Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

The proteome of pus from human brain abscesses: host-derived neurotoxic proteins and the cell-type diversity of CNS pus.

OBJECTIVE What determines the extent of tissue destruction during brain abscess formation is not known. Pyogenic brain infections cause destruction of brain tissue that greatly exceeds the area occupied by microbes, as seen in experimental studies, pointing to cytotoxic factors other than microbes in pus. This study examined whether brain abscess pus contains cytotoxic proteins that might explain the extent of tissue destruction. METHODS Pus proteins from 20 human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by proteomics mass spectrometry. Tissue destruction was determined from brain abscess volumes as measured by MRI. RESULTS Brain abscess volume correlated with extracellular pus levels of antibacterial proteins from neutrophils and macrophages: myeloperoxidase (r = 0.64), azurocidin (r = 0.61), lactotransferrin (r = 0.57), and cathelicidin (r = 0.52) (p values 0.002-0.018), suggesting an association between leukocytic activity and tissue damage. In contrast, perfringolysin O, a cytotoxic protein from Streptococcus intermedius that was detected in 16 patients, did not correlate with abscess volume (r = 0.12, p = 0.66). The median number of proteins identified in each pus sample was 870 (range 643-1094). Antibiotic or steroid treatment prior to pus evacuation did not reduce the number or levels of pus proteins. Some of the identified proteins have well-known neurotoxic effects, e.g., eosinophil cationic protein and nonsecretory ribonuclease (also known as eosinophil-derived neurotoxin). The cellular response to brain infection was highly complex, as reflected by the presence of proteins that were specific for neutrophils, eosinophils, macrophages, platelets, fibroblasts, or mast cells in addition to plasma and erythrocytic proteins. Other proteins (neurofilaments, myelin basic protein, and glial fibrillary acidic protein) were specific for brain cells and reflected damage to neurons, oligodendrocytes, and astrocytes, respectively. Pus from subdural empyemas had significantly higher levels of plasma proteins and lower levels of leukocytic proteins than pus from intracerebral abscesses, suggesting greater turnover of the extracellular fluid of empyemas and washout of pus constituents. CONCLUSIONS Brain abscess pus contains leukocytic proteins that are neurotoxic and likely participate actively in the excessive tissue destruction inherent in brain abscess formation. These findings underscore the importance of rapid evacuation of brain abscess pus.

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.

High extracellular concentration of excitatory amino acids glutamate and aspartate in human brain abscess.

Brain abscesses often cause symptoms of brain dysfunction, including seizures, suggesting interference with normal neurotransmission. We determined the concentration of extracellular neuroactive amino acids in brain abscesses from 16 human patients. Glutamate was present at 3.6 mmol/L (median value, range 0.5-10.8), aspartate at 1.0 mmol/L (range 0.09-6.8). For comparison, in cerebroventricular fluid glutamate was ∼0.6 µmol/L, and aspartate was not different from zero. The total concentration of amino acids was higher in eight patients with seizures: 66 mmol/L (median value, range 19-109) vs. 21 mmol/L (range 4-52) in eight patients without seizures (p=0.026). The concentration of aspartate and essential amino acids tryptophan, phenylalanine, tyrosine, leucine, and isoleucine was higher in pus from patients with seizures (p⩽0.040), whereas that of glutamate was not (p=0.095). The median concentration of the non-proteinogenic, inhibitory amino acid taurine was similar in the two groups, 0.7-0.8 mmol/L (range 0.1-6.1). GABA could not be detected in pus. The patient groups did not differ with respect to abscess volume, the cerebral lobe affected, age, or time from symptom onset to surgery. Seven patients with extracerebral, intracranial abscesses had significantly lower pus concentration of glutamate (352 µmol/L, range 83-1368) and aspartate (71 µmol/L, range 22-330) than intracerebral abscesses (p<0.001). We conclude that excitatory amino acids glutamate and aspartate may reach very high concentrations in brain abscesses, probably contributing to symptoms through activation of glutamate receptors in the surrounding brain tissue.

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.