Aging-associated weakening of the action potential in fast-spiking interneurons in the human neocortex.

Aging is associated with the slowdown of neuronal processing and cognitive performance in the brain; however, the exact cellular mechanisms behind this deterioration in humans are poorly elucidated. Recordings in human acute brain slices prepared from tissue resected during brain surgery enable the investigation of neuronal changes with age. Although neocortical fast-spiking cells are widely implicated in neuronal network activities underlying cognitive processes, they are vulnerable to neurodegeneration. Herein, we analyzed the electrical properties of 147 fast-spiking interneurons in neocortex samples resected in brain surgery from 106 patients aged 11-84 years. By studying the electrophysiological features of action potentials and passive membrane properties, we report that action potential overshoot significantly decreases and spike half-width increases with age. Moreover, the action potential maximum-rise speed (but not the repolarization speed or the afterhyperpolarization amplitude) significantly changed with age, suggesting a particular weakening of the sodium channel current generated in the soma. Cell passive membrane properties measured as the input resistance, membrane time constant, and cell capacitance remained unaffected by senescence. Thus, we conclude that the action potential in fast-spiking interneurons shows a significant weakening in the human neocortex with age. This may contribute to the deterioration of cortical functions by aging.

Minimal invasive transnasal endoscopic removal of intracranial foreign body after airbag deployment.

Airbag induced injuries such as skull and cervical spine fractures, epidural and subdural hematomas, atlantooccipital dislocations or brainstem lacerations are already documented in published literature, however, no previous case have been published about a penetrating foreign body of the skull base following airbag deployment. Removal of an intracranial foreign body is very dangerous and difficult, or even if it possible and necessary, requires open surgery in most of the cases. In this article we present the minimal invasive, transnasal removal of a coin from the intracranial, frontobasal region using high-resolution endoscopy combined with image-guided navigation.
We report the case of a 59-year-old male who was brought to the emergency department after a car accident. He suffered a penetrating injury by a coin that was placed on the car’s airbag at the moment of the accident. Upon the airbag being deployed the foreign body entered the skin through the right lower eyelid, crossing the orbital cavity, ethmoid cells, sphenoid sinus and the anterior part of the planum sphenoidale at an equal distance of 2mm from the two internal carotid arteries, extending into the intracranial space, without injuring the pituitary stalk and the chiasm. We proceeded to remove the coin endoscopically using a transnasal transseptal transsphenoidal approach under general anesthesia. The dura was closed with a multilayer skull base reconstruction technique using two layers of abdominal free fat and nasal septal mucoperiosteal flap. There were no postoperative complications, nor CSF rhinorrhea. The patient was discharged 10 days after the operation.
To our knowledge, this is the first publi­shed case of a penetrating foreign body of the skull base, extending into the intracranial cavity following airbag deployment. In some dedicated cases, a minimal invasive endoscopic approach should be considered as an alternative to anterior craniotomy if access is possible when foreign bodies from the skull base area need to be removed. This procedure is efficient, safe and minimally invasive. 

Temporal disparity of action potentials triggered in axon initial segments and distal axons in the neocortex.

Neural population activity determines the timing of synaptic inputs, which arrive to dendrites, cell bodies, and axon initial segments (AISs) of cortical neurons. Action potential initiation in the AIS (AIS-APs) is driven by input integration, and the phase preference of AIS-APs during network oscillations is characteristic to cell classes. Distal regions of cortical axons do not receive synaptic inputs, yet experimental induction protocols can trigger retroaxonal action potentials (RA-APs) in axons distal from the soma. We report spontaneously occurring RA-APs in human and rodent cortical interneurons that appear uncorrelated to inputs and population activity. Network-linked triggering of AIS-APs versus input-independent timing of RA-APs of the same interneurons results in disparate temporal contribution of a single cell to in vivo network operation through perisomatic and distal axonal firing.

[The benefits of a hybrid operation room in neurosurgery.] / A hibrid muto elonyei idegsebészeti mutétek során.

INTRODUCTION: The hybrid operation room - with a robotic arm equipped angiographic device - started its operation in November 2019 at the Department of Neurosurgery, Szeged, Hungary. OBJECTIVE: We report the benefits of the hybrid operation room in the neurosurgery practice based on our results and experiences of the last 1.5 years. METHOD: 576 operations took place between 15. 11. 2019 and 01. 03. 2021, which include 332 neurointerventions amd 244 skull-brain and spine surgeries. By using Siemens ARTIS pheno®, we performed purely catheter only interventions or surgical only interventions, but combined treatments were also performed in several cases (catheter and surgical intervention). Thanks to ARTIS pheno® versatility, it is used as a modern imaging system in preoperative examination or as navigation system in spine surgery and control imaging for intra- and postoperative examinations. DISCUSSION: We created three categories based on the results of the last months according to the need of using the hybrid operation room for the given operation: (1) strongly recommended, (2) recommended, (3) advantageous. Strongly recommended: if the two teams (surgical and interventional team) have to work together during the operation. Recommended: if the two teams are not participating together in the operation, but the other team is on standby and may join the operation if necessary. Advantageous: this category means the possibility of performing control imaging before the wound closure. CONCLUSION: Based on our experience, the hybrid operation room provides significant help in neurosurgery. It has become part of our daily care, and we think it is indispensable in the work of a neurosurgery center. Orv Hetil. 2023; 164(43): 1701-1711.

Case Report: Brainstem angiocentric glioma presenting in a toddler child-diagnostic and therapeutic challenges.

Introduction: Angiocentric gliomas (AG) in brainstem location are exceedingly rare and might cause differential diagnostic problems and uncertainty regarding the best therapeutic approach. Hereby, we describe the clinicopathological findings in a brainstem AG presenting in a toddler child and review the literature. Case report: A 2-year-old boy presented with 5 weeks history of gait disturbances, frequent falls, left-sided torticollis and swallowing problems. MRI head showed a T2-hyperintense, partly exophytic mass lesion centred in the pontomedullary region, raising the possibility of diffuse midline glioma. The exophytic component was partially resected by suboccipital craniotomy, leaving intact the infiltrative component. Ventriculoperitoneal shunt was implanted due to postoperative hydrocephalus. Histological examination revealed a moderately cellular tumour consisted of bland glial cells infiltrating the brain parenchyma and radially arranged around the blood vessels. By immunohistochemistry, the tumour strongly expressed S100 and GFAP in addition to intense nestin positivity, while OLIG2 was negative in the perivascular tumour cells. DNA methylation array profiled the tumour as "methylation class diffuse astrocytoma, MYB or MYBL1-altered subtype B (infratentorial)" and an in-frame MYB::QKI fusion was identified by RNA sequencing, confirming the diagnosis of angiocentric glioma. The patient has been initially treated with angiogenesis inhibitor and mTOR inhibitor, and now he is receiving palliative vinblastine. He is clinically stable on 9 months follow-up. Conclusion: Brainstem AG may cause a diagnostic problem, and the surgical and oncological management is challenging due to unresectability and lack of response to conventional chemo-radiation. In the future, genetically-tailored therapies might improve the prognosis.

[Neurosurgical management for metastatic brain tumors in renal cell carcinoma]. / Oligometasztatikus vesesejtes karcinóma idegsebészi ellátásának technikái és indikációi agyi áttétek esetén.

The therapeutic approach to brain metastases has changed significantly in the last 30 years. The development of surgical technique, the use of new MRI techniques, preoperative surgical planning and the administration of intraoperative navigation reduced the risks of surgery and improved the results. In the case of aggressive renal cell carcinomas, we detect brain metastases relatively often, which are difficult to treat, but the improved surgical and radiosurgery techniques can also be used with success. In our report, we present the neurosurgical management of metastatic spreading of renal cell carcinoma to the brain. Modern surgical planning and more precise, tailored approach with modern radiosurgery techniques are able to improve the outcome and prolong survival even in aggressive types of renal cell carcinomas that give rise to brain metastases. In more severe cases and even in the case of multiple brain metastases, cranial surgery can be recommended.

[Techniques and indications of neurosurgical treatment of oligometastatic renal cell carcinomas in case of spinal metastases]. / Oligometasztatikus vesesejtes karcinóma idegsebészi ellátásának technikái és indikációi gerincáttétek esetén.

The treatment of spinal metastases is a huge challenge, but both oncological and surgical treatment have improved significantly. Spine surgeons use the experience of spine surgeries performed for an increased number of degenerative causes during spine surgeries performed for an increased number of tumors. Establishing an indication for surgery is at least as much of a challenge as the surgery itself, for which there are many objective point systems available. Renal cell carcinoma metastases are less sensitive to radiation, which is why careful surgery is even more important. In our short summary, we review the symptoms, the examination, the grading systems used and the surgical options.

Percutaneous Superficial Temporal Artery Access Facilitating Carotid Artery Stenting Performed From Distal Radial Artery.

PURPOSE: The purpose of the study is to describe carotid artery stenting (CAS) via distal transradial access (dTRA) facilitated by additional superficial temporal artery (STA) access, in a patient with complex aortic arch vessel anatomy. TECHNIQUE: A 72-year-old woman with a prior history of complex cervical surgery and radiotherapy due to laryngeal malignancy, presented with a symptomatic 90% stenosis of the left internal carotid artery (ICA). Due to high cervical lesion, the patient was rejected from carotid endarterectomy. Angiography demonstrated 90% stenosis of the left ICA and a type III aortic arch. After failure of left common carotid artery (CCA) cannulation with appropriate catheter support via dTRA and transfemoral approaches, CAS was attempted a second time. After percutaneous ultrasound guided access to right dTRA and left STA, a 0.035 inch guidewire introduced to the left CCA from the contralateral dTRA was snared and externalized via left STA to improve wire support for guiding advancement. Thereafter, the left ICA lesion was successfully stented with a 7×30 mm self-expanding stent via right dTRA. All vessels involved were patent at 6-month follow-up. CONCLUSION: The STA may be a promising adjunctive access site to increase transradial catheter support for CAS or neurointerventional procedures in the anterior circulation. CLINICAL IMPACT: Transradial cerebrovascular interventions have been gaining popularity, however, unstable catheter access to distal cerebrovascular structures limits its widespread use. Guidewire externalization technique via additional STA access may improve transradial catheter stabilty and increase procedural success with possibly low access stie complication rate.

HCN channels at the cell soma ensure the rapid electrical reactivity of fast-spiking interneurons in human neocortex.

Accumulating evidence indicates that there are substantial species differences in the properties of mammalian neurons, yet theories on circuit activity and information processing in the human brain are based heavily on results obtained from rodents and other experimental animals. This knowledge gap may be particularly important for understanding the neocortex, the brain area responsible for the most complex neuronal operations and showing the greatest evolutionary divergence. Here, we examined differences in the electrophysiological properties of human and mouse fast-spiking GABAergic basket cells, among the most abundant inhibitory interneurons in cortex. Analyses of membrane potential responses to current input, pharmacologically isolated somatic leak currents, isolated soma outside-out patch recordings, and immunohistochemical staining revealed that human neocortical basket cells abundantly express hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel isoforms HCN1 and HCN2 at the cell soma membrane, whereas these channels are sparse at the rodent basket cell soma membrane. Antagonist experiments showed that HCN channels in human neurons contribute to the resting membrane potential and cell excitability at the cell soma, accelerate somatic membrane potential kinetics, and shorten the lag between excitatory postsynaptic potentials and action potential generation. These effects are important because the soma of human fast-spiking neurons without HCN channels exhibit low persistent ion leak and slow membrane potential kinetics, compared with mouse fast-spiking neurons. HCN channels speed up human cell membrane potential kinetics and help attain an input-output rate close to that of rodent cells. Computational modeling demonstrated that HCN channel activity at the human fast-spiking cell soma membrane is sufficient to accelerate the input-output function as observed in cell recordings. Thus, human and mouse fast-spiking neurons exhibit functionally significant differences in ion channel composition at the cell soma membrane to set the speed and fidelity of their input-output function. These HCN channels ensure fast electrical reactivity of fast-spiking cells in human neocortex.

Predicting the true extent of glioblastoma based on probabilistic tractography.

Glioblastoma is the most frequent type of primary brain tumors. Despite the advanced therapy, most of the patients die within 2 years after the diagnosis. The tumor has a typical appearance on MRI: a central hypointensity surrounded by an inhomogeneous, ring-shaped contrast enhancement along its border. Too small to be recognized by MRI, detached individual tumor cells migrate along white matter fiber tracts several centimeters away from the edge of the tumor. Usually these cells are the source of tumor recurrence. If the infiltrated brain areas could be identified, longer survival time could be achieved through supratotal resection and individually planned radiation therapy. Probabilistic tractography is an advanced imaging method that can potentially be used to identify infiltrated pathways, thus the real extent of the glioblastoma. Our study consisted of twenty high grade glioma patients. Probabilistic tractography was started from the tumor. The location of tumor recurrence on follow-up MRI was considered as the primary infiltrated white matter tracts. The results of probabilistic tractography were evaluated at thirteen different thresholds. The overlap with the tumor recurrence of each threshold level was then defined to calculate the sensitivity and specificity. In the group level, sensitivity (81%) and specificity (90%) were the most reliable at 5% threshold level. There were two outliers in the study group, both with high specificity and very low sensitivity. According to our results, probabilistic tractography can help to define the true extent of the glioblastoma at the time of diagnosis with high sensitivity and specificity. Individually planned surgery and irradiation could provide a better chance of survival in these patients.

Localization of macroscopically undetectable intramedullary hematoma by intraoperative epidural motor evoked potential.

Introduction: Intramedullary hematoma is an uncommon, serious neurological disease, representing a diagnostic challenge. The preferred treatment is surgical. In most of the cases the lesion can be identified macroscopically. Otherwise, finding the optimal place to perform myelotomy is demanding. Intraoperative neurophysiological monitoring plays an important role in preventing surgical complications, but its versatility for localization has not been studied so far. Case report: The present case report describes a 17-year-old patient with flaccid right inferior monoparesis (later paraparesis), ipsilateral loss of proprioception and vibration sense, contralateral analgesia below the T10 dermatome level and urinary retention (Brown-Séquard syndrome). The MRI revealed an intramedullary hematoma at the level of T8-T9 vertebral bodies. Digital subtraction angiography did not identify any vascular malformation. Urgent surgical intervention was performed. In order to prevent any complication somatosensory-evoked potential (SSEP), transcranial and epidural motor-evoked potential (tcMEP, eMEP) recordings were planned. SSEP in response to right tibial nerve stimulation and tcMEP were absent bilaterally. From electrophysiological point of view, the eMEP revealed a total conduction block of the corticospinal tract. In the absence of typical macroscopic signs (discoloration, swelling, abnormal vascularization etc.), the small intramedullary hematoma could not be identified. Therefore, it was decided to adopt eMEP technique for mapping and localizing the conduction block intraoperatively by changing the distance between the two electrodes used for recording. The hematoma was precisely localized and successfully evacuated. Postoperatively, a slow but continuous improvement was noted. Conclusion: Intraoperative neurophysiological monitoring has been suggested to play crucial role in spinal cord surgery. To our knowledge, this is the first case report using eMEP recording for guiding and localizing of an intramedullary hematoma. Beside the clear limitations of our study, it could result in a novel application of the aforementioned monitoring technique.

Automatic deep learning-driven label-free image-guided patch clamp system.

Patch clamp recording of neurons is a labor-intensive and time-consuming procedure. Here, we demonstrate a tool that fully automatically performs electrophysiological recordings in label-free tissue slices. The automation covers the detection of cells in label-free images, calibration of the micropipette movement, approach to the cell with the pipette, formation of the whole-cell configuration, and recording. The cell detection is based on deep learning. The model is trained on a new image database of neurons in unlabeled brain tissue slices. The pipette tip detection and approaching phase use image analysis techniques for precise movements. High-quality measurements are performed on hundreds of human and rodent neurons. We also demonstrate that further molecular and anatomical analysis can be performed on the recorded cells. The software has a diary module that automatically logs patch clamp events. Our tool can multiply the number of daily measurements to help brain research.

Combined Simultaneous Multiportal Approach via Minimally Invasive Transciliary and Endoscopic Endonasal Approaches for Tumors Invading Both the Skull Base and the Sinonasal Area.

BACKGROUND: A combined transcranial and transfacial approach has long been the gold standard for surgical management of large tumors with sinonasal and skull base involvement. The extended endoscopic endonasal approach for such pathologies has its advantages, but it has flaws as well, such as anatomic limitations and more ponderous skull base reconstruction and thus higher risk of postoperative complications. Our primary technique for surgical treatment of these pathologies has been a combination of transfacial and minimally invasive transciliary supraorbital keyhole approaches. With the aim to further minimize invasiveness, potential complications, and unsatisfactory aesthetic outcomes during surgical treatment of large tumors invading both the sinonasal area and the skull base, we abandoned the transfacial approach and simultaneously combined the transciliary supraorbital keyhole approach with the endoscopic endonasal approach. METHODS: The well-known microscope-assisted minimally invasive approach via a transciliary supraorbital keyhole craniotomy was combined with the endoscopic endonasal approach. RESULTS: Six patients with different histologic types of tumors affecting the sinonasal area and the skull base were operated on. The mean operative time was 3 hours, there were no unexpected intraoperative or postoperative complications, and total tumor removal was achieved in each patient. None of the patients experienced complications associated with the surgery during follow-up. CONCLUSIONS: Our combined simultaneous multiportal approach enables total tumor eradication with reduced operative time and is associated with minimal intraoperative and postoperative complications, low mortality rate, and excellent cosmetic results.

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours.

The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were re-irradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm3, and the mean planning target volume (PTV) was 316 cm3, to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.

Adaptive Radiotherapy for Glioblastoma Multiforme - The Impact on Disease Outcome.

BACKGROUND/AIM: To study the changes of glioblastoma multiforme during chemoradiotherapy (CRT) and to evaluate the impact of changes on dosimetry and clinical outcomes. PATIENTS AND METHODS: Forty-three patients underwent volumetric imaging-based replanning. Prognostic factors and gross tumor volume changes in relation to overall survival and the effect of adaptive replanning were statistically analyzed. RESULTS: Patients with total tumor removal, with shorter time to CRT (<27 days), with methylated O-6 methylguanine DNA methyltransferase and good performance status (>60%) had better survival. Tumor shrinkage in 24 patients resulted in improved survival compared to 19 in whom tumor was unchanged or progressed (25.3 vs. 11.1 months, p=0.04). Adapted planning target volume allowed a reduction in irradiated volume, while increasing survival (12.06 vs. 28.98 months, p=0.026). CONCLUSION: Tumor response during CRT has significant impact on the outcome. Adaptation of the planning target volume to the tumor changes proved to be beneficial and warrants further investigation.

[Early experiences in surgical treatment of thoracic disc herniation from posterior transdural approach at Neurosurgery Clinic Szeged University]. / A thoracalis porckorong-sérvesedés hátsó transduralis feltárása során nyert korai tapasztalatok a Szegedi Tudományegyetem, Idegsebészeti Klinikán.

Background - Because of the rare occurrence of thoracic disc herniation and surgery needed treatment the used approaches and their efficiency are still subjects of discussions. In Hungarian practice, the most frequent explorations are costotransversectomy and laminectomy, but there are many other important methods available like thoracoscopic and posterior transdural approaches. This case report will present the benefits and the surgical procedure of posterior transdural sequesterectomy, carry out for the first time in Hungary at the Neurosurgical Department on Szeged University. Case presentation - A 50-year-old female patient with achondroplasic nanism has been operated several times since 2011. She suffered from a progressive, multi-segment affected degenerative discopathy and myelopathy. Finally in the background of the recurrent paraparesis was confirmed thoracic disc herniations at the levels of T8 and T9. The use of intraoperative electrophysiology was not feasable, because the earlier described cervical myelopathy. For this reason we used the posterior transdural approach, as the best and safest, visual control warranted technique. Conclusions - The posterior transdural approach offers an alternative option for experienced surgeons, furthermore in contrast with traditional, technically difficult to implement or special instrumentation demanding approaches this technique seems to be more efficient.

An Unusual Case (Metastatic-Like Lesion) of Septic Cerebral Embolus Caused by Corynebacterium mucifaciens in a Diabetic Patient.

Septic cerebral emboli can be a challenging diagnosis to give, especially if atypical bacterial infections are the cause of it. Correct diagnosis of this condition can change the management route of the patient and result in a nonsurgical treatment. To our best knowledge, this is the first case of septic cerebral embolus caused by Corynebacterium mucifaciens reported. In this study, a 65-year-old diabetic patient who have developed ketoacidosis and went into coma was investigated for a case of septic cerebral embolization. The patient developed a sudden right-sided hemiparesis, and the radiological findings showed a tumor-like lesion on the left hemisphere at the level of the internal capsule. At first glance, presence of a metastatic tumor could not be excluded; therefore, further laboratory tests and examinations were done to rule out metastatic lesions. The blood culture of the patient revealed a case of bacteremia caused by Corynebacterium mucifaciens and then a septic cerebral embolus was suspected, but due to the rarity of this pathogen causing such complications as well as the similarity of the lesion to a metastatic brain tumor, a biopsy was performed and the histopathological findings confirmed the diagnosis of a septic cerebral embolus. Corynebacterium mucifaciens should be considered a human pathogen in immunocompromised patients and it can cause cerebral septic embolization. Metastatic brain tumors and tuberculomas should be excluded; if the uncertainty of a metastatic tumor remains, biopsy can be performed and histological findings can amplify the diagnosis of septic cerebral embolus.

Robust perisomatic GABAergic self-innervation inhibits basket cells in the human and mouse supragranular neocortex.

Inhibitory autapses are self-innervating synaptic connections in GABAergic interneurons in the brain. Autapses in neocortical layers have not been systematically investigated, and their function in different mammalian species and specific interneuron types is poorly known. We investigated GABAergic parvalbumin-expressing basket cells (pvBCs) in layer 2/3 (L2/3) in human neocortical tissue resected in deep-brain surgery, and in mice as control. Most pvBCs showed robust GABAAR-mediated self-innervation in both species, but autapses were rare in nonfast-spiking GABAergic interneurons. Light- and electron microscopy analyses revealed pvBC axons innervating their own soma and proximal dendrites. GABAergic self-inhibition conductance was similar in human and mouse pvBCs and comparable to that of synapses from pvBCs to other L2/3 neurons. Autaptic conductance prolonged somatic inhibition in pvBCs after a spike and inhibited repetitive firing. Perisomatic autaptic inhibition is common in both human and mouse pvBCs of supragranular neocortex, where they efficiently control discharge of the pvBCs.

Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of Brain Metastases.

Our retrospective analysis aimed to evaluate the clinical value of dose intensification schemes: WBRT and consecutive, delayed, or simultaneous integrated boost (SIB) in brain metastasis (BM) management. Clinical data and overall survival (OS) of 468 patients with BM from various primaries treated with 10 × 3 Gy WBRT (n = 195), WBRT+ 10 × 2 Gy boost (n = 125), or simultaneously 15 × 2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically analysed. Significant difference in OS could be detected with additional boost to WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung cancer and melanoma and both for oligo- and multiplex lesions. The OS was prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose, 4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p < 0.0001) in the class RPA 3 respectively. The significant difference in OS was also achieved with SIB. The shortened overall treatment time of SIB with lower WBRT fraction dose exhibited survival benefit over WBRT alone, and could be applied for patients developing BM even with unfavourable prognostic factors. These results warrant for further study of this approach with dose escalation using the lately available solutions for hippocampus sparing and fractionated stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction dose and boost proved to be advantageous prolonging the OS with shortened treatment time and reduced probability for cognitive decline development even for patients with poor performance status and progressing extracranial disease.