Clinical application of the RONNA G4 system - preliminary validation of 23 robotic frameless brain biopsies.

AIMS: To report the outcomes of robot-assisted brain biopsies performed using a novel RONNA G4 system. The system was developed by a research group from the Faculty of Mechanical Engineering and Naval Architecture and a team of neurosurgeons from Dubrava University Hospital, University of Zagreb School of Medicine. METHODS: This prospective study included 49 biopsies analyzed during one year: 23 robotic frameless and 26 frame-based Leksell stereotactic biopsies. We analyzed the presenting symptoms, tumor range and location, postoperative complications, pathohistological diagnosis, diagnostic yield, as well as operation and hospitalization duration. The target point error was calculated to assess the accuracy of the RONNA system. RESULTS: No postoperative mortality, morbidity, or infections were observed. In the frameless robotic biopsy group, only one pathohistological diagnosis was inconclusive. Therefore, the diagnostic yield was 95.6% (22/23), similar to that of the framebased Leksell stereotactic biopsy group (95.1% or 25/26). The average target point error in the frameless robotic biopsy group was 2.15±1.22 mm (range 0.39-5.85). CONCLUSION: The RONNA G4 robotic system is a safe and accurate tool for brain biopsy, although further research warrants a larger patient sample, comparison with other robotic systems, and a systematic analysis of the entry and target point errors.

The vicious interplay between disrupted sleep and malignant brain tumors: a narrative review.

Malignant brain tumors are among the most aggressive human neoplasms. One of the most common and severe symptoms that patients with these malignancies experience is sleep disruption. Disrupted sleep is known to have significant systemic pro-tumor effects, both in patients with other types of cancer and those with malignant brain lesions. We therefore provide a review of the current knowledge on disrupted sleep in malignant diseases, with an emphasis on malignant brain tumors. More specifically, we review the known ways in which disrupted sleep enables further malignant progression. In the second part of the article, we also provide a theoretical framework of the reverse process. Namely, we argue that due to the several possible pathophysiological mechanisms, patients with malignant brain tumors are especially susceptible to their sleep being disrupted and compromised. Thus, we further argue that addressing the issue of disrupted sleep in patients with malignant brain tumors can, not just improve their quality of life, but also have at least some potential of actively suppressing the devastating disease, especially when other treatment modalities have been exhausted. Future research is therefore desperately needed.

Decreased brain volume may be associated with the occurrence of peri-lead edema in Parkinson's disease patients with deep brain stimulation.

BACKGROUND: Peri-lead edema (PLE) is a poorly understood complication of deep brain stimulation (DBS), which has been described in patients presenting occasionally with profound and often delayed symptoms with an incidence ranging from 0.4% up to even 100%. Therefore, our study aims to investigate the association of brain and brain compartment volumes on magnetic resonance imaging (MRI) with the occurrence of PLE in Parkinson's disease (PD) patients after DBS implantation in subthalamic nuclei (STN). METHODS: This retrospective study included 125 consecutive PD patients who underwent STN DBS at the Department of Neurosurgery, Dubrava University Hospital from 2010 to 2022. Qualitative analysis was done on postoperative MRI T2-weighted sequence by two independent observers, marking PLE on midbrain, thalamus, and subcortical levels as mild, moderate, or severe. Quantitative volumetric analysis of brain and brain compartment volumes was conducted using an automated CIVET processing pipeline on preoperative MRI T1 MPRAGE sequences. In addition, observed PLE on individual hemispheres was delineated manually and measured using Analyze 14.0 software. RESULTS: In our cohort, PLE was observed in 32.17%, mostly bilaterally. Mild PLE was observed in the majority of patients, regardless of the level observed. Age, sex, diabetes, hypertension, vascular disease, and the use of anticoagulant/antiplatelet therapy showed no significant association with the occurrence of PLE. Total grey matter volume showed a significant association with the PLE occurrence (r = -0.22, p = 0.04), as well as cortex volume (r = -0.32, p = 0.0005). Cortical volumes of hemispheres, overall hemisphere volumes, as well as hemisphere/total intracranial volume ratio showed significant association with the PLE occurrence. Furthermore, the volume of the cortex and total grey volume represent moderate indicators, while hemisphere volumes, cortical volumes of hemispheres, and hemisphere/total intracranial volume ratio represent mild to moderate indicators of possible PLE occurrence. CONCLUSION: The results of our study suggest that the morphometric MRI measurements, as a useful tool, can provide relevant information about the structural status of the brain in patients with PD and represent moderate indicators of possible PLE occurrence. Identifying patients with greater brain atrophy, especially regarding grey matter before DBS implantation, will allow us to estimate the possible postoperative symptoms and intervene in a timely manner. Further studies are needed to confirm our findings and to investigate other potential predictors and risk factors of PLE occurrence.

Bilateral posterior fossa chronic subdural hematoma as a cause of hydrocephalus.

Background: Infratentorial chronic subdural hematoma (cSDH) is still a rather elusive neurosurgical entity, which, due to its proximity and likely compression of the cerebellum and brainstem, can lead to devastating consequences. To establish standardized treatment, more studies and reports regarding its therapy are needed. We report a case of a simultaneous unilateral supratentorial and bilateral infratentorial cSDH, with the latter causing hydrocephalus and successfully treated with a bilateral burr-hole trepanation of occipital bone and placement of subdural drains. Case Description: A 71-year-old man with gait disturbance, Glasgow Coma Scale 12, and a radiologically verified unilateral supratentorial and bilateral cSDH of the posterior fossa causing cerebellum, brainstem, and fourth ventricle compression with obstructive hydrocephalus, underwent surgical evacuation of infratentorial hematoma with a bilateral burr-hole trepanation. The postoperative course was uneventful, with a control head computed tomography scan showing the resolution of the hematoma and hydrocephalus. The patient was discharged with no newly acquired neurological deficits. Conclusion: Due to a limited number of reports and studies involving infratentorial cSDHs causing hydrocephalus, decision-making and optimal surgical treatment remain unclear. We recommend a timely surgical evacuation of the hematoma if the patient is symptomatic while avoiding placement of external ventricular drainage.

Spontaneous spinal subdural hematoma in COVID-19 patient: Croatian national COVID hospital experience.

Background: Spontaneous spinal subdural hematoma (SSDH) is a rare condition and causes of acute spinal cord compression, with symptoms varying from mild to severe neurological deficit. SSDH could occur as a consequence of posttraumatic, iatrogenic, or spontaneous causes, including underlying arteriovenous malformations, tumors, or coagulation disorder. Due to its rarity, it is difficult to establish standardized treatment. We present a rare case of SSDH in COVID-19 patient and course of treatment in COVID hospital. Case Description: A 71-year-old female patient was admitted due to instability, weakness of the left leg, and intensive pain in the upper part of thoracic spine as well as mild respiratory symptoms of COVID-19. She was not on pronounced anticoagulant therapy and her coagulogram at admission was within normal range. MRI revealed acute subdural hematoma at the level C VII to Th III compressing the spinal cord. The patient underwent a decompressive Th I and Th II laminectomy and hematoma evacuation. Post-operative MRI revealed a satisfactory decompression and re-expansion of the spinal cord. COVID-19 symptoms remained mild. Conclusion: SSDH represents a neurological emergency, possibly leading to significant deficit and requires urgent recognition and treatment. One of the main difficulties when diagnosing is to consider such condition when there is no history of anticoagulant treatment or previous trauma. Since high incidence of coagulation abnormalities and thromboembolic events was described COVID-19 patients, when considering the pathology of the central nervous system, the bleeding within it due to COVID-19 should be taken into account, in both brain and spine.

Frameless stereotactic brain biopsy and external ventricular drainage placement using the RONNA G4 system.

Robot-assisted stereotactic procedures are among the latest technological improvements in neurosurgery. Herein, to the best of our knowledge, we report a first external ventricular drainage (EVD) placement using the RONNA G4 robotic system preformed together with brain biopsy, all in one procedure. A patient was presented with progressive drowsiness, cognitive slowing, poor mobility and incontinent. Magnetic resonance imaging brain scans revealed multicentric process located in the basal ganglia right with extensive vasogenic edema and dilatated ventricular system. Using the RONNAplan software two trajectories were planned: one for brain biopsy on the left side and one for EVD implantation on the right side; the procedures went without complications. The RONNA G4 robotic system is an accurate neurosurgical tool for performing frameless brain biopsies and EVD placement. Further studies are needed in order to enroll a larger patient sample and to calculate the possible placement deviation, and to perform the comparison with other robotic systems.

Glycemia and venous thromboembolism in patients with primary brain tumors - A speculative review.

Venous thromboembolism (VTE) is a significant public health issue causing severe morbidity and mortality. One of the most vulnerable populations for VTE development are cancer patients. And among them, patients with brain tumors have arguably the highest risk of developing this often fatal complication. Hyperglycemia is a well-known factor which leads to a wide variety of pro-thrombotic changes. In this article, we review the current literature on the topic of VTE in brain tumor patients. We also discuss the known correlation between VTE and glycemia, as well as the importance and frequency of glycemia dysregulation in brain tumor patients. Based on the already well-known importance of glucose metabolism in cancer patients, as well as the previous research of our group, we hypothesize that there is a significant number of brain tumor patients who have chronically elevated glycemia, a fact that so-far hasn't been reported. We argue that these patients carry a significantly higher risk of VTE development and would benefit greatly from strict glycemic control. We present our hypothesis, the ways in which to test it, as well as the possible counter-arguments against it. Our hope is that other investigators will be inspired by our article to continue this type of research, since we consider the topic of VTE in brain tumor patients highly important and urgent, primarily due to its prevalence and severity.

Structural changes in brains of patients with disorders of consciousness treated with deep brain stimulation.

Disorders of consciousness (DOC) are one of the major consequences after anoxic or traumatic brain injury. So far, several studies have described the regaining of consciousness in DOC patients using deep brain stimulation (DBS). However, these studies often lack detailed data on the structural and functional cerebral changes after such treatment. The aim of this study was to conduct a volumetric analysis of specific cortical and subcortical structures to determine the impact of DBS after functional recovery of DOC patients. Five DOC patients underwent unilateral DBS electrode implantation into the centromedian parafascicular complex of the thalamic intralaminar nuclei. Consciousness recovery was confirmed using the Rappaport Disability Rating and the Coma/Near Coma scale. Brain MRI volumetric measurements were done prior to the procedure, then approximately a year after, and finally 7 years after the implementation of the electrode. The volumetric analysis included changes in regional cortical volumes and thickness, as well as in subcortical structures. Limbic cortices (parahippocampal and cingulate gyrus) and paralimbic cortices (insula) regions showed a significant volume increase and presented a trend of regional cortical thickness increase 1 and 7 years after DBS. The volumes of related subcortical structures, namely the caudate, the hippocampus as well as the amygdala, were significantly increased 1 and 7 years after DBS, while the putamen and nucleus accumbens presented with volume increase. Volume increase after DBS could be a result of direct DBS effects, or a result of functional recovery. Our findings are in accordance with the results of very few human studies connecting DBS and brain volume increase. Which mechanisms are behind the observed brain changes and whether structural changes are caused by consciousness recovery or DBS in patients with DOC is still a matter of debate.

The Accuracy of Direct Targeting Using Fusion of MR and CT Imaging for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Parkinson's Disease.

INTRODUCTION: In 33 consecutive patients with Parkinson's disease (PD) undergoing awake deep brain stimulation (DBS) without microelectrode recording (MER), we assessed and validated the precision and accuracy of direct targeting of the subthalamic nucleus (STN) using preoperative magnetic resonance imaging (MRI) and stereotactic computed tomography (CT) image fusion combined with immediate postoperative stereotactic CT and postoperative MRI, and we report on the side effects and clinical results up to 6 months' follow-up. MATERIALS AND METHODS: Preoperative nonstereotactic MRI and stereotactic CT images were merged and used for planning the trajectory and final lead position. Immediate postoperative stereotactic CT and postoperative nonstereotactic MRI provided the validation of the final electrode position. Changes in the Unified Parkinson's Disease Rating Scale III (UPDRS III) scores and the levodopa equivalent daily doses (LEDD) and appearance of adverse side effects were assessed. RESULTS: The mean Euclidian distance (ED) error between the planned position and the final position of the lead in the left STN was 1.69 ± 0.82 mm and that in the right STN was 2.12 ± 1.00. The individual differences between planned and final position in each of the three coordinates were less than 2 mm. The UPDRS III scores improved by 75% and LEDD decreased by 45%. Few patients experienced complications, such as postoperative infection (n = 1), or unwanted side effects, such as emotional instability (n = 1). CONCLUSION: Our results confirm that direct targeting of an STN on stereotactic CT merged with MRI could be a valid method for placement the DBS electrode. The magnitude of our targeting error is comparable with the reported errors when using MER and other direct targeting approaches.

Frameless stereotactic brain biopsy: A prospective study on robot-assisted brain biopsies performed on 32 patients by using the RONNA G4 system.

BACKGROUND: We present a novel robotic neuronavigation system (RONNA G4), used for precise preoperative planning and frameless neuronavigation, developed by a research group from the University of Zagreb and neurosurgeons from the University Hospital Dubrava, Zagreb, Croatia. The aim of study is to provide comprehensive error measurement analysis of the system used for the brain biopsy. METHODS: Frameless stereotactic robot-assisted biopsies were performed on 32 consecutive patients. Post-operative CT and MRI scans were assessed to precisely measure and calculate target point error (TPE) and entry point error (EPE). RESULTS: The application accuracy of the RONNA system for TPE was 1.95 ± 1.11 mm, while for EPE was 1.42 ± 0.74 mm. The total diagnostic yield was 96.87%. Linear regression showed statistical significance between the TPE and EPE, and the angle of the trajectory on the bone. CONCLUSION: The RONNA G4 robotic system is a precise and highly accurate autonomous neurosurgical assistant for performing frameless brain biopsies.

Stereotactic Neuro-Navigation Phantom Designs: A Systematic Review.

Diverse stereotactic neuro-navigation systems are used daily in neurosurgery and novel systems are continuously being developed. Prior to clinical implementation of new surgical tools, methods or instruments, in vitro experiments on phantoms should be conducted. A stereotactic neuro-navigation phantom denotes a rigid or deformable structure resembling the cranium with the intracranial area. The use of phantoms is essential for the testing of complete procedures and their workflows, as well as for the final validation of the application accuracy. The aim of this study is to provide a systematic review of stereotactic neuro-navigation phantom designs, to identify their most relevant features, and to identify methodologies for measuring the target point error, the entry point error, and the angular error (α). The literature on phantom designs used for evaluating the accuracy of stereotactic neuro-navigation systems, i.e., robotic navigation systems, stereotactic frames, frameless navigation systems, and aiming devices, was searched. Eligible articles among the articles written in English in the period 2000-2020 were identified through the electronic databases PubMed, IEEE, Web of Science, and Scopus. The majority of phantom designs presented in those articles provide a suitable methodology for measuring the target point error, while there is a lack of objective measurements of the entry point error and angular error. We identified the need for a universal phantom design, which would be compatible with most common imaging techniques (e.g., computed tomography and magnetic resonance imaging) and suitable for simultaneous measurement of the target point, entry point, and angular errors.

A biphasic tumor in posterior cranial fossa and the pineal region in young adult.

BACKGROUND: Biphasic tumors of the central nervous system are rarely described and mainly consisted out of the glial and mesenchymal component. The tumor originated out of both astrocytes and pinealocytes, best to our knowledge, has not been described. We present a case of a brain tumor consisted out of pilocytic astrocytoma (PA) and pineocytoma as components situated in the pineal region and posterior cranial fossa in young adult. CASE DESCRIPTION: We present a 21-year-old patient with a history of intermittent headache, followed by nausea and vomiting, double vision, and dextropulsion. Magnetic resonance imaging revealed an extensive cystic-solid expansive formation in the posterior cranial fossa with a solid part in the area of the pineal gland. The patient underwent surgical resection. The pathohistological analysis showed two types of tumor cells; the major part of tumor showed features of PA, while minor part corresponded to pineocytoma. CONCLUSION: PA accounts for 5% of all gliomas and is most common in children and young adults. It usually occurs in the cerebellum, the optic pathway, third ventricular region, etc. Pineocytomas are rare, accounting up to 1% of all intracranial tumors. Since tumors origin is different, there must be complex molecular events or mutations that can lead to cell rearrangements and generation of two histologically different tissues in the same tumor mass. The course of treatment options is different for PA and pineocytoma; therefore, the case of brain mass consisted out of two different tissues can be helpful when deciding about the treatment of tumors in posterior cranial fossa and pineal region.

The Dubrava Model-A Novel Approach in Treating Acutely Neurotraumatized Patients in Rural Areas: A Proposal for Management.

Introduction Neurotrauma is one of the leading causes of death and disabilities nowadays and represents one of the largest socioeconomic problems in rich countries, as well as developing ones. A satisfying, medically viable, and cost-effective model of managing acutely neurotraumatized patients, especially ones who come from distant and/or rural areas, has yet to be found. Patient outcome after acute neurotrauma depends on many factors of which the possibility of urgent treatment by an experienced specialist team has a crucial role. Here, we present our own way of managing acutely neurotraumatized patients from distant places which is unique in Croatia, the Dubrava model. Methods We present our 5-year experience cooperating with general hospitals in four neighboring cities (Cakovec, Bjelovar, Sisak, and Koprivnica) in managing, operating, and taking care of acutely neurotraumatized patients. Results More than 300 surgeries have been performed in these hospitals through the Dubrava model. Our experience so far provides encouraging results that this system could also be successfully implemented in other institutions. Furthermore, we recorded an increased number of surgeries each year, as well as a good mutual cooperation with the local general hospitals. Discussion This trauma managing model is one of a kind in Croatia. We argue that it is not only better for the patients, providing them with better chances of survival, and disability-free recovery, but is also far superior in many ways to the dominant and currently prevalent way of treating these patients in other parts of Croatia. Conclusion The Dubrava model of treating patients in rural and distant areas is a reliable and proven model with many benefits and as such its implementation should be considered in other institutions as well.

Intracranial Mature Teratoma in an Adult Patient: A Case Report.

Introduction : Primary intracranial teratoma is a subtype of germ cell tumors, classified into three subtypes. They occur very rarely, with only several reported individual cases in adults. Case Description We present a patient with an intermittent headache in the right frontal region. Magnetic resonance imaging (MRI) revealed a right sided high frontal parasagittal mass that compressed the falx, the right lateral ventricle, as well as the brain parenchyma. Patient underwent surgical treatment. Histopathological analysis described mature teratoma. Four months after the surgical treatment there were no signs of residual intracranial mass or relapse. Discussion Primary intracranial teratoma in adults has a nonspecific clinical presentation. MRI reveals a solitary irregular mass with multilocularity and mixed signals derived from different tissues. The patients age, biochemical markers, and patohistological analysis are necessary to confirm the diagnosis. Conclusion Teratoma treatment strategy still remains controversial. It includes radical resection whenever possible. Since the residual portion of mature teratoma may contain part of immature or malignant tissue, tumor recurrence after surgical removal is possible. Also, new tumor mass could occur at other sites intracranial after the initial one was removed. Thus, although patients usually recover, they should be followed-up for a long period of time.

Brain biopsy performed with the RONNA G3 system: a case study on using a novel robotic navigation device for stereotactic neurosurgery.

BACKGROUND: Robotic neuronavigation is becoming an important tool for neurosurgeons. We present a case study of a frameless stereotactic biopsy guided by the RONNA G3 robotic neuronavigation system. METHODS: A 45 year-old patient with a history of vertigo, nausea and vomiting was diagnosed with multiple periventricular lesions. Neurological status was unremarkable. A frameless robotic biopsy of a brain lesion was performed. RESULTS: Three tissue samples were obtained. There were no intraoperative or postoperative complications. Histological analysis showed a B-cell lymphoma. After merging the preoperative CT scan with the postoperative MRI and CT scans, the measured error between the planned and the postoperatively measured entry point was 2.24 mm and the measured error between the planned and postoperatively measured target point was 2.33 mm. CONCLUSIONS: The RONNA G3 robotic system was used to navigate a Sedan brain biopsy needle to take tissue samples and could be a safe and precise tool for brain biopsy.

Intraspinal calcinosis mimicking intervertebral disc extrusion: A clinical and surgical case report.

BACKGROUND: Subcutaneous calcinosis is a well-recognized manifestation of systemic sclerosis that usually involves multiple pressure points and may also be found in the paraspinal or intraspinal regions. In this case, intraspinal calcinosis uniquely led to a severe neurological deficit. CASE DESCRIPTION: A patient with severe systemic sclerosis/calcinosis exhibited left greater than right lower extremity radiculopathy attributed to intraspinal left-sided L4-L5 calcinosis. On examination, the patient exhibited bilateral positive Lasegue signs, distal lower extremity weakness (left greater than right), and bilaterally decreased Achilles responses. When the magnetic resonance imaging (MRI) revealed a significant intracanalicular mass on the left side at the L4-L5 level, the patient underwent a left-sided L4-L5 decompressive laminectomy. The MRI scan 5 years later revealed no recurrence of the calcinosis, and the patient had no residual neurological deficit. CONCLUSIONS: Spinal calcinosis rarely involves the lumbar spinal canal. Here, a patient with a large left-sided L4-L5 focus of intraspinal calcinosis, mimicking a disc herniation, required a laminectomy to resect the lesion. Lumbar calcinosis should be radiologically evaluated utilizing using X-ray, MRI, and computed tomography studies to adequately document the pathology. Patients, when symptomatic, may require surgical decompression and excision of these lesions.

Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.

INTRODUCTION: Primary central nervous system lymphoma and its subtype, primary dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the central nervous system without any dissemination. They are extremely rare cases of extra nodal lymphomas accounting for 1--5% of intracranial tumors. CASE REPORT: We present a patient diagnosed with primary dural lymphoma in right frontal brain region who underwent surgical resection. Histopathological analysis revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative, no signs of newly onset infiltration were present. DISCUSSION: Primary dural lymphoma most likely presents with unusual radiological signs, which can easily be mistaken for meningioma, the main differential diagnosis. A thorough immunological, histopathological and clinical patients profile should be conducted in order to establish the certainty of diagnosis. Although there are few treatment options: surgery, radiotherapy or chemotherapy, there is no established treatment protocol.