning remains the most important diagnostic test for this disorder. The aim of this study was to characterise the relationship between the recurrence of CSDH after treatment with burr-hole irrigation and closed-system drainage technique and CT scan features of these lesions to assess whether CT findings can be used to predict recurrence. METHODS: We investigated preoperative and postoperative CT scan features and recurrence rate of 107 consecutive adult surgical cases of CSDH and assessed any relationship with univariate and multivariate regression analyses. RESULTS: Seventeen patients (15.9 %) experienced recurrence of CSDH. The preoperative haematoma volume, the isodense, hyperdense, laminar and separated CT densities and the residual total haematoma cavity volume on the 1st postoperative day after removal of the drainage were identified as radiological predictors of recurrence. If the preoperative haematoma volume was under 115 ml and the residual total haematoma cavity volume postoperatively was under 80 ml, the probability of no recurrence was very high (94.4 % and 97.4 % respectively). CONCLUSIONS: These findings from CT imaging may help to identify patients at risk for postoperative recurrence.

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study.

OBJECTIVE AND DESIGN: Innate immune pro- and anti-inflammatory responses in patients with chronic subdural hematoma (CSDH) were investigated by measuring and comparing the systemic and subdural fluid levels of cytokines. MATERIALS AND METHOD: Cytokine values were analyzed in samples obtained during surgery of 56 adult patients who were operated on for unilateral CSDHs using a Multiplex antibody bead kit. RESULTS: There were significantly higher levels of the pro-inflammatory IL-2R (p = 0.004), IL-5 (p < 0.001), IL-6 (p < 0.001), and IL-7 (p < 0.001), and anti-inflammatory mediators IL-10 (p < 0.001) and IL-13 (p = 0.002) in CSDH fluid compared with systemic levels. The pro-inflammatory TNF-alpha (p < 0.001), IL-1beta (p < 0.001), IL-2 (p = 0.007) and IL-4 (p < 0.001) were significantly lower in hematoma fluid compared with systemic levels. The ratios between pro- versus anti-inflammatory cytokines were statistically significant higher in CSDH (7.8) compared with systemic levels (1.3). CONCLUSIONS: The innate immune responses occur both locally at the site of CSDH, as well as systematically in patients with CSDH. The local hyper-inflammatory and low anti-inflammatory responses exist simultaneously. The findings suggest poorly coordinated innate immune responses at the site of CSDH that may lead to propagating of local inflammatory process and basically contribute to formation and progression of CSDH.

Chemokines as markers of local inflammation and angiogenesis in patients with chronic subdural hematoma: a prospective study.

OBJECTIVE: The goal of this study was to investigate the chemokines CCL2, CXCL8, CXCL9 and CXCL10 as markers of the inflammatory responses in chronic subdural hematoma (CSDH). METHODS: Samples of peripheral venous blood and CSDH fluid (obtained during surgery) in 76 adult patients were prospectively analyzed. Chemokine values were assessed by a Multiplex antibody bead kit. RESULTS: We found significantly higher levels of chemokines CCL2, CXCL8, CXCL9 and CXCL10 in hematoma fluid compared with serum. CONCLUSIONS: Chemokines are elevated in the hematoma cavity of patients with CSDH. It is likely that these signaling modulators play an important role in promoting local inflammation. Furthermore, biological activity of CCL2 and CXCL8 may promote neovascularization within the outer CSDH membrane, and a compensatory angiostatic activity of CXCL9 and CXCL10 may contribute to repairing this disorder. This phenomenon was restricted to the hematoma site, and the systemic chemokine levels might not reflect local immune responses.

Association between biomarkers and clinical characteristics in chronic subdural hematoma patients assessed with lasso regression.

Chronic subdural hematoma (CSDH) is characterized by an "old" encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura). Recognized risk factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data, but lasso regression revealed an association with inflammatory and angiogenic biomarkers in hematoma fluid. We thus suggest that lasso regression should be a recommended statistical method in research on biological processes in CSDH patients.

A Reliable Grading System for Prediction of Chronic Subdural Hematoma Recurrence Requiring Reoperation After Initial Burr-Hole Surgery.

BACKGROUND: There is no widely adopted grading system for the prediction of postoperative recurrence requiring reoperation (RrR) in patients with chronic subdural hematoma (CSDH). OBJECTIVE: We developed a CSDH grading system to predict RrR based on predictive characteristics that can be objectively assessed at the time of first presentation and initial surgery. METHODS: Prospectively collected data from 107 consecutive surgical patients with CSDH were reviewed. Predictors of RrR were identified via logistic and lasso regression analyses. A prognostic CSDH grading system was proposed, with the weighing of predictors based on strength of association. The scoring system was then applied to the same set of patients in our database for internal validation. RESULTS: The strongest predictors of RrR were an isodense or hyperdense lesions and laminar or separated lesions, and a postoperative CSDH cavity volume greater than 200 mL. The moderate predictors of RrR were a postoperative CSDH cavity volume of 80 to 200 mL and a preoperative CSDH volume greater than 130 mL. According to the prognostic CSDH grading system, no patients with a score of 0 points had RrR. RrR was observed in 6% of patients with a score of 1 to 2 points, 30% of patients with a score of 3 to 4 points, and 63% of patients with a score of 5 points (ie, the maximum score). The rate of RrR increased steadily with increases in the prognostic CSDH grading score (P < .001). CONCLUSION: The prognostic CSDH grading system is an applicable tool for RrR risk stratification in patients with CSDH.

The correlation between pro- and anti-inflammatory cytokines in chronic subdural hematoma patients assessed with factor analysis.

Chronic subdural hematoma (CSDH) is a relatively common disorder in neurosurgery on elderly patients, though the mechanism that causes the disease remains unclear. Studies have suggested that local anticoagulation and inflammatory changes may be important in its pathogenesis. Most studies have used a basic bivariate statistical analysis to assess complex immunological responses in patients with this disorder, hence a more sophisticated multivariate statistical approach might be warranted. Our objective was to assess the association and correlation between the pro- and anti-inflammatory responses in a cohort of patients with chronic subdural hematoma (n=57) using an exploratory and confirmatory factor analysis. Thirteen assigned pro-inflammatory (TNF-α, IL-1ß, IL-2, IL-2R, IL-6, IL-7, IL-12, IL-15, IL-17, CCL2, CXCL8, CXCL9 and CXCL10) and five assigned anti-inflammatory (IL-1RA, IL-4, IL-5, IL-10 and IL-13) cytokines from blood and hematoma fluid samples were examined. Exploratory factor analysis indicated two major underlying immunological processes expressed by the cytokines in both blood and hematoma fluid, but with a different pattern and particularly regarding the cytokines IL-13, IL-6, IL-4 and TNF-α. Scores from confirmatory factor analysis models exhibited a higher correlation between pro- and anti-inflammatory activities in blood (r=0.98) than in hematoma fluid samples (r=0.92). However, correlations of inflammatory processes between blood and hematoma fluid samples were lower and non-significant. A structural equation model showed a significant association between increased anti-inflammatory activity in hematoma fluid samples and a lower risk of recurrence, but this relationship was not statistically significant in venous blood samples. Moreover, these findings indicate that anti-inflammatory activities in the hematoma may play a role in the risk of a recurrence of CSDH.

Cerebral microdialysis and intracranial pressure monitoring in patients with idiopathic normal-pressure hydrocephalus: association with clinical response to extended lumbar drainage and shunt surgery.

OBJECT: This study was performed in patients with idiopathic normal-pressure hydrocephalus (iNPH) to monitor cerebral metabolism with microdialysis (MD) and intracranial pressure (ICP) readings, and relate to the clinical responses to extended lumbar drainage (ELD) and shunt surgery. METHODS: The baseline levels of MD metabolites and ICP were monitored overnight in 40 consecutive patients with iNPH. In a subset of 28 patients, monitoring was continued during 3 days of ELD. Thirty-one patients received a ventriculoperitoneal shunt. The clinical severity of iNPH was determined before and then 3 and 6-12 months after shunt surgery. RESULTS: Altered levels of MD markers (lactate, pyruvate, lactate/pyruvate ratio, glutamate, and/or glycerol) were seen in all patients at baseline; these improved during ELD. Despite normal static ICP (mean ICP), the pulsatile ICP (the ICP wave amplitude) was increased in 24 patients (60%). Only the level of the ICP wave amplitude differentiated the ELD and/or shunt responders from nonresponders. CONCLUSIONS: The MD monitoring indicated low-grade cerebral ischemia in patients with iNPH; during ELD, cerebral metabolism improved. The pulsatile ICP (the ICP wave amplitude) was the only variable differentiating the clinical responders from the nonresponders. The authors suggest that the pulsatile ICP reflects the intracranial compliance and that CSF diversion improves the biophysical milieu of the nerve cells, which subsequently may improve their biochemical milieu.