Polish cross-cultural adaptation of a disease-specific quality-of-life instrument: The Penn Acoustic Neuroma Quality-of-Life Scale.

BACKGROUND: The medical community has shown a growing interest in developing methods for measuring and comparing objective patient outcomes coupled with subjective patient assessments. Questionnaires enable healthcare professionals to obtain the patient's perspective about their experienced vestibular schwannomas (VS) symptoms quickly. To date, in Poland, a cross-cultural adapted version of a disease-specific questionnaire for the measurement of quality of life (QoL) in patients with VS has not been produced. OBJECTIVES: This study aimed to adapt the questionnaire evaluating disease-specific QoL in patients with VS (Penn Acoustic Neuroma Quality-of-Life Scale; PANQOL) to Polish and evaluate its psychometric properties. MATERIAL AND METHODS: One-hundred twenty-four patients aged between 24 and 85 years (mean (M) = 60.17 ±standard deviation (SD) = 13.27) diagnosed with VS and treated with Gamma Knife were included in the study. We used a questionnaire translated from English into Polish by a bilingual professional, verified through a back-translation. The final version consisted of 26 items. The internal consistency of the Polish version of the PANQOL scale domains was measured using the Cronbach's alpha (α). To verify the validity of PANQOL subscales, a correlation analysis was conducted between the domains of PANQOL and other questionnaires, including the Assessment of Quality of Life (AQoL-8D), the Glasgow Benefit Inventory (GBI), the 5 Well-Being Index (WHO-5), the Skarzynski Tinnitus Scale (STS) for the presence of dizziness, and the Gardner-Robertson classes. RESULTS: The majority of PANQOL domains showed excellent or good internal consistency (for a PANQOL total of 0.934; for subscales in the range of 0.916-0.424). Our analysis showed strong correlations between the total PANQOL score and AQoL-8D utility score, as well as between the subscales. We observed weak to moderately significant relationships between GBI and PANQOL domains (r = 0.18-0.43), the WHO-5 (r = 0.18-0.56) and the STS scale (r = -0.40- -0.19). CONCLUSIONS: The results demonstrated that the POL-PANQOL is a reliable and valid questionnaire for measuring QoL.

Subtotal resection of vestibular schwannoma with subsequent Gamma Knife irradiation - tumor growth control, facial and cochlear nerve outcome - preliminary results.

<b>Introduction:</b> The choice of treatment of vestibular schwannoma (VS) depends on several factors, including the tumor size, the patient's age and overall health, and the presence and severity of symptoms.<b>Aim:</b> The aim of the study was to assess the effectiveness of intentional subtotal resection (STR) of tumor followed by Gamma Knife surgery (GKS) in patients with larger VS (Koos 3 and 4).<b>Materials and methods:</b> The retrospective analysis was performed on 18 patients. Data of VS volumes measured in MRI, the facial nerve function assessed in the House-Brackmann scoring system (HB), and the results of audiological examination expressed on the Gardner-Robertson scale (GR) were collected preoperatively, postoperatively, and post-GKS.<b>Results:</b> Preoperatively, the main symptom was hearing loss observed in 13 out of 18 patients. The facial nerve function was assessed as HB 1 in 16, whereas HB 2 in 2 patients. The mean volume of the tumor in the initial MRI amounted to 16.81 cm³ . Postoperatively, the facial nerve was assessed as HB 1 or 2 in 16, whereas HB 3 in 2 patients. Serviceable hearing was presented by only 4 persons. The Mean diameter of the tumor after subtotal surgery amounted to 3.16 cm³ , 1.83 cm³ after GKS, and 1.58 cm³ at the last follow-up. The facial nerve function and hearing level remained the same as before GKS in all patients.<b>Conclusions:</b> STR followed by GKS can be a safe and effective method of treatment of large VS concerning the functional outcome of the facial nerve and the tumor volume growth control.

Planned Subtotal Resection following Stereotactic Radiosurgery of Koos 3 and 4 Vestibular Schwannomas.

Background/Objectives: Surgical resection of medium to large vestibular schwannomas (VSs, Koos grade 3 and 4) is a widely used approach, although stereotactic radiosurgery (SRS) is increasingly proposed as initial treatment. The quality of life-centered approach is challenged in cases where tumor growth control cannot be achieved with SRS, thus necessitating salvage surgery. We present a series of eight consecutive patients who required surgery due to continued tumor growth after SRS. Methods: Of the 146 patients with VS grades 3 and 4 initially treated with SRS, only eight patients (mean age, 54 ± 7.2 years; range, 42-63 years) required subsequent surgery. Their mean tumor volume was 9.9 ± 3.2 cm3. The mean time from SRS to first tumor progression and planned subtotal resection was 23 ± 5.9 months and 45 ± 17.5 months, respectively. SRS was not performed after the surgery in favor of a "wait and rescan" approach. Tumor residue was monitored on follow-up magnetic resonance imaging. In all patients, tumor growth control after planned subtotal resection was maintained at 63 ± 19.8 months. Results: None of the 146 patients had serious complications after SRS. In the eight patients who required surgery, tumor growth between 22% and 212% (mean, 4 cm3) was reported within 26 to 84 months after SRS. Before salvage surgery, they scored 1 point on the House-Brackmann scale. Subtotal excision was performed, and VIIth nerve function was preserved in all patients. At 63 ± 19.8 months, 3 patients had a House-Brackmann score of 1, four patients had a score of 2, and one patient had a score of 3. Conclusions: Surgical excision of medium to large VS after SRS can be relatively safe, provided that a quality of life-centered approach of subtotal resection is used.

Polish cross-cultural adaptation of the Glasgow Benefit Inventory as an instrument for the post-intervention measurement of change after Gamma Knife treatment.

<b>Introduction:</b> The Glasgow Benefit Inventory (GBI) is one of questionnaires for the measurement of treatment success, which is widely used in patients after vestibular schwannoma treatment.<b>Aim:</b> This study aimed to adapt the GBI originally written in English to Polish conditions and to evaluate its psychometric properties.<b>Material and methods:</b> The Polish version of the GBI used in this study was prepared by a bilingual translator, and its accuracy was ensured by back-translation. To identify the structure of the Polish version of the GBI, exploratory factor analysis was performed. The reliability was determined using Cronbach's α. To verify the validity, correlation analysis was conducted between the domains of GBI and other questionnaires.<b>Results:</b> The results of confirmatory factor analysis indicated that the original 3-factor model is not a good fit for the data. The exploratory factor analysis was performed and identified 4 factors. The total variance of the 4-factor solution was 66.25%. The Cronbach's α calculated for the total GBI reached 0.91. Our analysis confirmed significant weak or moderate correlations between tools for the measurement of general QoL (AQoL-8D: r = 0.411; p = 0.000) and health-related QoL (PANQOL: r = 0.367; p = 0.000; a tool dedicated for patients with VS), well-being (WHO-5: r = 0.432; p = 0.000), hearing and tinnitus (STS: r = -0.217; p = 0.016).<b>Conclusions:</b> This study reports the first adaptation of the GBI for patients with VS to Polish conditions. The results demonstrated that the Polish version of the GBI is a reliable and valid questionnaire that can be used to measure treatment success.

Unilateral gamma knife thalamotomy for tremor safety and efficacy in multimodal assessment: a prospective case-control study with two-year follow-up.

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. RESULTS: No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. CONCLUSIONS: UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

Fracture of the Lumbar Spine Associated with Ureteral Injury Mimicking Spondylodiscitis Followed by Cervical Spine Fracture in Patient with Ankylosing Hyperostosis.

The purpose of this case report is to describe the case of a patient with ankylosing spinal hyperostosis (ASH) and lumbar spine fracture complicated by ureteral injury mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation followed by the cervical spine fracture. A consecutive analysis and summary of the medical history, radiological documentation, operative procedure, complications, and outcomes were performed. A 59-year-old man presented with abdominal pain three weeks after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the L3/L4 level and features of ASH. Additionally, MRI scans demonstrated hyperintense fluid collection within L3/L4 intervertebral space communicating with both psoas major muscles, mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation. An in situ instrumented lumbar fusion at the L2-L3-L5-S1 levels with implantation vertebral body replacement implant at the L3/L4 level was performed. Postoperative CT imaging revealed evidence of post-traumatic right ureteral injury. Following urological treatment covering nephrectomy and ureter ligation, the patient was maintained at a 2-year follow-up. After this period, the patient presented again with tetraparesis after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the C5/C6 level. The combined anterior and posterior osteosynthesis at the C4-C5-C6-C7 levels was performed. This case report presents the rare clinical constellation regarding the lumbar spine fracture complicated by ureteral injury followed by a cervical spine fracture regarding the same patient. The potential injury of retroperitoneal structures, including the ureter after hyperextensive lumbar spine fracture, should be considered in ASH patients. In this case, one should be aware of the atypical clinical presentation regarding the observed spondylodiscitis- and osteomyelitis-like features.

Targeted sequencing of cancer-related genes reveals a recurrent TOP2A variant which affects DNA binding and coincides with global transcriptional changes in glioblastoma.

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.

Outcomes and Prognostic Factors in the Treatment of Intracanalicular Vestibular Schwannomas Using Gamma Knife Stereotactic Radiation.

BACKGROUND: No gold standard has been developed for the therapy of intracanalicular vestibular schwannomas (IVS). Options for treatment include a conservative approach, microsurgery, or radiosurgery. Although the efficacy of these treatment has been well-documented, little is known about the determinants of outcome in IVSs following radiosurgery. Therefore, we examined the results in relation to age, gender, tumor volume, distance to fundus, microcyst existence, and radiosensitivity in this group. In addition, we investigated possible predictors of facial nerve function and hearing preservation. METHODS: Ninety-four patients with unilateral IVS were included in the evaluation (52 women and 42 males). The patients were separated into younger and older age groups based on their median age (55 years). The median IVS volume was 138 mm3, microcysts were identified in 16 tumors, and 63 tumors were adjacent to the fundus. The data were analyzed using Statistica software package ver. 13.3. RESULTS: At final follow-up, a statistically significant decrease in tumor volume and no statistically significant decline in hearing were noted, but no differences between age groups were found. The sex had no effect on overall tumor growth control, facial nerve preservation, or hearing preservation. Localization of IVS close to the fundus and the presence of tumor microcysts had no effect on the control of tumor growth, preservation of hearing, and sparing of facial nerve following radiosurgery. Cochlear dose had no influence on hearing preservation. Higher tumor volume was associated with its pseudoprogression during early follow-up and a greater risk of hearing loss. CONCLUSIONS: Age, sex, tumor volume, proximity to the fundus, and the existence of a microcyst were not predictive of radiosensitivity nor preservation of facial nerve function and hearing, based on the findings. There was no effect of cochlear dose on hearing. Initial greater tumor volume was associated with an increased probability of tumor pseudoprogression.

Clinical Characteristics and Predictors of Long-Term Prognosis of Acute Peripheral Arterial Ischemia Patients Treated Surgically.

BACKGROUND: Acute peripheral arterial ischemia is a rapidly developing loss of perfusion, resulting in ischemic clinical manifestations. This study aimed to assess the incidence of cardiovascular mortality in patients with acute peripheral arterial ischemia and either atrial fibrillation (AF) or sinus rhythm (SR). METHODS: This observational study involved patients with acute peripheral ischemia treated surgically. Patients were followed-up to assess cardiovascular mortality and its predictors. RESULTS: The study group included 200 patients with acute peripheral arterial ischemia and either AF (n = 67) or SR (n = 133). No cardiovascular mortality differences between the AF and SR groups were observed. AF patients who died of cardiovascular causes had a higher prevalence of peripheral arterial disease (58.3% vs. 31.6%, p = 0.048) and hypercholesterolemia (31.2% vs. 5.3%, p = 0.028) than those who did not die of such causes. Patients with SR who died of cardiovascular causes more frequently had a GFR <60 mL/min/1.73 m2 (47.8% vs. 25.0%, p = 0.03) and were older than those with SR who did not die of such causes. The multivariable analysis shows that hyperlipidemia reduced the risk of cardiovascular mortality in patients with AF, whereas in patients with SR, an age of ≥75 years was the predisposing factor for such mortality. CONCLUSIONS: Cardiovascular mortality of patients with acute ischemia did not differ between patients with AF and SR. Hyperlipidemia reduced the risk of cardiovascular mortality in patients with AF, whereas in patients with SR, an age of ≥75 years was a predisposing factor for such mortality.

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS: MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10µL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 µg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.

The S-100B level, intracranial pressure, body temperature, and transcranial blood flow velocities predict the outcome of the treatment of severe brain injury.

This study evaluates the applicability of S100B levels, mean maximum velocity (Vmean) over time, pulsatility index (PI), intracranial pressure (ICP), and body temperature (T) for the prediction of the treatment of patients with traumatic brain injury (TBI). Sixty patients defined by the Glasgow Coma Scale score ≤ 8 were stratified using the Glasgow Coma Scale into 2 groups: favorable (FG: Glasgow Outcome Scale ≥ 4) and unfavorable (UG: Glasgow Outcome Scale < 4). The S100B concentration was at the time of hospital admission. Vmean was measured using transcranial Doppler. PI was derived from a transcranial Doppler examination. T was measured in the temporal artery. The differences in mean between FG and UG were tested using a bootstrap test of 10,000 repetitions with replacement. Changes in S100B, Vmean, PI, ICP, and T levels stratified by the group were calculated using the one-way aligned rank transform for nonparametric factorial analysis of variance. The reference ranges for the levels of S100B, Vmean, and PI were 0.05 to 0.23 µg/L, 30.8 to 73.17 cm/s, and 0.62 to 1.13, respectively. Both groups were defined by an increase in Vmean, a decrease in S100B, PI, and ICP levels; and a virtually constant T. The unfavorable outcome is defined by significantly higher levels of all parameters, except T. A favorable outcome is defined by S100B < 3 mg/L, PI < 2.86, ICP > 25 mm Hg, and Vmean > 40 cm/s. The relationships provided may serve as indicators of the results of the TBI treatment.

Tumor control and hearing preservation after radiosurgery of intracanalicular vestibular schwannomas - systematic review.

Intracanalicular vestibular schwannomas (IVS) account for 8% of all vestibular schwannomas and their detection is still increasing due to high availability of magnetic resonance (MRI). Radiosurgery is one of several commonly acceptable methods of IVS treatment, but some risk may still exist with that treatment. The aim of this study is to analyze the clinical outcomes in tumor control and hearing preservation after radiosurgery of IVS. The retrospective analysis included 14 scientific papers available in the PubMed database. Assessment of tumor volume was performed based on gadolinium-enhanced T1-weighted scans. Hearing preservation was assessed using the Gardner-Robertson classification (GR class). Statistical analysis was performed using IBM SPSS Statistics 27. It was revealed that tumor growth control in IVS treated with radiosurgery was higher than in the wait-and-see strategy. The hearing preservation was similar in patients after wait and see and the surgical group. Radiosurgery was associated with low risk of facial nerve dysfunction.

Prognostic properties of the association between the S-100B protein levels and the mean cerebral blood flow velocity in patients diagnosed with severe traumatic brain injury.

Craniocerebral injury (CBI) is tissue damage caused by a sudden mechanical force. CBI can result in neurological, neuropsychological and psychiatric dysfunctions. Currently, the severity of CBI is assessed using the Glasgow Coma Scale, brain perfusion pressure measurements, transcranial Doppler tests and biochemical markers. This study aimed to determine the applicability of the S-100B protein levels and the time-averaged mean maximum cerebral blood flow velocity (Vmean) as a means of predicting the treatment outcomes of CBI in the first 4 days of hospitalization. The results validated the standard reference ranges previously proposed for the concentration of S-100B (0.05-0.23 µg/l) and the mean of cerebral blood flow velocity (30.9 to 74.1 cm/sec). The following stratification scheme was used to predict the success of treatment: Patients with a Glasgow Outcome Scale (GOS) score ≥4 or GOS <4 were stratified into 'favorable' and 'unfavorable' groups, respectively. The favorable group showed relatively constant levels of the S-100B protein close to the normal range and exhibited an increase in Vmean, but this was still within the normal range. The unfavorable group exhibited a high level of S-100B protein and increased Vmean outside of the normal ranges. The changes in the levels of S-100B in the unfavorable and favorable groups were -0.03 and -0.006 mg/l/h, respectively. Furthermore, the rate of decrease in the Vmean value in the unfavorable and favorable groups were -0.26 and -0.18 cm/sec/h, respectively. This study showed that constant levels of S-100B protein, even slightly above the normal range, associated with an increase in Vmean was indicative of a positive therapeutic outcome. However, additional research is required to obtain the appropriate statistical strength required for clinical practice.

Usability of the Level of the S100B Protein, the Gosling Pulsatility Index, and the Jugular Venous Oxygen Saturation for the Prediction of Mortality and Morbidity in Patients with Severe Traumatic Brain Injury.

The high frequency of traumatic brain injury imposes severe economic stress on health and insurance services. The objective of this study was to analyze the association between the serum S100B protein, the Gosling pulsatility index (PI), and the level of oxygen saturation at the tip of the internal jugular vein (SjVO2%) in patients diagnosed with severe TBI. The severity of TBI was assessed by a GCS score ≤ 8 stratified by Glasgow outcome scale (GOS) measured on the day of discharge from the hospital. Two groups were included: GOS < 4 (unfavorable group (UG)) and GOS ≥ 4 (favorable group (UG)). S100B levels were higher in the UG than in the FG. PI levels in the UG were also substantially higher than in the FG. There were similar levels of SjVO2 in the two groups. This study confirmed that serum S100B levels were higher in patients with unfavorable outcomes than in those with favorable outcomes. Moreover, a clear demarcation in PI between unfavorable and FGs was observed. This report shows that mortality and morbidity rates in patients with traumatic brain injury can be assessed within the first 4 days of hospitalization using the S100B protein, PI values, and SjVO2.

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). PATIENTS AND METHODS: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. RESULTS: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007). CONCLUSIONS: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.

Use of a novel ball-joint guide array for magnetic resonance imaging-guided cannula placement and convective delivery: technical note.

OBJECTIVE: The objective of this study was to assess the feasibility, accuracy, effectiveness, and safety of an MRI-compatible frameless stereotactic ball-joint guide array (BJGA) as a platform for cannula placement and convection-enhanced delivery (CED). METHODS: The authors analyzed the clinical and imaging data from consecutive patients with aromatic l-amino acid decarboxylase (AADC) deficiency who underwent infusion of adeno-associated virus (AAV) containing the AADC gene (AAV2-AADC). RESULTS: Eleven patients (7 females, 4 males) underwent bilateral MRI-guided BJGA cannula placement and CED of AAV2-AADC (22 brainstem infusions). The mean age at infusion was 10.5 ± 5.2 years (range 4-19 years). MRI allowed for accurate real-time planning, confirmed precise cannula placement after single-pass placement, and permitted on-the-fly adjustment. Overall, the mean bilateral depth to the target was 137.0 ± 5.2 mm (range 124.0-145.5 mm). The mean bilateral depth error was 0.9 ± 0.7 mm (range 0-2.2 mm), and the bilateral radial error was 0.9 ± 0.6 mm (range 0.1-2.3 mm). The bilateral absolute tip error was 1.4 ± 0.8 mm (range 0.4-3.0 mm). Target depth and absolute tip error were not correlated (Pearson product-moment correlation coefficient, r = 0.01). CONCLUSIONS: Use of the BJGA is feasible, accurate, effective, and safe for cannula placement, infusion MRI monitoring, and cannula adjustment during CED. The low-profile universal applicability of the BJGA streamlines and facilitates MRI-guided CED.

Current strategies for the treatment of malignant gliomas - experience of the Department of Neurosurgery, Brodno Masovian Hospital in Warsaw.

INTRODUCTION: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. MATERIAL AND METHODS: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management - from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. RESULTS: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. DISCUSSION: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.

Direct convective delivery of adeno-associated virus gene therapy for treatment of neurological disorders.

Molecular biological insights have led to a fundamental understanding of the underlying genomic mechanisms of nervous system disease. These findings have resulted in the identification of therapeutic genes that can be packaged in viral capsids for the treatment of a variety of neurological conditions, including neurodegenerative, metabolic, and enzyme deficiency disorders. Recent data have demonstrated that gene-carrying viral vectors (most often adeno-associated viruses) can be effectively distributed by convection-enhanced delivery (CED) in a safe, reliable, targeted, and homogeneous manner across the blood-brain barrier. Critically, these vectors can be monitored using real-time MRI of a co-infused surrogate tracer to accurately predict vector distribution and transgene expression at the perfused site. The unique properties of CED of adeno-associated virus vectors allow for cell-specific transgene manipulation of the infused anatomical site and/or widespread interconnected sites via antero- and/or retrograde transport. The authors review the convective properties of viral vectors, associated technology, and clinical applications.

Advancing gene therapies, methods, and technologies for Parkinson's Disease and other neurological disorders.

INTRODUCTION: Vector-based intracerebral gene therapies are being used to treat specific neurodegenerative conditions such as Parkinson's Disease (PD). This review presents a basis for central nervous system (CNS) gene therapy treatments of neurodegenerative diseases such as PD, as well as the need for novel skill sets and health delivery strategies within the clinical neurosciences (neurology and neurosurgery) to meet future demand for such therapies. STATE OF THE ART: Preclinical vector-based gene therapy approaches have been translated into clinical trials for PD and other neurodegenerative conditions. Unfortunately, such trials, and parallel efforts using other therapeutics, have yet to provide a breakthrough. Image-guided convection enhanced delivery (CED) optimises the parenchymal distribution of gene therapies applied within the CNS, and may ultimately provide such a breakthrough. CLINICAL IMPLICATIONS: Currently, image-guided CED and gene therapy are not part of training programmes for most neurosurgeons and neurologists. As a result, few medical centres and hospitals have sufficiently experienced teams to participate in gene transfer clinical trials for PD or other neurological conditions. If CNS gene therapies prove to be efficacious for PD and/or other conditions, the demand for such treatments will overwhelm the available number of experienced clinical neuroscience teams and treatment centres. FUTURE DIRECTIONS: Expanded indications and demand for CNS gene therapies will require a worldwide educational effort to supplement the training of clinical neuroscience practitioners. Initially, a limited number of Centres of Excellence will need to establish relevant educational training requirements and best practice for such therapeutic approaches. Advanced technologies, including robotics and artificial intelligence, are especially germane in this regard, and will expand the treatment team's capabilities while assisting in the safe and timely care of those afflicted.