Delayed Brain Cyst Formation After Gamma Knife Anterior Capsulotomy.

BACKGROUND: Gamma Knife ventral anterior capsulotomy is an effective option to treat refractory obsessive-compulsive disorder. Although well tolerated, complications can develop years after radiosurgery. We describe a case in which abnormal complications induced by very high doses of radiation evolved. CASE DESCRIPTION: A 55-year-old man with refractory obsessive-compulsive disorder was treated with Gamma Knife ventral anterior capsulotomy using a dose of 180 Gy. His obsessive-compulsive symptoms improved, but his condition evolved with a manic episode, cognitive memory changes, visual hallucinations, confabulation, and frontal lobe symptoms. Magnetic resonance imaging showed brain edema in the left hemisphere and a 6-mm brain cyst in the right hemisphere at postoperative month 20. CONCLUSIONS: This case shows the consequences of affecting more fibers related to the anterior frontal region than intended with a radiosurgical procedure and illustrates the importance of careful clinical and imaging follow-up after Gamma Knife ventral anterior capsulotomy.

Review: Post-Intensive Care Syndrome: Unique Challenges in the Neurointensive Care Unit.

Within the last couple of decades, advances in critical care medicine have led to increased survival of critically ill patients, as well as the discovery of notable, long-term health challenges in survivors and their loved ones. The terms post-intensive care syndrome (PICS) and PICS-family (PICS-F) have been used in non-neurocritical care populations to characterize the cognitive, psychiatric, and physical sequelae associated with critical care hospitalization in survivors and their informal caregivers (e.g., family and friends who provide unpaid care). In this review, we first summarize the literature on the cognitive, psychiatric, and physical correlates of PICS and PICS-F in non-neurocritical patient populations and draw attention to their long-term negative health consequences. Next, keeping in mind the distinction between disease-related neurocognitive changes and those that are associated directly with the experience of a critical illness, we review the neuropsychological sequelae among patients with common neurocritical illnesses. We acknowledge the clinical factors contributing to the difficulty in studying PICS in the neurocritical care patient population, provide recommendations for future lines of research, and encourage collaboration among critical care physicians in all specialties to facilitate continuity of care and to help elucidate mechanism(s) of PICS and PICS-F in all critical illness survivors. Finally, we discuss the importance of early detection of PICS and PICS-F as an opportunity for multidisciplinary interventions to prevent and treat new neuropsychological deficits in the neurocritical care population.

Edaravone Reduces Iron-Mediated Hydrocephalus and Behavioral Disorder in Rat by Activating the Nrf2/HO-1 Pathway.

Our previous studies have demonstrated that hemorrhage-derived iron has a key role in causing brain injury after intraventricular hemorrhage (IVH). Based on this finding, we hypothesized that edaravone, a free-radical scavenger, has the potential to alleviate hydrocephalus and neurological deficits post-IVH by suppressing iron-induced oxidative stress. Thus, this study aimed to investigate the efficacy of edaravone for rats with FeCl3 injection, as well as to explore the related molecular mechanism. An experimental model was established in adult male Sprague-Dawley rats via FeCl3 injection into the right lateral ventricle. Edaravone or vehicle was administered immediately, 1 day and 2 days after intraventricular injection. Brain water content, magnetic resonance imaging, neurological score, oxidative stress assays, Western blot analysis, and electron microscopy were employed to evaluate brain injury in these rats. Intraventricular injection of FeCl3 induced brain edema, ventricular dilation, and neurobehavioral disorder in rats. Edaravone treatment significantly attenuated the above symptoms, reduced ependymal cilia and neuron damage, and inhibited oxidative stress (elevated levels of an antioxidant, superoxide dismutase; decreased levels of an oxidant, malondialdehyde). Moreover, edaravone administration effectively activated the Nrf2/HO-1 signaling pathway in rat brain following FeCl3 injection. These results showed that edaravone treatment alleviated brain edema, ventricular expansion, and neurological disorder after FeCl3 injection. The possible mechanism is by protecting ependymal cilia and neurons from oxidative stress injury and activating the Nrf2/HO-1 signaling pathway. These results provide further experimental evidence for edaravone application in the treatment of IVH.

Atorvastatin Pretreatment Attenuates Ischemic Brain Edema by Suppressing Aquaporin 4.

BACKGROUND: Cerebral edema, a serious complication of acute cerebral infarction, has a crucial impact on morbidity and mortality in the early stage of cerebral infarction. And aquaporin 4 (AQP4), a bidirectional water transporting protein, plays a pivotal role in edema formation. At experimental model, it has proven that atorvastatin could exert pleiotropic neuroprotection on acute cerebral infarction independent of its cholesterol-lowering action. It was a common protective manifestation that atorvastatin can reduce the infarct volume and cerebral edema. However, little is known about atorvastatin improving ischemic brain edema by regulating AQP4 expression. This study intended to investigate the neuroprotection effects of atorvastatin pretreatment in rats with cerebral ischemia and further explore the potential relationship between atorvastatin and AQP4 expression. METHODS: Fifty-one adult male Sprague Dawley rats were randomly divided into 3 groups: sham, middle cerebral artery occlusion (MCAO), and atorvastatin pretreatment (Ator) group. For Ator group, 20 mg/kg of atorvastatin injectable suspension was administered once for 7days by gavage before operation, whereas the others were administered the same volume of saline matching. Except for sham group, MCAO and Ator groups were subjected to permanent MCAO by modified intraluminal suture method. Infarct volume, neurological deficit, brain water content (BWC), immunohistochemistry, western blot, and polymerase chain reaction (PCR) were measured at 24 hours after MCAO. RESULTS: Compared with sham group, the mNSS, infarct volume, and BWC of ischemic hemisphere were significantly increased (P < 0.001) in MCAO group. Positive cells and protein levels of p-p38MAPK and AQP4 in peri-infarction were significantly increased (P < 0.01). The mRNA levels of p38MAPK and AQP4 were also prominently upregulated (P < 0.01). Interestingly, preadministration of atorvastatin dramatically decreased infarct volume and the BWC of ischemic hemisphere compared with MCAO group (P < 0.05). The overexpressions of p-p38MAPK and AQP4 in peri-infarction were significantly decreased (P < 0.05) and their mRNA levels were downregulated by atorvastatin pretreatment (P < 0.05). Neurological deficits were also dramatically improved (P < 0.001). CONCLUSION: To the best of our knowledge, this is the first study that demonstrates an effect of atorvastatin on expression of AQP4, and we propose that decreased AQP4 expression through a p38MAPK-suppression pathway may be the mechanism of atorvastatin alleviating ischemic cerebral edema.

17ß-estradiol rescues damages following traumatic brain injury from molecule to behavior in mice.

Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro-Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta-Estradiol (E2) was intraperitoneally administered at 10-80 µg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI-induced brain damages.

Fumarate decreases edema volume and improves functional outcome after experimental stroke.

BACKGROUND: Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl-fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after ischemic stroke in mice. METHODS: Permanent middle cerebral artery occlusion (pMCAO) was performed using adult, male C57BL/6 mice. Thirty minutes after pMCAO, 20mg/kg MMF was administered intravenously. Outcomes were evaluated 6, 24 and 48h after pMCAO. First, we examined whether a bolus of MMF was capable of changing expression of kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor (Nrf)2 in the infarcted brain. Next, we studied the effect of MMF on functional recovery. To explore mechanisms potentially influencing functional changes, we examined infarct volumes, edema formation, the expression of heat shock protein (Hsp)72, hydroxycarboxylic acid receptor 2 (Hcar2), and inducible nitric oxide synthase (iNOS) in the infarcted brain using real-time PCR and Western blotting. Concentrations of a panel of pro- and anti-inflammatory cytokines (IFNγ, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, TNF) were examined in both the infarcted brain tissue and plasma samples 6, 24 and 48h after pMCAO using multiplex electrochemoluminiscence analysis. RESULTS: Administration of MMF increased the protein level of Nrf2 6h after pMCAO, and improved functional outcome at 24 and 48h after pMCAO. MMF treatment did not influence infarct size, however reduced edema volume at both 24 and 48h after pMCAO. MMF treatment resulted in increased Hsp72 expression in the brain 6h after pMCAO. Hcar2 mRNA levels increased significantly 24h after pMCAO, but were not different between saline- and MMF-treated mice. MMF treatment also increased the level of the anti-inflammatory cytokine IL-10 in the brain and plasma 6h after pMCAO, and additionally reduced the level of the pro-inflammatory cytokine IL-12p70 in the brain at 24 and 48h after pMCAO. CONCLUSIONS: A single intravenous bolus of MMF improved sensory-motor function after ischemic stroke, reduced edema formation, and increased the levels of the neuroprotective protein Hsp72 in the brain. The early increase in IL-10 and reduction in IL-12p70 in the brain combined with changes in systemic cytokine levels may also contribute to the functional recovery after pMCAO.

Extensive Microhemorrhages of the Cerebellar Peduncles After High-Altitude Cerebral Edema.

Pichler Hefti, Jacqueline, Philipp Hoigné-Perret, and Raimund Kottke. Extensive microhemorrhages of the cerebellar peduncles after high-altitude cerebral edema. High Alt Med Biol. 18:182-184, 2017.-Neuromagnetic resonance imaging (MRI) of subjects who suffered from high-altitude cerebral edema (HACE) typically shows cerebral microhemorrhages (MH) of the corpus callosum, in particular the splenium, and supratentorial white matter. This is a case report of a 43-year-old male, who suffered from unusually prolonged severe ataxia and amnesia after having been rescued during the ascent to Mount Everest at 6400 m. MRI of the brain 63 days after the incident showed the typical MH in the corpus callosum, but, in addition, extensive MH were found in the middle cerebellar peduncles. These infratentorial MH might reflect the pronounced atactic gait disorder. This case describes the first HACE-associated MH in the cerebellar peduncles in a high-altitude mountaineer indicating a potential vulnerability of infratentorial brain areas to hypobaric hypoxia.

Unfractionated heparin after TBI reduces in vivo cerebrovascular inflammation, brain edema and accelerates cognitive recovery.

BACKGROUND: Severe traumatic brain injury (TBI) may increase the risk of venous thromboembolic complications; however, early prevention with heparinoids is often withheld for its anticoagulant effect. New evidence suggests low molecular weight heparin reduces cerebral edema and improves neurological recovery after stroke and TBI, through blunting of cerebral leukocyte (LEU) recruitment. It remains unknown if unfractionated heparin (UFH) similarly affects brain inflammation and neurological recovery post-TBI. We hypothesized that UFH after TBI reduces cerebral edema by reducing LEU-mediated inflammation and improves neurological recovery. METHODS: CD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. UFH (75 U/kg or 225 U/kg) or vehicle (VEH, 0.9% saline) was administered 2, 11, 20, 27, and 34 hours after TBI. At 48 hours, pial intravital microscopy through a craniotomy was used to visualize live brain LEUs interacting with endothelium and microvascular fluorescein isothiocyanate-albumin leakage. Neurologic function (Garcia Neurological Test, GNT) and body weight loss ratios were evaluated 24 and 48 hours after TBI. Cerebral and lung wet-to-dry ratios were evaluated post mortem. ANOVA with Bonferroni correction was used to determine significance (p < 0.05). RESULTS: Compared to positive controls (CCI), both UFH doses reduced post-TBI in vivo LEU rolling on endothelium, concurrent cerebrovascular albumin leakage, and ipsilateral cerebral water content after TBI. Additionally, only low dose UFH (75 U/kg) improved GNT at both 24 and 48 hours after TBI. High dose UFH (225 U/kg) significantly increased body weight loss above sham at 48 hours. Differences in lung water content and blood pressure between groups were not significant. CONCLUSIONS: UFH after TBI reduces LEU recruitment, microvascular permeability, and brain edema to injured brain. Lower UFH doses concurrently improve neurological recovery whereas higher UFH may worsen functional recovery. Further study is needed to determine if this is caused by increased bleeding from injured brain with higher UFH doses.

Brain edema: a valid endpoint for measuring hepatic encephalopathy?

Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE.

A Novel Brainstem Hemorrhage Model by Autologous Blood Infusion in Rat: White Matter Injury, Magnetic Resonance Imaging, and Neurobehavioral Features.

BACKGROUND: Primary brainstem hemorrhage (BSH) has the highest mortality and morbidity as a subtype of intracerebral hemorrhage. A major limitation of BSH research is the lack of a corresponding animal model. The purpose of this study was to establish a novel rat model of BSH and to characterize the resulting brain injury, especially focusing on white matter injury. METHODS: BSH was produced by stereotactically injecting autologous whole blood into the pons. Time course of hematoma resolution was observed by 7-T magnetic resonance imaging. White matter injury was evaluated in detail by multiple parameters including diffuse tensor imaging (DTI), demyelination, axonal injury, oligodendrocyte degeneration, and oligodendrocyte precursor cell proliferation. Brain water content and neurobehavior were also evaluated. RESULTS: Blood infusion (30 µL) led to a stable, reproducible hematoma in the right basotegmental pons. The hematoma absorption started, became obvious, and was nearly completed at 7, 14, and 30 days, respectively. Hematoma caused obvious brain edema at 3 days. White mater injury was observed pathologically, which was in line with decreased fractional anisotropy (FA) in DTI in the pons. FA reduction was also noticed in the cerebral peduncle and medulla. Behavioral abnormality persisted for at least 14 days and neurofunction was recovered within 1 month. CONCLUSIONS: This novel model can produce a stable hematoma resulting in brain edema, white matter injury, and neurofunctional deficits, which could be useful for future investigation of pathophysiological mechanisms and new treatment evaluation after BSH.

Effects of intracranial meningioma location, size, and surgery on neurocognitive functions: a 3-year prospective study.

OBJECT Current recommendations stress the need for cognitive parameters to be integrated in the evaluation of outcomes for intracranial meningioma surgery. The aim of this prospective study was to examine neurocognitive function in meningioma patients pre- and postoperatively. METHODS Patients with skull base (anterior and middle fossa) and convexity (anterior and posterior) meningiomas (n = 54) underwent neuropsychological examination prior to and 1 year after surgery. A control group (n = 52) of healthy volunteers matched for age, sex, and education underwent the same examination. Assessments included executive, memory, and motor functions with standardized testing. Patients with convexity meningiomas were clinically assessed for parietal association cortex functions. RESULTS All patients performed significantly worse (p < 0.05) in most neurocognitive domains than controls. The skull base group showed more disturbances in memory than the convexity group (p < 0.05). The anterior convexity group showed more deficits in executive function than the posterior convexity group, which presented with parietal association cortex deficits. Verbal deficits were more pronounced in the left hemisphere than in the right hemisphere. Patients with a large tumor (> 4 cm) had more severe neurocognitive deficits than those with a small tumor (< 4 cm). Postoperatively, patients showed no deterioration in neurocognitive function. Instead, significant improvement (p < 0.05) was observed in some executive, motor, and parietal association cortex functions. CONCLUSIONS According to the authors' findings, intracranial meningiomas may cause neurocognitive deficits in patients. Surgery does not cause a deterioration in cognitive function; instead, it may lead to improvements in some functions. Permanent neuropsychological postoperative deficits should be interpreted as tumor-induced rather than due to surgery.

Effects of leonurine on intracerebral haemorrhage by attenuation of perihematomal edema and neuroinflammation via the JNK pathway.

Perihematomal edema plays a critical role in secondary brain injury in intracerebral hemorrhage (ICH), which is associated with inflammation, hematoma toxicity and oxidative stress. In this work, we investigated the protective effects of leonurine, an alkaloid of Herbal Leonuri, and possible mechanisms to provide a basis for a new therapeutic approach for ICH treatment. In in vivo studies, we demonstrated for the first time that leonurine treatment substantially decreased perihematomal edema, ameliorated neurobehavioral function deficits, reduced apoptosis and protected injured cerebral tissue after ICH. These benefits appear to be ascribed to leonurine effectively attenuating bloodbrain barrier (BBB) breakdown in vivo, by inhibiting degradation of hemoglobin and alleviating inflammatory mediator release. In this study, BV-2 cells were exposed in vitro to oxyhemoglobin (OxyHb) at a concentration of 10 µM to mimic neuroinflammation after ICH. Consistent with the results of the in vivo study, leonurine significantly inhibited OxyHbinduced inflammatory proteins expression in BV-2 cells, mainly through inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. This is the first time that leonurine is proved to be capable to protect the injured cerebral tissue after ICH, based on alleviating neuroinflammation and attenuating BBB breakdown to ameliorate perihematomal edema.

Selective astrocytic endothelin-1 overexpression contributes to dementia associated with ischemic stroke by exaggerating astrocyte-derived amyloid secretion.

Endothelin-1 (ET-1) is synthesized by endothelial cells and astrocytes in stroke and in brains of Alzheimer's disease patients. Our transgenic mice with ET-1 overexpression in the endothelial cells (TET-1) showed more severe blood-brain barrier (BBB) breakdown, neuronal apoptosis, and glial reactivity after 2-hour transient middle cerebral artery occlusion (tMCAO) with 22-hour reperfusion and more severe cognitive deficits after 30 minutes tMCAO with 5 months reperfusion. However, the role of astrocytic ET-1 in contributing to poststroke cognitive deficits after tMCAO is largely unknown. Therefore, GET-1 mice were challenged with tMCAO to determine its effect on neurologic and cognitive deficit. The GET-1 mice transiently displayed a sensorimotor deficit after reperfusion that recovered shortly, then more severe deficit in spatial learning and memory was observed at 3 months after ischemia compared with that of the controls. Upregulation of TNF-α, cleaved caspase-3, and Thioflavin-S-positive aggregates was observed in the ipsilateral hemispheres of the GET-1 brains as early as 3 days after ischemia. In an in vitro study, ET-1 overexpressing astrocytic cells showed amyloid secretion after hypoxia/ischemia insult, which activated endothelin A (ETA) and endothelin B (ETB) receptors in a PI3K/AKT-dependent manner, suggesting role of astrocytic ET-1 in dementia associated with stroke by astrocyte-derived amyloid production.

Early brain magnetic resonance imaging can predict short and long-term outcomes after organophosphate poisoning in a rat model.

INTRODUCTION: Magnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. METHODS: Sprague-Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 - no central antidotal treatment (n=10); group 2 - treated with midazolam (MID) at 30 min after poisoning (n=9), group 3 - treated with a combination of MID and scopolamine (SCOP) at 30 min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24 h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel (1)H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. RESULTS: All paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3 h after poisoning. Both MID and MID+SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3h after exposure (1.1 ± 0.07 and 1.42 ± 0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24h after poisoning. MID and MID+SCOP prevented much of the 3h NAA/Cr decrease (1.22 ± 0.05 and 1.32 ± 0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4-0.75 (p<0.05). CONCLUSIONS: MR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties.

Mildly Reduced Brain Swelling and Improved Neurological Outcome in Aquaporin-4 Knockout Mice following Controlled Cortical Impact Brain Injury.

Brain edema following traumatic brain injury (TBI) is associated with considerable morbidity and mortality. Prior indirect evidence has suggested the involvement of astrocyte water channel aquaporin-4 (AQP4) in the pathogenesis of TBI. Here, focal TBI was produced in wild type (AQP4(+/+)) and knockout (AQP4(-/-)) mice by controlled cortical impact injury (CCI) following craniotomy with dura intact (parameters: velocity 4.5 m/sec, depth 1.7 mm, dwell time 150 msec). AQP4-deficient mice showed a small but significant reduction in injury volume in the first week after CCI, with a small improvement in neurological outcome. Mechanistic studies showed reduced intracranial pressure at 6 h after CCI in AQP4(-/-) mice, compared with AQP4(+/+) control mice (11 vs. 19 mm Hg), with reduced local brain water accumulation as assessed gravimetrically. Transmission electron microscopy showed reduced astrocyte foot-process area in AQP4(-/-) mice at 24 h after CCI, with greater capillary lumen area. Blood-brain barrier disruption assessed by Evans blue dye extravasation was similar in AQP4(+/+) and AQP4(-/-) mice. We conclude that the mildly improved outcome in AQP4(-/-) mice following CCI results from reduced cytotoxic brain water accumulation, though concurrent cytotoxic and vasogenic mechanisms in TBI make the differences small compared to those seen in disorders where cytotoxic edema predominates.

Prognostic implication of preoperative behavior changes in patients with primary high-grade meningiomas.

High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (P = 0.066) and patients older than 55 years (P = 0.018). They correlated with frontal location (P = 0.013), tumor size (P = 0.023), microscopic brain invasion (P = 0.015), and brain edema (P = 0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas.