Brain tumors in children with refractory seizures­a long-term follow-up study after epilepsy surgery.

PURPOSE: Epilepsy surgery is an established treatment option for medically refractory epilepsy. Brain tumors, besides dysplasias, vascular malformations, and other lesions, can cause refractory epilepsy. Long-term epilepsy-associated brain tumors, even though mostly benign, are neoplastic lesions and thus have to be considered as both epileptic and oncological lesions. METHODS: We retrospectively analyzed epileptological and oncological long-term follow-up (FU) in pediatric patients who underwent brain surgery for refractory epilepsy and whose histology showed a tumor as underlying cause (n = 107, mean FU 119 months). RESULTS: At last available outcome, 82.2% of patients were seizure free (International League Against Epilepsy (ILAE) class 1) and seizure outcome was stable over more than 14 years. Fifty-four percent of the patients were without anti-epileptic drugs (AEDs) at last available outcome; 96.2% of the tumors were classified WHO grade I and II and 3.7% were malignant (WHO grade III). Adjuvant treatment was administered in 5.7%; 2.9% had relapse and one patient died (tumor-related mortality = 1.4%). After surgery, 91% of the patients attended regular school/university and/or professional training. CONCLUSIONS: This study shows that epileptological outcome within this group is promising and stable and oncological outcome has a very good prognosis. However, oncological FU must not be dismissed as a small percentage of patients who suffer from malignant tumors and adjuvant treatment, relapse, and mortality have to be considered.

Safety, feasibility and complications during resective pediatric epilepsy surgery: a retrospective analysis.

BACKGROUND: Resective epilepsy surgery is an established and effective method to reduce seizure burden in drug-resistant epilepsy. It was the objective of this study to assess intraoperative blood loss, transfusion requirements and the degree of hypothermia of pediatric epilepsy surgery in our center. METHODS: Patients were identified by our epilepsy surgery database, and data were collected via retrospective chart review over the past 25 years. Patients up to the age of 6 years were included, and patients with insufficient data were excluded. RESULTS: Forty-five patients with an age of 3.2 ± 1.6 (mean ± SD) years and a body weight of 17 [14; 21.5] kg (median [25%, 75% percentile]) were analysed. Duration of surgery was 3 h 49 min ± 53 min, which was accompanied by an intraoperative blood loss of 150 [90; 300] ml. This corresponded to 11.7 [5.2; 21.4] % of estimated total blood volume, ranging from 0 to 75%. A minimal haemoglobin count of 8.8 ± 1.4 g/dl was measured, which was substituted with erythrocyte concentrate (100 [0; 250] ml) in 23 patients. Body core temperature dropped from 36.0 ± 0.7°C at baseline to a minimum of 35.7 ± 0.7°C, and increased significantly (p < 0.001) thereafter to 37.1 ± 0.7°C until the end of surgery. A significant (p = 0.0003) correlation between duration of surgery and blood loss (Pearson r = 0.52) was observed. However, age, minimal body temperature or number of antiepileptic drugs seemed to have no impact on blood loss. CONCLUSION: Resective epilepsy surgery is a safe procedure even in the pediatric population, however it is associated with significant blood loss especially during long surgical procedures.

Systematic symptom screening in patients with advanced cancer treated in certified oncology centers: results of the prospective multicenter German KeSBa project.

PURPOSE: Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC. METHODS: The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results. RESULTS: Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC-) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC- CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC- CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often. CONCLUSION: Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources.

Therapeutic inhibition of FcγRIIb signaling targets leukemic stem cells in chronic myeloid leukemia.

Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcγRIIb, CD32b) for being critical in LSC resistance and show that targeting FcγRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach. First, we identified FcγRIIb upregulation in primary CML stem cells. FcγRIIb depletion caused reduced serial re-plaiting efficiency and cell proliferation in malignant cells. FcγRIIb targeting in both a transgenic and retroviral CML mouse model provided in vivo evidence for successful LSC reduction. Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcγRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.

Behr syndrome with homozygous C19ORF12 mutation.

OBJECTIVE: Behr syndrome, first described in 1909 by the ophthalmologist Carl Behr, is a clinical entity characterised by a progressive optic atrophy, ataxia, pyramidal signs and mental retardation. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder. METHODS: We present the long-term observation of two Turkish sisters with Behr syndrome. We performed neurophysiological, imaging and molecular genetic studies to identify the underlying genetic cause in our patients. RESULTS: Magnetic resonance imaging of the brain showed bilateral hypointense signals in the basal ganglia which prompted us to consider neurodegeneration with brain iron accumulation (NBIA) as a differential diagnosis. Molecular genetic studies revealed a homozygous mutation in the C19ORF12 gene which has been previously reported in patients with a subtype of NBIA, mitochondrial membrane protein-associated neurodegeneration (MPAN). CONCLUSION: We expand the spectrum of genetic causes of Behr syndrome. Genetic testing of patients presenting with Behr syndrome should include C19ORF12 mutation screening.