Follow-up of intra-arterial delivery of bevacizumab for treatment of butterfly glioblastoma in patient with first-in-human, real-time MRI-guided intra-arterial neurointervention.

This case report shows that real-time MRI may aid in the precision of intra-arterial delivery of bevacizumab to butterfly glioblastoma. Fast clinical improvement, decrease of contrast enhancing status, and no serious adverse effects were observed at discharge from hospital. The patient regained pre-recurrent neurological status for 2 months with a subsequent fast clinical decline and an increase in tumor volume. The patient underwent a second procedure of intra-arterial delivery of bevacizumab to the brain, with substantial clinical and radiological improvement, but not the level of improvement observed after the first procedure. Another clinical decline occurred with an increase in tumor size and the patient was treated 2 months later with a third intra-arterial infusion of bevacizumab. While another positive effect was achieved, it was less pronounced than before, and the patient died 1.5 months later. There were no technical, ischemic or other complications during the procedures. The patient survived 218 days from the first symptoms of tumor recurrence, 190 days from the first MRI, and 175 days from the first intra-arterial treatment of bevacizumab.

Acute platelet response to aneurysmal subarachnoid hemorrhage depends on severity and distribution of bleeding: an observational cohort study.

Microthrombosis after aneurysmal subarachnoid hemorrhage (aSAH) is considered to initiate neuroinflammation, vessel remodeling, and blood-brain barrier leakage. We aimed to verify the hypothesis that the intensity of thrombogenicity immediately after aSAH depends on the amount and distribution of extravasated blood. This observational cohort study included 37 consecutive aSAH patients admitted no longer than 24 h after ictus. Volumes of subarachnoid and intraventricular hemorrhages as well as the Subarachnoid Hemorrhage Early Brain Edema Scale (SEBES) score were calculated in each case. Platelet system status was described by platelet count (PLT), mean platelet volume (MPV), MPV to PLT ratio, and platelet-large cell ratio (P-LCR). Median hemorrhage volume amounted to 11.4 ml (interquartile range 2.8-26.8 ml). Patients with more severe hemorrhage had lower PLT and higher MPV to PLT ratio (ρ = - 0.49, p < .002; ρ = 0.50, p < .002, respectively). PLT decreased by 2.80 G/l per 1 ml of hemorrhage volume (95% CL 1.30-4.30, p < .001). Further analysis revealed that intraventricular hemorrhage volume was associated with P-LCR and MPV (ρ = 0.34, p < .039; ρ = 0.33, p < .048, respectively), whereas SAH volume with PLT and MPV:PLT ratio (ρ = - 0.40, p < .013; ρ = 0.41, p < .013, respectively). The odds of unfavorable neurological outcome increased 3.95 times per 1 fl of MPV (95% CI 1.19-13.12, p < .025). MPV was independently correlated with SEBES (ρ = 0.44, p < .006). This study demonstrated that the extent and distribution of aneurysmal subarachnoid hemorrhage are related to different types of acute platelet response, which may be interpreted as local and systemic thrombogenicity. Increased mean platelet volume measured in the acute phase of aSAH may identify patients at risk for unfavorable neurological outcomes and may serve as a marker of early brain injury.

Clipping of a ruptured middle cerebral artery aneurysm in a patient with coronavirus disease 2019 (COVID-19): A case report.

AIM OF THE STUDY: The aim of this study is to present our suggestions for organization, personal protective equipment (PPE) use, work flow of the operating theater, and the treatment of patients with COVID-19 and co-existing neurological disease. MATERIALS AND METHODS: We present the case of a 70-year-old male who was transferred to our Department because of subarachnoid hemorrhage with ruptured right middle cerebral artery aneurysm and SARS CoV-2 infection. The emergency clipping of the aneurysm and hematoma evacuation was performed. According to the therapeutic committee guidelines, chloroquine was started for COVID-19 treatment. RESULTS: Postoperatively, the patient is in good condition, with the Glasgow Coma Scale (GCS) score of 15, with mild, left hemiparesis, 4+/5 points on the Lovett scale, without symptoms of acute respiratory distress syndrome (ARDS). No one from the stuff was infected during the treatment. CONCLUSIONS: Managing patients with infectious diseases such as COVID-19 presents many challenges and risks for healthcare personnel. Our experience suggests that by following strict safety protocols of PPE use, donning and doffing, and reducing operation time, the surgery may be safe for both the healthcare personnel and the patient.

Republished: Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note.

Patients suffering from malignant brain tumors are burdened with a grim prognosis. The blood brain barrier is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has been recently shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma perfused and facilitates predictable drug targeting. Moreover, PET imaging has revealed that IA, not intravenous, delivery of bevacizumab results in brain accumulation, providing strong rationale for utilizing the IA route. Here, we present our experience in a patient with recurrent butterfly glioblastoma enrolled in first-in-man MRI-guided neurointervention for targeted IA drug delivery.

Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note.

Patients with malignant brain tumors have a poor prognosis. The blood-brain barrier (BBB) is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation. It has recently been shown in animal studies that MRI is superior to X-ray for guiding IA infusions, as it allows direct visualization of the brain parenchyma supplied by the catheter and facilitates predictable drug targeting. Moreover, PET imaging has shown that IA rather than intravenous delivery of bevacizumab results in accumulation in the brain, providing a strong rationale for using the IA route. We present a patient with recurrent butterfly glioblastoma enrolled in a first-in-man MRI-guided neurointervention for targeted IA drug delivery.

Langerhans cell histiocytosis of the orbit and frontal sinus of the adult woman: A first case report in Poland.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a term describing a clonal proliferation of pathologic Langerhans cells (histiocytes), which may manifest as unisystem (unifocal or multifocal) or multisystem disease. LCH is a rare cause of the orbital tumor with the predilection to its lateral wall which is particularly common in children. CASE DESCRIPTION: We report an unusual case of a 33-year-old woman, 6 months after childbirth, who presented with the edema of the right orbit and upper eyelid with headaches. On physical examination, the patient had a right superior and lateral swelling of the eyelid and the orbit and right enophthalmos, without blurred vision. Magnetic resonance imaging showed well-defined, expansile, intensely homogeneously enhancing mass lesion in the right superolateral orbital rim with the destruction of the upper wall of the orbit, growing into the frontal sinus and frontal part of the cranium with the bold of the dura mater in this region. Radical excision of the tumor was achieved through a right fronto-temporo-orbito-zygomatic craniotomy. Histopathological examination had confirmed the diagnosis of the LCH. The patient was discharged home with a modified Rankin Scale score of 0. CONCLUSION: The main purpose of this case report is that LCH should be considered as one of the possible causes of quickly appearing tumor of the orbit in adults.

Application of Neurokinin-1 Receptor in Targeted Strategies for Glioma Treatment. Part I: Synthesis and Evaluation of Substance P Fragments Labeled with 99mTc and 177Lu as Potential Receptor Radiopharmaceuticals.

Gliomas, particularly WHO grade IV glioblastoma multiforme, are one of the most common and aggressive primary tumors of the central nervous system. The neuropeptide, substance P (SP), is the physiological ligand of the neurokinin-1 (NK-1) receptor that is consistently overexpressed in glioblastoma cells. The aim of this work was to study physico-chemical and biological properties of different SP analogues labeled with technetium-99m and lutetium-177 radionuclides. The synthesized compounds were characterized in vitro by partition coefficients (logP) and their stability was investigated in various physiological solutions. Biological properties (Kd, Bmax) were characterized using the U373 MG cell line. The obtained lipophilicity values of the [99mTc]NS3/CN-SP and [177Lu]DOTA-SP radiobioconjugates were in the range of -0.3 to +0.6 and -2.5 to -5.0, respectively. The studied radiobioconjugates were stable in PBS buffer and CSF, as well as in 10 mM histidine and/or cysteine solutions whereas in human serum showed enzymatic biodegradation. [177Lu]DOTA-[Thi8,Met(O2)11]SP(1⁻11), [177Lu]DOTA-SP(4⁻11) and [177Lu]DOTA-[Thi8,Met(O2)11]SP(5⁻11) radiobioconjugates bound specifically to NK-1 receptors expressed on glioblastoma cells with affinity in the nanomolar range. To conclude, the shorter analogues of SP can be used as vectors, nevertheless they still do not fulfil all requirements for preparations in nuclear medicine.

Comparison of the timing of intervention and treatment modality of poor-grade aneurysmal subarachnoid hemorrhage.

OBJECTIVES: The timing and modality of intervention in the treatment of poor-grade aneurysmal subarachnoid haemorrhage (aSAH) has not been defined. The purpose of the study is to analyse whether early treatment and type of intervention influence the clinical outcomes of poor-grade aSAH patients. MATERIAL AND METHODS: Patients with poor-grade aSAH were retrieved. Demographics, Fisher grade, radiological characteristics and clinical outcomes were recorded. Outcomes were compared using the modified Rankin Scale (mRS), for groups treated early within 24 hours of aSAH or later and by clipping or endovascular therapy. Multivariate multiple regression model and logistic regression were used to assess factors affecting outcomes at discharge in mRS and length of stay. RESULTS: The study was conducted on 79 patients. 47 (59%) were treated by clipping, 38 (48%) received intervention within 24 hours of aSAH. Patients treated <24h had significantly lower mortality (n = 5; 13% vs. n = 14; 37%; p < .023), higher rate of 0-3 mRS (n = 22;58% vs. n = 9; 22%; p < .039) and were younger (49.5 ± 6.1 vs. 65.8 ± 7.4 years; p < .038). There were no significant differences in mRS between clipping and endovascular therapy. Predictors of length of stay were ICH, MLS, endovascular therapy, location in posterior circulation, Fisher grade and time to intervention <24h. Early intervention, <24h significantly influenced the favourable results in mRS (0-3); (OR 4,14; Cl95% 3.82-4.35). Posterior circulation aneurysms, midline shift and intracerebral hematoma were correlated with poor outcomes. CONCLUSIONS: Early treatment, within 24 h, of poor-grade aSAH confirmed better clinical outcome compared to later aneurysm securement. There was no significant difference between clipping and endovascular treatment.

Down-regulation of IKKß expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma.

Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological deficits in GBM patients are poorly understood. We analyzed immune/inflammatory gene expression in five datasets of low and high grade gliomas, and performed Gene Ontology and signaling pathway analyses to identify defective transcriptional responses. The expression of many immune/inflammatory response and TLR signaling pathway genes was reduced in high grade gliomas compared to low grade gliomas. In particular, we found the reduced expression of the IKBKB, a gene coding for IKKß, which phosphorylates IκB proteins and represents a convergence point for most signal transduction pathways leading to NFκB activation. The reduced IKBKB expression and IKKß levels in GBM tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The IKKß expression was down-regulated in microglia/macrophages infiltrating glioblastoma. NFκB activation, prominent in microglia/macrophages infiltrating low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB expression and NFκB signaling in microglia/macrophages infiltrating glioblastoma correlates with defective expression of immune/inflammatory genes and M2 polarization that may result in the global impairment of anti-tumor immune responses in glioblastoma.

Analysis of the serum components in acute period after subarachnoid hemorrhage.

AIM: Multi-profile monitoring of various blood serum factors during acute subarachnoid haemorrhage (SAH) is crucial for successful treatment. The aim of the study is to evaluate the serum concentration of different blood factors in the acute period of SAH. MATERIAL AND METHODS: 31 patients with confirmed aneurysmal SAH were enrolled in a prospective study. The concentrations of the following serum compounds were assessed on the day of admission and reassessed after 5 days: lipids profile, cardiac functionality enzymes and markers, electrolytes, osmolality, CRP (C-reactive protein), glucose, creatinine, urine. RESULTS: The mean level of high-density lipoprotein (HDL) changed significantly from 43.9±23.9 mg/dL to 27.5±19,8 mg/dL, p=0,013 (mean dif. 16.5±14,1 mg/dL; 37,3%). Concentration of low-density lipoprotein (LDL) decreased by 28.6% (mean dif. 26.78±61.32; p=0.047). Values of triglicerydes and total cholesterol did not differ significantly between the initial evaluations and these repeated after 5 days. The overall serum ions (Na < sup > + < /sup > , K < sup > + < /sup > , Mg < sup > 2+ < /sup > , Ca < sup > 2+ < /sup > ) concentrations and osmolality did not differ significantly between the initial measurements and after 5 days from SAH. The only mean value that appeared to be substantially increased at initial measurement was NT-proBNP and reached 1928.8±4952 pg/ ml, this value dropped down to 392.87±1147.9 mg/ml after 5 days (mean dif. 1535.96±4808.76 pg/ml; 79,6%; p = 0.247). CRP increased over 2 fold after 5 days up to 29.267±28.614 mg/L (mean dif. 16.06±34.05 pg/L; 121.6%; p=0.028). At 5-day follow up hematocrit dropped to 33.38 ± 3.81% from the initial value of 39.63 ± 2,56% (p=0.02). CONCLUSION: This study showed a significant decrease in the serum level of LDL and HDL, while triglycerides were moderately heightened. Routine monitoring of lipid profile and statin administration at the early stage of SAH is recommended.

Correlation between the aneurysm morphometry and severity of subarachnoid hemorrhage in the posterior cerebral circulation.

OBJECTIVE: The aim of the study was to examine the correlation between various morphometric factors of the posterior circulation aneurysms and the severity of neurologic status and radiologic extent of subarachnoid hemorrhage. METHODS: A total of 105 patients with ruptured posterior circulation aneurysms (IAs) were retrospectively analyzed in the study. The neurologic status was graded in World Federation of Neurosurgical Societies (WFNS) scale and radiological severity of subarachnoid hemorrhage was assessed in Fisher revised scale (FRS). All patients were qualified for 3-dimensional digital subtraction angiography. The following morphometric measurements were taken: dome size, dome-to-neck ratio, neck size, parent artery size; size ratio (SR), neck-to-parent artery ratio, inflow angle, and diameters of posterior circulation arteries. The univariate and the multiple regression models were used for all independent variables. The significant predictors were compared between ruptured and unruptured IAs. RESULTS: Univariate regression analysis revealed that inflow angle influenced grading in WFNS and that FRS grades were positively correlated with SR, dome-to-neck ratio, and inflow angle. The multiple regression model confirmed that inflow angle is an independent factor influencing WFNS scale. FRS is affected by 2 factors: SR and inflow angle. SR was more strongly correlated with FRS (r = 0.403) than with inflow angle (r = 284). The comparison of inflow angle and SR in ruptured and unruptured IAs showed a significant difference between means, 125.18 ± 21.86 versus 103.86 ± 17.7 degrees and 2.48 ± 0.46 versus 1.91 ± 0.45, respectively. The cut off points were 115.9 degrees for inflow angle and 2.31 for SR. CONCLUSION: Inflow angle and SR were found to be correlated with grading in FRS, and WFNS scale was correlated with inflow angle.

Aneurysms of the anterior and posterior cerebral circulation: comparison of the morphometric features.

BACKGROUND: Intracranial aneurysms (IAs) located in the posterior circulation are considered to have higher annual bleed rates than those in the anterior circulation. The aim of the study was to compare the morphometric factors differentiating between IAs located in the anterior and posterior cerebral circulation. METHODS: A total number of 254 IAs diagnosed between 2009 and 2012 were retrospectively analyzed. All patients qualified for diagnostic, three-dimensional rotational angiography. IAs were assigned to either the anterior or posterior cerebral circulation subsets for the analysis. Means were compared with a t-test. The univariate and stepwise logistic regression analyses were used to determine the predictors of morphometric differences between the groups. For the defined predictors, ROC (receiver-operating characteristic) curves and interactive dot diagrams were calculated with the cutoff values of the morphometric factors. RESULTS: The number of anterior cerebral circulation IAs was 179 (70.5 %); 141 (55.5 %) aneurysms were ruptured. Significant differences between anterior and posterior circulation IAs were found for: the parent artery size (5.08 ± 1.8 mm vs. 3.95 ± 1.5 mm; p < 0.05), size ratio (2.22 ± 0.9 vs. 3.19 ± 1.8; p < 0.045) and aspect ratio (AR) (1.91 ± 0.8 vs. 2.75 ± 1.8; p = 0.02). Predicting factors differentiating anterior and posterior circulation IAs were: the AR (OR = 2.20; 95 % CI 1.80-270; Is 270 correct or should it be 2.70 and parent artery size (OR = 0.44; 95 % CI 0.38-0.54). The cutoff point in the ROC curve was 2.185 for the AR and 4.89 mm for parent artery size. CONCLUSIONS: Aspect ratio and parent artery size were found to be predictive morphometric factors in differentiating between anterior and posterior cerebral IAs.

Four-year trends in the treatment of cerebral aneurysms in Poland in 2009-2012.

BACKGROUND: The dilemma concerning the appropriate treatment of the intracranial aneurysms (IAs) has not yet been resolved and still remains under fierce debate. This study refers to the recent trends in the use of and outcomes related to coiling compared with clipping for unruptured and ruptured IAs in Poland over a 4-year period. METHODS: The analysis refers to treatment of IAs performed in Poland between 2009-2012. Patients' records were cross-matched by ICD-9 codes for ruptured SAH (430) or unruptured cerebral aneurysm (437.3) along with codes for clipping (39.51) and coiling (39.79, 39.72, or 39.52). Multivariable logistic regression was used to compare in-hospital deaths, hospital length of stay (LOS), therapy allocation and aneurysm locations in unruptured vs. ruptured and clipped vs. coiled groups. Differences in the number of procedures between 16 administrative regions were standardized per 100,000 people. RESULTS: In 2009-2012, 11,051 procedures were identified, including 5,968 ruptured and 5,083 unruptured aneurysms. Overall increase was 2.3 % in clipping and 13.1 % in coiling; a significant trend was found in endovascular procedures (p = 0.044). Ruptured aneurysms were clipped more frequently (OR = 1.66;); in unruptured IAs, endovascular procedure was preferred 3.5 times more than clipping. The annual in-hospital mortality was 7.6 % in clipping and 6.7 % in endovascular treatment. LOS was two times longer after clipping in unruptured aneurysms (OR = 2.013). After the procedures were standardized per 100,000 people, the average for Poland was established as 9.09 in 2009, 10.86 in 2010, 10.55 in 2011, and 11.49 in 2012. This index had the highest values in Mazovia (12.9, 2009; 15.4, 2010; 17.4, 2011; 18.6, 2012. CONCLUSIONS: Data analysis revealed an increase in overall number of IAs treated in Poland between 2009-2012. A significant upward trend of endovascular procedures was found, whereas the number of clipped aneurysms remained relatively steady over the study period.

Endovascular embolization of ruptured and unruptured posterior circulation aneurysms. A multi-factor analysis.

AIM: Complete aneurysm obliteration reduces the risk of rebleeding and is an important goal of the aneurysm treatment. MATERIAL AND METHODS: A retrospective analysis of 63 patients undergoing endovascular treatment of posterior circulation aneurysms. The occlusion rate was stratified to three groups: complete, incomplete and partial. In the analysis compared the influence of the selected characteristics: age, sex, WFNS grade, aneurysm location, size of the aneurysm dome and neck, neck to dome ratio, on the effectiveness of embolization in each group. A multi-factor analysis with probit model and linear regression was applied to assess the impact of all characteristics on the complete occlusion. RESULTS: In the series of 63 single aneurysms, 51 were ruptured and 12 unruptured aneurysms. Complete occlusion was achieved in 36 (57.1%), incomplete in 15 (23.8%), partial in 12 (19%) patients. In patients with the neck size of 1-2 mm the complete occlusion was in 75% (24/32) incomplete in 12,5% (4/32), while when the neck size was 2-4 mm these rates were 38.7% (12/31) and 29% (9/31) respectively. The predictor of total occlusion in probit and linear regression model was only one independent variable, the narrow-neck size. CONCLUSION: Multi-factor analysis found that the strongest predictor of the complete occlusion is the aneurysm neck size.

Statistical analysis of the intracranial procedures in Poland in 2008-2009.

BACKGROUND AND PURPOSE: Quantitative and qualitative analysis of neurosurgical procedures provides important data for assessment of the development and trends in the field of neurosurgery. The authors present statistical data on intracranial procedures (IPs) performed in Poland in 2008-2009. MATERIAL AND METHODS: Data on IPs come from reports of the National Health Fund, grouped according to the system of Diagnosis-Related Groups, group A - nervous system diseases. Data concerning the year 2009 include all IPs performed in Poland. Data from the second half of 2008 to 2009 (18 months) come from 35 neurosurgical centers in Poland, divided by provinces. We analyzed the number of IPs, the cost of procedures, duration of hospitalization and deaths. RESULTS: 20 849 IPs were performed in Poland in 2009. The most common procedure was A12 (6807; 32.65%), and the rarest was A04 (96; 0.46%). The annual cost of all IPs was 228 599 956 PLN. Average cost of the procedure ranged from 1578 PLN (A14) to 47 940 PLN (A03). Duration of the hospitalization ranged between 3 days (A14) and 12 days (A12). The highest percentage of deaths was reported for A01 (n = 1050, 19.06%). Reports from 35 neurosurgical centers in the second half of 2008 and 2009 showed the highest number of IPs per 100 000 population in Kujawsko-Pomorskie (93) and the lowest in Wielkopolskie (27) and Podkarpackie (27). The highest number of IPs (1669) was performed in neurosurgical center M1 (Malopolskie), and the lowest (99) in W1 (Wielkopolskie). CONCLUSIONS: A significant disparity in the number of IPs performed in different centers in Poland was observed.

Itraorbital organic foreign body - radiological methods in diagnosis - case report.

Intraorbital foreign bodies, especially non-metallic ones, remain an important diagnostic and therapeutic problem. Organic foreign bodies contain large quantities of bacterial flora contributing to rapid onset of inflammation which may promptly damage the optic nerve. Further progression of inflammation may involve the structures of central nervous system. US examination is a preliminary, commonly available diagnostic method, although it is not always successful in visualizing foreign bodies. CT scan remains a standard investigation used to visualize intraorbital foreign bodies, although with organic foreign bodies, its results may be inconclusive. MRI allows for visualization and precise identification of foreign bodies, which is vital for surgery. The issue of intraorbital foreign bodies is an interdisciplinary problem requiring the co-operation between ophthalmologists and neurosurgeons.