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.

FORAMEN OVALE AND FORAMEN ROTUNDUM: CHARACTERIZATION OF POSTNATAL DEVELOPMENT.

The sphenoid bone development occurs in both prenatal and postnatal periods. Sphenoid bone openings are used as surgical landmarks and are of great importance for neurosurgeons in everyday practice. The aim of this study was to identify morphological characteristics, postnatal development and remodeling, as well as clinical aspect of the sphenoid bone openings and to investigate their relationship and difference in size. The macerated sphenoid bones analyzed in this study were scanned by micro-computed tomography. Areas and distance in-between foramen ovale and foramen rotundum were measured. In addition, different shapes of foramen ovale were described. The most common shape of foramen ovale on both sides was oval, followed by the round, almond and elongated shapes. Modest to strong positive correlations between all foramina and age for the whole sample and both subsamples were presented, except for the right foramen rotundum area in the male subsample, which did not show significant correlation with age. Our study revealed changes in postnatal development and anatomy of foramen ovale and foramen rotundum, primarily in the aspects of size and shape, and should contribute to reducing the risk of damage to neurovascular structures during surgical procedures.

T2-Fluid-Attenuated Inversion Recovery Mismatch Sign in Grade II and III Gliomas: Is There a Coexisting T2-Diffusion-Weighted Imaging Mismatch?

OBJECTIVE: To determine whether the T2 fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign in diffuse gliomas is associated with an equivalent pattern of disparity in signal intensities when comparing T2- and diffusion-weighted imaging (DWI). METHODS: The level of correspondence between T2-FLAIR and T2-DWI evaluations in 34 World Health Organization grade II/III gliomas and interreader agreement among 3 neuroradiologists were assessed by calculating intraclass correlation coefficient and κ statistics, respectively. Tumoral apparent diffusion coefficient values were compared using t test. RESULTS: There was an almost perfect correspondence between the 2 mismatch signs (intraclass correlation coefficient = 0.824 [95% confidence interval, 0.68-0.91]) that were associated with higher mean tumoral apparent diffusion coefficient (P < 0.01). Interreader agreement was substantial for T2-FLAIR (Fleiss κ = 0.724) and moderate for T2-DWI comparisons (Fleiss κ = 0.589) (P < 0.001). CONCLUSIONS: The T2-FLAIR mismatch sign is usually reflected by a distinct microstructural pattern on DWI. The management of this tumor subtype may benefit from specifically tailored imaging assessments.

The Stereological Analysis and Spatial Distribution of Neurons in the Human Subthalamic Nucleus.

The subthalamic nucleus (STN) is a small, ovoid structure, and an important site of deep brain stimulation (DBS) for the treatment of Parkinson's disease. Although the STN is a clinically important structure, there are many unresolved issues with regard to it. These issues are especially related to the anatomical subdivision, neuronal phenotype, neuronal composition, and spatial distribution. In this study, we have examined the expression pattern of 8 neuronal markers [nNOS, NeuN, parvalbumin (PV), calbindin (CB), calretinin (CR), FOXP2, NKX2.1, and PAX6] in the adult human STN. All of the examined markers, except CB, were present in the STN. To determine the neuronal density, we have performed stereological analysis on Nissl-stained and immunohistochemical slides of positive markers. The stereology data were also used to develop a three-dimensional map of the spatial distribution of neurons within the STN. The nNOS population exhibited the largest neuronal density. The estimated total number of nNOS STN neurons is 281,308 ± 38,967 (± 13.85%). The STN neuronal subpopulations can be divided into two groups: one with a neuronal density of approximately 3,300 neurons/mm3 and the other with a neuronal density of approximately 2,200 neurons/mm3. The largest density of STN neurons was observed along the ventromedial border of the STN and the density gradually decreased toward the dorsolateral border. In this study, we have demonstrated the presence of 7 neuronal markers in the STN, three of which were not previously described in the human STN. The human STN is a collection of diverse, intermixed neuronal subpopulations, and our data, as far as the cytoarchitectonics is concerned, did not support the tripartite STN subdivision.

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.

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.

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.

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.

HbA1c in patients with intracranial meningiomas WHO grades I and II: A preliminary study.

Meningiomas are among the most common primary brain tumors. There is a growing need for novel ways of differentiating between benign (World Health Organization [WHO] grade I) and atypical (WHO grade II) meningiomas as well as for novel markers of the tumor's future behavior. A difference between glucose metabolism in atypical and benign meningiomas is well known. However, a significant correlation between the systemic metabolic status of the patient and the meningioma WHO grade has not yet been established. Our aim was to compare the WHO grades of intracranial meningiomas with the patient's HbA1c levels as a more reliable marker of the chronic systemic metabolic status than the fasting blood glucose value, which is usually looked at. We retrospectively analyzed 15 patients and compared their meningioma WHO grade with their preoperative HbA1c values. Our results show that patients with benign intracranial meningiomas have significantly lower HbA1c value. Conversely, patients with atypical intracranial meningiomas have higher HbA1c values. Furthermore, we showed that the proliferation factor Ki67 was statistically strongly correlated with the HbA1c value (p < .001. These results imply a possible positive correlation between meningioma cell proliferation and the chronic systemic glycemia. Further research in this area could not only lead to better understanding of meningiomas but could have significant clinical application.

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.

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.

Conus Medullaris Arteriovenous Malformation Presenting with Acute Dysphagia and Intractable Hiccups.

BACKGROUND: Conus medullaris arteriovenous malformations (AVMs) are rare spinal vascular malformations presenting most frequently with features of myelopathy (Foix-Alajounine syndrome), radiculopathy, bowel/bladder dysfunction, or acute spinal hemorrhage (Coup de poignard of Michon) causing profound neurological deficit. Here we present the case of a young patient with progressive dysphagia and intractable hiccups as a rare first presentation symptom of later verified conus medullaris AVM. CASE DESCRIPTION: A 21-year-old male patient presented with acute onset of dysphagia and persistent hiccups. His magnetic resonance imaging of the spine demonstrated a lesion at the T11 and T12 levels with an associated holocord syrinx and syringobulbia to the level of the medulla. The patient underwent a decompressive suboccipital craniectomy and C1 (atlas) laminectomy with wide myelotomy of the medulla followed by T11 and T12 laminectomy and AVM reduction. Two days after partial AVM occlusion the patient developed transient worsening of his symptoms. Repeat magnetic resonance imaging showed recurrence of dilatation of the central canal. A syringo-subarachnoid shunt was sited at the level of the previous myelotomy of the medulla, after which his neurological symptoms resolved completely. CONCLUSIONS: This is the first case report in the English literature to date of a conus AVM presenting with intractable hiccups. These are extremely rare sporadic vascular malformations, and although their natural history is poorly understood, symptomatic patients generally deteriorate, culminating in severe disability. Management requires a multimodality approach including combined endovascular and microsurgical treatment. The patient in our case made a full recovery confirmed at 2-year follow-up.

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.

Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state: experience in 14 patients.

OBJECTIVE An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS) caused by hypoxic encephalopathy or traumatic brain injury (TBI) is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei has been attempted as a therapeutic procedure mainly in patients with TBI. The purpose of this study was to investigate the therapeutic use of DBS for patients in VS or MCS. METHODS Fourteen of 49 patients in VS or MCS qualified for inclusion in this study and underwent DBS. Of these 14 patients, 4 were in MCS and 10 were in VS. The etiology of VS or MCS was TBI in 4 cases and hypoxic encephalopathy due to cardiac arrest in 10. The selection criteria for DBS, evaluating the status of the cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation, and the results of positron emission tomography (PET) and MRI examinations. The target for DBS was the centromedian-parafascicular (CM-pf) complex. The duration of follow-up ranged from 38 to 60 months. RESULTS Two MCS patients regained consciousness and regained their ability to walk, speak fluently, and live independently. One MCS patient reached the level of consciousness, but was still in a wheelchair at the time the article was written. One VS patient (who had suffered a cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died of respiratory infection, sepsis, or cerebrovascular insult (1 of each). The other 7 patients remained without substantial improvement of consciousness. CONCLUSIONS Spontaneous recovery from MCS/VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare. Therefore, if a patient in VS or MCS fulfills the selection criteria (presence of somatosensory evoked potentials from upper extremities, motor and brainstem auditory evoked potentials, with cerebral glucose metabolism affected not more than the level of hypometabolism, which is judged using PET), DBS could be a treatment option.