Predictive value of metabolic and perfusion changes outside the seizure onset zone for postoperative outcome in patients with refractory focal epilepsy.

The value of functional molecular changes outside the seizure onset zone as independent predictive factors of surgical outcome has been scarcely evaluated. The aim of this retrospective study was to evaluate relative metabolic and perfusion changes outside the seizure onset zone as predictors of postoperative outcome in patients with unifocal refractory focal epilepsy. Eighty-six unifocal epilepsy patients who underwent 18F-FDG PET prior to surgery were included. Ictal and interictal perfusion SPECT was available in 65 patients. Good postoperative outcome was defined as the International League against Epilepsy class 1. Using univariate statistical analysis, the predictive ability of volume-of-interest based relative metabolism/perfusion for outcome classification was quantified by AUC ROC-curve, using composite, unilateral cortical (frontal, orbitofrontal, temporal, parietal, occipital) and central volumes-of-interest. The results were cross-validated, and a false discovery rate (FDR) correction was applied. As a secondary objective, a subgroup analysis was performed on temporal lobe epilepsy patients (N = 64). Increased relative ictal perfusion in the contralateral central volume-of-interest was significantly associated with the good surgical outcome both in the total population (AUC 0.79, pFDR = 0.009) and the temporal lobe epilepsy subgroup (AUC 0.80, pFDR = 0.028). No other significant associations between functional molecular changes and postoperative outcome were found. Increased relative ictal perfusion in the contralateral central region significantly predicted outcome after epilepsy surgery in patients with refractory focal epilepsy. We postulate that these relative perfusion changes could be an expression of better preoperative neuronal network integration and centralization in the contralateral central structures, which is suggested to be associated with better postoperative outcome.

DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival.

BACKGROUND: Histologically classified glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy, and clinical outcome. METHODS: 450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells, and Programmed cell death protein 1 (PD-1) expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy. RESULTS: Forty-two tumors had a mesenchymal, 27 a receptor tyrosine kinase (RTK) II, 17 RTK I, and 7 an isocitrate dehydrogenase (IDH) DNA methylation pattern. Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells, and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 mo), intermediate in RTK II tumors (27 mo), and significantly lower in mesenchymal and RTK I groups (15.5 and 16 mo, respectively). CONCLUSIONS: Methylation based stratification of GBM is related to T-cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.

Vagus nerve stimulation in children with drug-resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy?

AIM: To study the efficacy of vagus nerve stimulation (VNS) therapy in a highly drug-resistant childhood epilepsy patient group and to investigate the effect of age at implantation on efficacy. METHODS: The efficacy of VNS treatment was analysed in a cohort of 70 patients with drug-resistant epilepsy. Both children with focal (n=16) and generalized epilepsies (n=54) were included. Age at implantation varied between 19 months and 25 years. RESULTS: Overall, responder rate was 54% with 5.7% children becoming seizure-free. The only factor in our analysis that could predict good outcome was age at implantation. In the youngest group (<5 years), the responder rate was 77% and this group also included three of the four seizure-free children. These three seizure-free children were known to have tuberous sclerosis. There were no outcome differences between generalized and focal epilepsies. CONCLUSIONS: Our single centre study confirms previous studies on the efficacy of VNS in children. A larger study using multivariate analysis to disentangle the contribution of different factors (such as age at implantation, aetiology, and epilepsy duration) is necessary to confirm our preliminary finding that younger age at VNS implantation might result in a better outcome.

Acquired cerebellar cavernous angioma following childhood radiotherapy in a patient with neurofibromatosis type 1.

We report the unusual case of a patient with neurofibromatosis type I, who was irradiated 16 years previously for a mesencephalic glioma causing hydrocephalus, and who developed a cerebellar haemorrhage caused by a histologically confirmed cavernous angioma, that was invisible on several earlier MRI scans. The different hypotheses concerning the de novo formation of cavernous angiomas (venous obstructive disease and genetic abnormalities) are succinctly reviewed.

Treatment of a giant basilar artery aneurysm with a bridging stent and subsequent coil occlusion of the stent: case report.

OBJECTIVE AND IMPORTANCE: To report the treatment of a symptomatic giant basilar artery aneurysm in a child. CLINICAL PRESENTATION: A 7-year-old girl presented with a 2-month history of progressive right hemiparesis caused by a huge fusiform aneurysm of the basilar artery with compression of the brainstem. INTERVENTION OR TECHNIQUE: The patient was treated with a bridging bare stent and occlusion of the stent lumen with detachable coils. CONCLUSION: The patient experienced immediate total occlusion of the aneurysm with almost total recuperation after 1 year.

A clinical analysis of 4- and 6-year follow-up results after cervical disc replacement surgery using the Bryan Cervical Disc Prosthesis.

OBJECT: In this study, long-term results are presented from clinical studies of the Bryan Cervical Disc Prosthesis at University Hospital Gasthuisberg in Leuven, Belgium. A total of 98 patients (89 with 1-level and 9 with 2-level implantations) agreed to participate in follow-up studies for up to 10 years postoperatively. This article focuses on the 4- and 6-year results. Patients in one of the clinical studies had either radiculopathy or myelopathy associated with spondylosis and/or disc herniations that did not respond to conservative treatment. Patients from the other clinical study received commercially available Bryan devices and the study protocol did not have specific inclusion/exclusion criteria. More than 90% of the patients were considered to have radiculopathy. METHODS: Clinical measurements discussed in the article include the 36-Item Short Form Health Survey, Neck Disability Index, numerical ratings of neck and arm pain, neurological outcomes, and Odom classification. Angular motion findings from lateral flexion-extension radiographs are also presented. The occurrence of adverse events and second surgeries are examined as an indicator of device safety. RESULTS: The clinical outcomes at 4 and 6 years postoperatively appear consistent with the previously reported results at 1 and 2 years postoperatively. The mean angular motion results at 4 and 6 years postoperatively for 1-level patients were 7.3 and 7.7 degrees, respectively. Two-level patients had slightly less motion at 4 and 6 years postoperatively with mean caudad values of 5.7 and 6.0 degrees, respectively, and cephalad values of 4.2 and 6.2 degrees, respectively. Efforts were made to capture adverse events, regardless of their nature and relatedness to the study surgery. This effort resulted in a relatively high number of recorded events. However, only 6 patients experienced events that were judged by the investigator to be related, either possibly or definitely, to the Bryan device. These events included device migration, device removal, and hoarseness and vocal cord paralysis, as well as 3 cases involving pain and neurological symptoms. Eight patients underwent further neck surgery to treat symptoms. CONCLUSIONS: The favorable clinical and angular motion outcomes that were previously noted at 1- and 2-years' follow-up after cervical disc replacement with the Bryan Cervical Disc Prosthesis appear to persist after 4 and 6 years of follow-up.

Longitudinal prospective long-term radiographic follow-up after treatment of single-level cervical disk disease with the Bryan Cervical Disc.

BACKGROUND: Many short- and intermediate-term radiological and clinical studies on cervical arthroplasty with the Bryan Cervical Disc have been published, providing, most of the time, satisfactory results. OBJECTIVE: To prospectively assess the intermediate and long-term radiographic characteristics of disk replacement surgery with the Bryan Cervical Disc and to correlate these results with clinical outcome. METHODS: Range of motion was measured with a validated tool. Intervertebral disk degeneration was assessed with a quantitative scoring system. Heterotopic ossification was evaluated with a previously published scoring system. Device stability was investigated by measuring subsidence and anteroposterior migration. General clinical patient outcome was assessed with the Odom classification system. RESULTS: Eighty-nine patients were initially included in this prospective long-term study. One patient was reoperated on at the index level and 4 were reoperated on at an adjacent level; those patients were not further analyzed. The mobility at the treated level was preserved in > or = 85% of our cases. The insertion of the prosthesis did not lead to an increase in mobility at the adjacent levels. The degeneration score increased at both adjacent levels. Heterotopic ossification was present in 34% to 39% of the patients, depending on the follow-up point. No cases of anteroposterior migration or subsidence were found. More than 82% of all patients had a good to excellent clinical outcome in the long run. CONCLUSION: The device maintains preoperative motion at the index and adjacent levels, seems to protect against acceleration of adjacent-level degeneration as seen after anterior cervical discectomy and fusion, and remains securely anchored in the adjacent bone mass in the long run. Heterotopic ossification was frequently seen. The vast majority of all patients had a good to excellent clinical outcome.

Long-term follow-up after interbody fusion of the cervical spine.

The aim of this work was to add to the body of data on the frequency and severity of degenerative radiographic findings at adjacent levels after anterior cervical interbody fusion and on their clinical impact and to contribute to the insights about their pathogenesis. One hundred eighty patients who were treated by anterior cervical interbody fusion and who had a follow-up of >60 months were clinically and radiologically examined by independent investigators. For all patients, the long-term Odom score was compared with the score as obtained 6 weeks after surgery. For myelopathic cases, both the late Nurick and the Odom score were compared with the initial postoperative situation. For the adjacent disc levels, a radiologic "degeneration score" was defined and assessed both initially and at long-term follow-up. At late follow-up after anterior cervical interbody fusion, additional radiologic degeneration at the adjacent disc levels was found in 92% of the cases, often reflecting a clinical deterioration. The severity of this additional degeneration correlated with the time interval since surgery. The similarity of progression to degeneration between younger trauma patients and older nontrauma patients suggests that both the biomechanical impact of the interbody fusion and the natural progression of pre-existing degenerative disease act as triggering factors for adjacent level degeneration.