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.

Deep brain stimulation in disorders of consciousness: 10 years of a single center experience.

Disorders of consciousness (DoC), namely unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), represent severe conditions with significant consequences for patients and their families. Several studies have reported the regaining of consciousness in such patients using deep brain stimulation (DBS) of subcortical structures or brainstem nuclei. Our study aims to present the 10 years' experience of a single center using DBS as a therapy on a cohort of patients with DoC. Eighty Three consecutive patients were evaluated between 2011 and 2022; entry criteria consisted of neurophysiological and neurological evaluations and neuroimaging examinations. Out of 83, 36 patients were considered candidates for DBS implantation, and 32 patients were implanted: 27 patients had UWS, and five had MCS. The stimulation target was the centromedian-parafascicular complex in the left hemisphere in hypoxic brain lesion or the one better preserved in patients with traumatic brain injury. The level of consciousness was improved in seven patients. Three out of five MCS patients emerged to full awareness, with the ability to interact and communicate. Two of them can live largely independently. Four out of 27 UWS patients showed consciousness improvement with two patients emerging to full awareness, and the other two reaching MCS. In patients with DoC lasting longer than 12 months following traumatic brain injury or 6 months following anoxic-ischemic brain lesion, spontaneous recovery is rare. Thus, DBS of certain thalamic nuclei could be recommended as a treatment option for patients who meet neurological, neurophysiological and neuroimaging criteria, especially in earlier phases, before occurrence of irreversible musculoskeletal changes. Furthermore, we emphasize the importance of cooperation between centers worldwide in studies on the potentials of DBS in treating patients with DoC.

Predictive value of spinal CSF volume in the preoperative assessment of patients with idiopathic normal-pressure hydrocephalus.

Introduction: The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment. Materials and methods: In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test. Results: Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (n = 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml; n = 7). Discussion: This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.

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.

Cerebrospinal fluid micro-volume changes inside the spinal space affect intracranial pressure in different body positions of animals and phantom.

Interpersonal differences can be observed in the human cerebrospinal fluid pressure (CSFP) in the cranium in an upright body position, varying from positive to subatmospheric values. So far, these changes have been explained by the Monroe-Kellie doctrine according to which CSFP should increase or decrease if a change in at least one of the three intracranial volumes (brain, blood, and CSF) occurs. According to our hypothesis, changes in intracranial CSFP can occur without a change in the volume of intracranial fluids. To test this hypothesis, we alternately added and removed 100 or 200 µl of fluid from the spinal CSF space of four anesthetized cats and from a phantom which, by its dimensions and biophysical characteristics, imitates the cat cerebrospinal system, subsequently comparing CSFP changes in the cranium and spinal space in both horizontal and vertical positions. The phantom was made from a rigid "cranial" part with unchangeable volume, while the "spinal" part was made of elastic material whose modulus of elasticity was in the same order of magnitude as those of spinal dura. When a fluid volume (CSF or artificial CSF) was removed from the spinal space, both lumbar and cranial CSFP pressures decreased by 2.0-2.5 cm H2O for every extracted 100 µL. On the other hand, adding fluid volume to spinal space causes an increase in both lumbar and cranial CSFP pressures of 2.6-3.0 cm H2O for every added 100 µL. Results observed in cats and phantoms did not differ significantly. The presented results on cats and a phantom suggest that changes in the spinal CSF volume significantly affect the intracranial CSFP, but regardless of whether we added or removed the CSF volume, the hydrostatic pressure difference between the measuring sites (lateral ventricle and lumbar subarachnoid space) was always constant. These results suggest that intracranial CSFP can be increased or decreased without significant changes in the volume of intracranial fluids and that intracranial CSFP changes in accordance with the law of fluid mechanics.

Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis.

The extracellular matrix (ECM) is an important regulator of excitability and synaptic plasticity, especially in its highly condensed form, the perineuronal nets (PNN). In patients with drug-resistant mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis type 1 (HS1) is the most common histopathological finding. This study aimed to evaluate the ECM profile of HS1 in surgically treated drug-resistant patients with MTLE in correlation to clinical findings. Hippocampal sections were immunohistochemically stained for aggrecan, neurocan, versican, chondroitin-sulfate (CS56), fibronectin, Wisteria floribunda agglutinin (WFA), a nuclear neuronal marker (NeuN), parvalbumin (PV), and glial-fibrillary-acidic-protein (GFAP). In HS1, besides the reduced number of neurons and astrogliosis, we found a significantly changed expression pattern of versican, neurocan, aggrecan, WFA-specific glycosylation, and a reduced number of PNNs. Patients with a lower number of epileptic episodes had a less intense diffuse WFA staining in Cornu Ammonis (CA) fields. Our findings suggest that PNN reduction, changed ECM protein, and glycosylation expression pattern in HS1 might be involved in the pathogenesis and persistence of drug-resistant MTLE by contributing to the increase of CA pyramidal neurons' excitability. This research corroborates the validity of ECM molecules and their modulators as a potential target for the development of new therapeutic approaches to drug-resistant epilepsy.

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.

TRANSVENOUS APPROACH FOR INDIRECT CAROTID-CAVERNOUS FISTULA USING DETACHABLE COILS: A CASE REPORT AND REVIEW OF TREATMENT OPTIONS.

Carotid-cavernous fistula (CCF) is a relatively rare pathology with a low incidence compared with other vascular pathologies. They can be classified based on hemodynamics as low- or high-flow fistulas, and anatomically as direct or indirect fistulas. Anatomy of the shunt somewhat dictates the selection of endovascular treatment, meaning the venous or arterial approach and selection of embolizing materials. Although there is general agreement as to when to access CCF transvenously or transarterialy, which depends on the shunt being direct or indirect, there is no uniform agreement on which occlusion method should be used. Herein, we report a case of an 80-year-old woman treated for indirect CCF using detachable coils. We also provide a brief review of the literature, including recent advances in treatment of said entities. In conclusion, selection of both the approach and material used depends on the operator's experience and preference.

METEOROLOGICAL VARIABLES ASSOCIATED WITH SUBARACHNOID HEMORRHAGE: A SINGLE CENTER STUDY.

Spontaneous subarachnoid hemorrhage (SAH) can occur unexpectedly and independently of the classic risk factors. Several different factors could affect intracranial aneurysm (IA) rupture, such as morphological and hemodynamic factors. The aim of this study was to establish the potential association of meteorological data such as temperature, atmospheric pressure, and humidity, and the onset of clinical symptoms preceding hospital admission of patients with acute SAH due to IA rupture. This retrospective study included 130 consecutive patients admitted for non-traumatic SAH with a determinable onset of SAH symptoms. The effects of meteorological parameters of atmospheric pressure, ambient temperature, and relative air humidity on the day of acute SAH onset and 24 hours prior to the onset of symptoms were recorded and analyzed in each patient. Spearman rank correlation analysis was used to assess the risks of incident SAH on the basis of daily meteorological data. Seasonal incidence of acute SAH showed the peak incidence in winter and a trough in summer, with monthly incidence peak in January and December. The circadian rhythm analysis showed the peak incidence of SAH in the forenoon, followed by the evening. Acute SAH incidence showed moderate positive association with daily atmospheric pressure (p<0.05), while no association was found with ambient temperature and relative air humidity. Our results suggested no significant association of changes in ambient temperature and relative humidity with the risk of SAH. Increases in atmospheric pressure were weakly associated with a higher SAH risk. Additional studies are needed to establish in detail both meteorological and morphological factors important to predict IA rupture and SAH.

Decoding the Role of DVL1 in Intracranial Meningioma.

In the search for molecular candidates for targeted meningioma therapies, increasing attention has been paid to the role of signaling pathways in the development and progression of intracranial meningiomas. Although it is well known that the Wnt signaling pathway is involved in meningioma progression, the role of its central mediator, DVL1, is still unclear. In order to investigate the influence of DVL1 gene alterations on the progression of human intracranial meningioma, we focused on its central PDZ domain, which is responsible for DVL interaction with the Fzd receptor and the phosphorylation of DVL mediated through the casein kinases CK1 and CK2. A genetic analysis of genomic instability revealed the existence of microsatellite instability in 9.09% and the loss of heterozygosity in 6.06% of the samples. The sequencing of the PDZ gene region showed repetitive deletions of two bases located in intron 7 and exon 8, and a duplication in intron 8 in most samples, with different outcomes on the biological function of the DVL1 protein. Immunohistochemistry revealed that the nuclear expression of DVL1 was significantly correlated with a higher expression of active ß-catenin (p = 0.029) and a higher meningioma grade (p = 0.030), which leads to the conclusion that it could be used as biomarker for meningioma progression and the activation of the Wnt signaling pathway.

Malignant transformation of pleomorphic xanthoastrocytoma in pregnant patient: Clinical case and ethical dilemma.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor, accounting for <1% of astrocytic tumors. Due to its rarity, etiology, natural history, and biologic behavior is not completely explained. We present a case of malignant transformation of a PXA to glioblastoma in pregnant patient 6 month after tumor biopsy. CASE DESCRIPTION: A 28-year-old female patient was presented with a newly onset of headache, nausea, and right-sided hemiparesis at 21st week of pregnancy. Magnetic resonance imaging (MRI) revealed cystic mass in the left frontal region. Patient underwent biopsy to confirm pathohistological analysis; the tumor tissue corresponded to an anaplastic PXA. Two weeks after initial biopsy, open surgery along with gross total tumor removal was performed confirming pathohistological analysis. Six months later, after childbirth, and control MRI revealed a recurrent tumor mass: the patient underwent surgical resection and the tumor tissue corresponded to a glioblastoma. The patients were further treated with radiation and chemotherapy according to oncologist. CONCLUSION: Distinguishing between PXA patients who have a good prognosis and those at risk for early progression is very important for the PXA clinical management. Despite cellular pleomorphism, mitotic index and the extent of resection are shown to be the main predictors for recurrence-free survival and overall survival rates. The standard therapy management is not yet established. Our patient treatment was associated with a significant ethical dilemma. Respecting patient's wishes to deliver a baby, nor radio or chemo treatments were done. Further studies are necessary to provide factors responsible for malignant transformation of PXA. In addition, in ethically sensitive situation, such as tumor in pregnant patient, good communication, respecting patient's wishes, and a multidisciplinary teamwork is the key for better outcome.

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.

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.

The role of mesencephalic aqueduct obstruction in hydrocephalus development: a case report.

We report on three patients with mesencephalic aqueduct obstruction, which completely blocked the cerebrospinal fluid communication between the third and fourth cerebral ventricle, demonstrated by standard and high-resolution magnetic resonance sequences. Only one patient developed radiological and clinical presentation of hydrocephalus, without radiological signs of increased intraventricular pressure. The remaining two patients did not show clinical signs of hydrocephalus and had a normal radiological presentation of the ventricular system. These findings contradict the classical concept of cerebrospinal fluid physiology. This concept assumes a unidirectional circulation of cerebrospinal fluid through the mesencephalic aqueduct from the secretion site, predominantly in the choroid plexuses, to the resorption site, predominantly in the dural venous sinuses. Therefore, the obstruction of the mesencephalic aqueduct would inevitably lead to triventricular hypertensive hydrocephalus in all patients. The current observations, however, accord with the new concept of cerebrospinal fluid physiology, which postulates that cerebrospinal fluid does not circulate unidirectionally because it is both formed and resorbed along the entire capillary network within the central nervous system.

No Arachnoid Granulations-No Problems: Number, Size, and Distribution of Arachnoid Granulations From Birth to 80 Years of Age.

Introduction: The study aims to quantify changes in the number, size, and distribution of arachnoid granulations during the human lifespan to elucidate their role in cerebrospinal fluid physiology. Material and Methods: 3T magnetic resonance imaging of the brain was performed in 120 subjects of different ages (neonate, 2 years, 10 years, 20 years, 40 years, 60 years, and 80 years) all with the normal findings of the cerebrospinal fluid system (CSF). At each age, 10 male and 10 female subjects were analyzed. Group scanned at neonatal age was re-scanned at the age of two, while all other groups were scanned once. Arachnoid granulations were analyzed on T2 coronal and axial sections. Each arachnoid granulation was described concerning size and position relative to the superior sagittal, transverse, and sigmoid sinuses and surrounding cranial bones. Results: Our study shows that 85% of neonates and 2-year-old children do not have visible arachnoid granulations in the dural sinuses and cranial bones on magnetic resonance imaging. With age, the percentage of patients with arachnoid granulations in the superior sagittal sinus increases significantly, but there is no increase in the sigmoid and transverse sinuses. However, numerous individuals in different age groups do not have arachnoid granulations in dural sinuses. Arachnoid granulations in the cranial bones are found only around the superior sagittal sinus, for the first time at the age of 10, and over time their number increases significantly. From the age of 60 onwards, arachnoid granulations were more numerous in the cranial bones than in the dural sinuses. Conclusion: The results show that the number, size, and distribution of arachnoid granulations in the superior sagittal sinus and surrounding cranial bones change significantly over a lifetime. However, numerous individuals with a completely normal CSF system do not have arachnoid granulations in the dural sinuses, which calls into question their role in CSF physiology. It can be assumed that arachnoid granulations do not play an essential role in CSF absorption as it is generally accepted. Therefore, the lack of arachnoid granulations does not appear to cause problems in intracranial fluid homeostasis.

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.