[Acute treatment of patients with severe traumatic brain injury]. / Akutversorgung des Patienten mit schwerem Schädel-Hirn-Trauma.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and permanent disability and a common and important global problem. The contribution of secondary posttraumatic brain damage to overall disability in TBI is significant, underlining the importance of prompt and comprehensive treatment for affected patients. METHODS: This article focuses on current concepts of prehospital and emergency room management of patients with severe TBI to prevent secondary brain injuries. RESULTS AND DISCUSSION: Preclinical prevention and treatment of hypoxia, hypotension and hypercarbia are essential, as they affect the long-term outcome in TBI patients. Prehospital intubation should be critically weighed and in the context of an individual decision. In general, prehospital intubation is more difficult than in the clinical setting. The combination of ketamine and benzodiazepines are commonly used to induce anesthesia before intubation in hemodynamic instable patients. The choice of a muscle relaxant for anesthesia induction is either a non-depolarizing neuromuscular blocking agent or succinylcholine. Administration of mannitol or hypertonic saline is effective to rapidly decrease intracranial pressure. Whenever possible the final destination for transport of TBI patients should be a level I center with round the clock neurosurgical expertise. Trauma-induced coagulopathy should be recognized and immediately treated using a point-of-care testing. CONCLUSION: Hypoxia, hypotension and hypercarbia should strictly be avoided to improve survival and neurological outcome in patients with severe TBI. The prehospital decision to intubate must be made on a case by case basis at the accident site. A level I trauma center should be the destination for this patient group.

Efficacy of BRAF/MEK-inhibitor therapy for epithelioid glioblastoma with a novel BRAFV600 mutation.

Epithelioid glioblastoma (eGB), a very aggressive and rare brain tumour, is associated with a dismal median overall survival. Effective therapies for patients with eGB, particularly with leptomeningeal dissemination, are still lacking. Here, we describe a case of a 25-year-old male diagnosed with an intramedullary cervical tumour with subsequent leptomeningeal disease. Histopathology identified a highly necrotising, epithelioid-type tumour with high cell density, most compatible with the diagnosis of an eGB. DNA analysis revealed an unprecedented B-Raf protooncogene, serine/threonine kinase (BRAF) gene variant in exon 15 (ENST00000288602.6, c.1799_1810delinsATG, p.(V600_W604delinsDG)), triggering activation of the mitogen-activated protein kinase (MAPK) pathway. Consequently, we initiated MAPK inhibitor (MAPKi) therapy, utilizing a combination of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors. Liquid chromatography-tandem mass spectrometry analysis confirmed the drugs' presence in the patient's cerebrospinal fluid, indicating their capacity to cross the blood-brain barrier. Remarkably, the patient responded very well to therapy and transitioned from a near-comatose state to significantly improved health, sustained for over three months. This study highlights that MAPKi, particularly targeted towards novel BRAFV600 mutations, might offer promising advancements in eGB treatment strategies.

The prognostic value of IDH mutations and MGMT promoter status in secondary high-grade gliomas.

Reports about the prognostic value of IDH mutations and the promoter region of the O6-Methyl-guanyl-methyl-transferase gene in secondary high-grade gliomas (sHGG) are few in number. We investigated the prognostic value of IDH mutations and methylation of the promoter region of the MGMT gene in 99 patients with sHGG and analyzed the clinical course of those tumors. Patients with sHGG were screened for IDH mutations by direct sequencing, and, for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction. A total of 48 of 99 patients (48.5 %) had secondary anaplastic gliomas (Group 1), while 51 patients had secondary glioblastomas (Group 2). The median survival time after malignant progression of all patients with sHGG and with an IDH mutation was 4 years, which is significantly longer than in patients with wild-type IDH (1.2 years, p = 0.009). Patients' survival was not significantly influenced by the tumors' MGMT promoter status, both in Group 1- 9.7 years vs. 6.1 years, methylated vs. unmethylated promoter (p = 0.330)-as well as in Group 2-1.5 years vs. 1.6 years, methylated versus unmethylated promoter (p = 0.829). In our population, the IDH mutation status was not associated with increased PFS or median survival time in sGBM patients. However, patients with secondary anaplastic glioma and IDH mutation had a significantly improved outcome. In addition, IDH mutations are a more powerful prognostic marker concerning both PFS and MS than the MGMT promoter status in those patients.

[Chronic subdural hematoma in the elderly]. / Das chronische Subduralhämatom im Alter.

Chronic subdural hematoma (cSDH) is a common condition, the frequency of which further increases due to an aging population and more frequent use of antithrombotic drugs. It leads to unspecific symptoms and neurological deficits and is usually treated surgically. Burr hole trepanation and twist drill craniostomy have become the therapeutic standards with craniotomy being rarely used for recurrent cases. Although recurrences are relatively common, in most cases a good outcome can be achieved even in the elderly; however, as cSDH is associated with other comorbidities, it is indicative of an increased morbidity and mortality. Controlled trials need to be carried out to determine whether pharmacological therapies can also be beneficial in addition to surgical treatment.

[Surgery for metastases, anatomical and ethical limits. Special aspect: oligometastases]. / Metastasenchirurgie - anatomische und ethische Grenzen. Besonderer Aspekt: Oligometastasierung.

The surgical resection of metastases is nowadays feasible in selected patients with multifocal metastatic disease due to the implementation of interdisciplinary multimodal therapeutic options. Anatomical limitations do not seem to represent obstacles which cannot be overcome because of the development of new surgical techniques. The cornerstone of the selection of patients is the correct staging diagnosis achieved through modern diagnostic tools; however, surgery alone does not always offer acceptable survival and recurrence-free rates. Furthermore, in every complex surgical procedure there is the risk of morbidity and mortality; therefore, parameters such as alternative therapeutic modalities, the individual situation of the patient and tumor biology have to be considered in order to make the correct selection of patients. This is one of the major future challenges and should never be driven by unfounded hopes and expectations of the patients. The same principle also applies for brain metastases, which represent the most common brain tumors. Approximately 70 % of patients with brain metastases have 1-3 lesions (oligometastases). Treatment is now individualized and the goal of therapy has shifted towards long-term survival (≥ 24 months) and improved quality of life. Under this aspect surgery is one of the important treatment options, particularly in patients with a single metastasis or oligometastases. Furthermore, approximately 20 % of patients who have recurrent brain metastases, successfully undergo a complete resection of tumors and with a Karnofsky performance status (KPS) score > 70 show a long-term survival of ≥ 24 months.