Matrix Metalloproteinases in Cardioembolic Stroke: From Background to Complications.

Matrix metalloproteinases (MMPs) are endopeptidases participating in physiological processes of the brain, maintaining the blood-brain barrier integrity and playing a critical role in cerebral ischemia. In the acute phase of stroke activity, the expression of MMPs increase and is associated with adverse effects, but in the post-stroke phase, MMPs contribute to the process of healing by remodeling tissue lesions. The imbalance between MMPs and their inhibitors results in excessive fibrosis associated with the enhanced risk of atrial fibrillation (AF), which is the main cause of cardioembolic strokes. MMPs activity disturbances were observed in the development of hypertension, diabetes, heart failure and vascular disease enclosed in CHA2DS2VASc score, the scale commonly used to evaluate the risk of thromboembolic complications risk in AF patients. MMPs involved in hemorrhagic complications of stroke and activated by reperfusion therapy may also worsen the stroke outcome. In the present review, we briefly summarize the role of MMPs in the ischemic stroke with particular consideration of the cardioembolic stroke and its complications. Moreover, we discuss the genetic background, regulation pathways, clinical risk factors and impact of MMPs on the clinical outcome.

Comparison of QEEG Findings before and after Onset of Post-COVID-19 Brain Fog Symptoms.

Previous research and clinical reports have shown that some individuals after COVID-19 infection may demonstrate symptoms of so-called brain fog, manifested by cognitive impairment and disorganization in behavior. Meanwhile, in several other conditions, related to intellectual function, a specific pattern of changes in electric brain activity, as recorded by quantitative electroencephalography (QEEG) has been documented. We hypothesized, that in post-COVID brain fog, the subjective complaints may be accompanied by objective changes in the QEEG profile. In order to test this hypothesis, we have performed an exploratory study on the academic staff of our University with previous records of QEEG originating in the pre-COVID-19 era. Among them, 20 subjects who revealed neurological problems in the cognitive sphere (confirmed as covid fog/brain fog by a clinical specialist) after COVID-19 infection were identified. In those individuals, QEEG was performed. We observed, that opposite to baseline QEEG records, increased Theta and Alpha activity, as well as more intensive sensimotor rhythm (SMR) in C4 (right hemisphere) in relation to C3 (left hemisphere). Moreover, a visible increase in Beta 2 in relation to SMR in both hemispheres could be documented. Summarizing, we could demonstrate a clear change in QEEG activity patterns in individuals previously not affected by COVID-19 and now suffering from post-COVID-19 brain fog. These preliminary results warrant further interest in delineating their background. Here, both neuroinflammation and psychological stress, related to Sars-CoV2-infection may be considered. Based on our observation, the relevance of QEEG examination as a supportive tool for post-COVID clinical workup and for monitoring the treatment effects is also to be explored.

Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research.

The appearance of the SARS-CoV-2 virus initiated many studies on the effects of the virus on the human body. So far, its negative influence on the functioning of many morphological and physiological units, including the nervous system, has been demonstrated. Consequently, research has been conducted on the changes that SARS-CoV-2 may cause in the cholinergic system. The aim of this study is to review the latest research from the years 2020/2021 regarding disorders in the cholinergic system caused by the SARS-CoV-2 virus. As a result of the research, it was found that the presence of the COVID-19 virus disrupts the activity of the cholinergic system, for example, causing the development of myasthenia gravis or a change in acetylcholine activity. The SARS-CoV-2 spike protein has a sequence similar to neurotoxins, capable of binding nicotinic acetylcholine receptors (nAChR). This may be proof that SARS-CoV-2 can bind nAChR. Nicotine and caffeine have similar structures to antiviral drugs, capable of binding angiotensin-converting enzyme 2 (ACE 2) epitopes that are recognized by SARS-CoV-2, with the potential to inhibit the formation of the ACE 2/SARS-CoV-2 complex. The blocking is enhanced when nicotine and caffeine are used together with antiviral drugs. This is proof that nAChR agonists can be used along with antiviral drugs in COVID-19 therapy. As a result, it is possible to develop COVID-19 therapies that use these compounds to reduce cytokine production. Another promising therapy is non-invasive stimulation of the vagus nerve, which soothes the body's cytokine storm. Research on the influence of COVID-19 on the cholinergic system is an area that should continue to be developed as there is a need for further research. It can be firmly stated that COVID-19 causes a dysregulation of the cholinergic system, which leads to a need for further research, because there are many promising therapies that will prevent the SARS-CoV-2 virus from binding to the nicotinic receptor. There is a need for further research, both in vitro and in vivo. It should be noted that in the functioning of the cholinergic system and its connection with the activity of the COVID-19 virus, there might be many promising dependencies and solutions.

Reply to Cafiero et al. Comment on "Kopanska et al. Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672".

We have carefully read the Letter to the Editor by Concetta Cafiero, Alessandra Micera, Agnese Re, Beniamino Schiavone, Giulio Benincasa, and Raffaele Palmirotta related to our paper entitled "Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research" [...].

Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.

AIM OF THE STUDY: To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. CLINICAL RATIONALE FOR THE STUDY: G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. MATERIAL AND METHODS: A controlled traumatic right sciatic nerve lesion was set using a waterjet device. Three treatment groups were created. In the first group, G-CSF was administered after sciatic nerve injury. The second group received G-CSF before and after trauma, while the third group was treated with glucose 5%-solution. Sciatic nerve function was assessed clinically and electrophysiologically at day 1, and after weeks 1, 2, 4 and 6. Additionally, α-motoneurons of the spinal cord and sciatic nerve fibres were counted at week 6. RESULTS: Clinically, rats in both G-CSF groups improved faster compared to the control group. Additionally, animals treated with G-CSF had a significantly better improvement of motor potential amplitude and motor nerve conduction velocity at week 6 (p < 0.05). Histologically, G-CSF treatment resulted in a significantly higher number of α-motoneurons and small myelinated nerve fibres compared to placebo treatment (p < 0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: Under G-CSF treatment, the recovery of motor nerve conduction velocity and amplitude was enhanced. Further, signs of nerve regeneration and preservation of α-motoneurons were observed. These results indicate that G-CSF might accelerate and intensify the recovery of injured nerves. Thus, treatment with G-CSF may be beneficial for patients with peripheral nerve damage, and should be explored in further clinical studies.

The Use of Quantitative Electroencephalography (QEEG) to Assess Post-COVID-19 Concentration Disorders in Professional Pilots: An Initial Concept.

Announced by WHO in 2020, the global COVID-19 pandemic caused by SARS-CoV-2 has affected many people, leading to serious health consequences. These consequences are observed in the daily lives of infected patients as various dysfunctions and limitations. More and more people are suffering post-COVID-19 complications that interfere with or completely prevent them from working or even functioning independently on a daily basis. The aim of our study was to demonstrate that innovative quantitative electroencephalography (QEEG) can be used to assess cognitive function disorders reported after the COVID-19 pandemic. It is worth noting that no similar study has been conducted to date in a group of pilots. The QEEG method we used is currently one of the basic neurological examinations, enabling easy observation of post-COVID-19 changes in the nervous system. With the innovativeness of this technique, our study shows that the use of quantitative electroencephalography can be a precursor in identifying complications associated with cognitive function disorders after COVID-19. Our study was conducted on twelve 26-year-old pilots. All participants had attended the same flight academy and had contracted SARS-CoV-2 infection. The pilots began to suspect COVID-19 infection when they developed typical symptoms such as loss of smell and taste, respiratory problems, and rapid fatigue. Quantitative electroencephalography (QEEG), which is one of the most innovative forms of diagnostics, was used to diagnose the patients. Comparison of the results between the study and control groups showed significantly higher values of all measurements of alpha, theta, and beta2 waves in the study group. In the case of the sensorimotor rhythm (SMR), the measurement results were significantly higher in the control group compared to the study group. Our study, conducted on pilots who had recovered from COVID-19, showed changes in the amplitudes of brain waves associated with relaxation and concentration. The results confirmed the issues reported by pilots as evidenced by the increased amplitudes of alfa, theta, and beta2 waves. It should be emphasized that the modern diagnostic method (QEEG) presented here has significant importance in the medical diagnosis of various symptoms and observation of treatment effects in individuals who have contracted the SARS-CoV-2 virus. The present study demonstrated an innovative approach to the diagnosis of neurological complications after COVID-19.

Prolonged course of brain edema and neurological recovery in a translational model of decompressive craniectomy after closed head injury in mice.

Background: The use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments. Objective: The goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model. Methods: Male mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed. Results: Animals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma. Conclusion: In prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.

MiniQEEG and Neurofeedback in Diagnosis and Treatment of COVID-19-Related Panic Attacks: A Case Report.

BACKGROUND: Both the global COVID-19 pandemic situation, as well as the current political situation in Eastern Europe may exacerbate anxiety and contribute to stress-related disorders such as panic disorder. Electroencephalography (EEG)-based neurofeedback provides both assessment of the subject's brainwave activity as well as the possibility of its therapeutic correction. It is possible that it can be implemented as an auxiliary treatment in panic disorders of different origin. The aim of this feasibility study was to demonstrate (both short- and long-term) effectiveness of neurofeedback therapy in a patient with previously diagnosed panic attacks, related to fear of COVID-19 infection. METHODS: We report the case study of a 47-year-old man affected by panic attacks, related to his profound, constant fear of COVID-19 infection and its sequelae. For the initial diagnostic workup, several clinical and research tools were used: 1. Baseline psychological exam; 2. Anxiety-targeted interview performed by miniQEEG therapist; 3. Analysis of previous clinical test results (EEG record/lab blood test); and 4. The miniQEEG exam (central strip recording Cz-C3-C4), The patient was subjected to regular EEG Neurofeedback sessions for two consecutive months. After completing the treatment, follow-up tests, as listed above were repeated immediately after completing the whole treatment program, as well as 1 and 2 years later. MiniQEEG results were compared with healthy control (age-matched male subject not affected with panic attacks) and evaluated over the time that the subject was involved in the study. RESULTS: Initially, the patient was suffering from severe panic attacks accompanied by vegetative symptoms and from destructive and negative thoughts. After 8 consecutive weeks of treatment encompassing sixteen QEEG neurofeedback training sessions (each lasting 30 min), a subjective improvement of his complaints was reported. More importantly, QEEG records of the patient also improved, approximating the pattern of QEEG recorded in the healthy control. CONCLUSION: In this single case-based feasibility analysis, we demonstrate that systematic application of QEEG-Neurofeedback may result in manifest and durable therapeutic effect. Of note, use of this treatment may be a valuable option for patients with panic attack/panic disorder, especially if related to the psychological burden of the COVID-19/war era. Future studies on a larger patient population, especially with a longitudinal/prospective design, are warranted.

Characterisation of Selected Materials in Medical Applications.

Tissue engineering is an interdisciplinary field of science that has developed very intensively in recent years. The first part of this review describes materials with medical and dental applications from the following groups: metals, polymers, ceramics, and composites. Both positive and negative sides of their application are presented from the point of view of medical application and mechanical properties. A variety of techniques for the manufacture of biomedical components are presented in this review. The main focus of this work is on additive manufacturing and 3D printing, as these modern techniques have been evaluated to be the best methods for the manufacture of medical and dental devices. The second part presents devices for skull bone reconstruction. The materials from which they are made and the possibilities offered by 3D printing in this field are also described. The last part concerns dental transitional implants (scaffolds) for guided bone regeneration, focusing on polylactide-hydroxyapatite nanocomposite due to its unique properties. This section summarises the current knowledge of scaffolds, focusing on the material, mechanical and biological requirements, the effects of these devices on the human body, and their great potential for applications.

Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis.

In the past, water homeostasis of the brain was understood as a certain quantitative equilibrium of water content between intravascular, interstitial, and intracellular spaces governed mostly by hydrostatic effects i.e., strictly by physical laws. The recent achievements in molecular bioscience have led to substantial changes in this regard. Some new concepts elaborate the idea that all compartments involved in cerebral fluid homeostasis create a functional continuum with an active and precise regulation of fluid exchange between them rather than only serving as separate fluid receptacles with mere passive diffusion mechanisms, based on hydrostatic pressure. According to these concepts, aquaporin-4 (AQP4) plays the central role in cerebral fluid homeostasis, acting as a water channel protein. The AQP4 not only enables water permeability through the blood-brain barrier but also regulates water exchange between perivascular spaces and the rest of the glymphatic system, described as pan-cerebral fluid pathway interlacing macroscopic cerebrospinal fluid (CSF) spaces with the interstitial fluid of brain tissue. With regards to this, AQP4 makes water shift strongly dependent on active processes including changes in cerebral microcirculation and autoregulation of brain vessels capacity. In this paper, the role of the AQP4 as the gatekeeper, regulating the water exchange between intracellular space, glymphatic system (including the so-called neurovascular units), and intravascular compartment is reviewed. In addition, the new concepts of brain edema as a misbalance in water homeostasis are critically appraised based on the newly described role of AQP4 for fluid permeation. Finally, the relevance of these hypotheses for clinical conditions (including brain trauma and stroke) and for both new and old therapy concepts are analyzed.

Changes in EEG Recordings in COVID-19 Patients as a Basis for More Accurate QEEG Diagnostics and EEG Neurofeedback Therapy: A Systematic Review.

INTRODUCTION AND PURPOSE: The SARS-CoV-2 virus is able to cause abnormalities in the functioning of the nervous system and induce neurological symptoms with the features of encephalopathy, disturbances of consciousness and concentration and a reduced ability to sense taste and smell as well as headaches. One of the methods of detecting these types of changes in COVID-19 patients is an electroencephalogram (EEG) test, which allows information to be obtained about the functioning of the brain as well as diagnosing diseases and predicting their consequences. The aim of the study was to review the latest research on changes in EEG in patients with COVID-19 as a basis for further quantitative electroencephalogram (QEEG) diagnostics and EEG neurofeedback training. Description of the state of knowledge: Based on the available scientific literature using the PubMed database from 2020 and early 2021 regarding changes in the EEG records in patients with COVID-19, 17 publications were included in the analysis. In patients who underwent an EEG test, changes in the frontal area were observed. A few patients were not found to be responsive to external stimuli. Additionally, a previously non-emerging, uncommon pattern in the form of continuous, slightly asymmetric, monomorphic, biphasic and slow delta waves occurred. CONCLUSION: The results of this analysis clearly indicate that the SARS-CoV-2 virus causes changes in the nervous system that can be manifested and detected in the EEG record. The small number of available articles, the small number of research groups and the lack of control groups suggest the need for further research regarding the short and long term neurological effects of the SARS-CoV-2 virus and the need for unquestionable confirmation that observed changes were caused by the virus per se and did not occur before. The presented studies described non-specific patterns appearing in encephalograms in patients with COVID-19. These observations are the basis for more accurate QEEG diagnostics and EEG neurofeedback training.

Head Injury without Head Blow? A Rare Case of Subdural Hematoma Associated with Minute Arachnoid Cyst in a Teenage Skater.

BACKGROUND: Skateboarding has been reported to cause diverse kinds of injuries, including head trauma. However, the risk of brain injury without direct blow to the head seems to be underestimated. In particular, the impact of the inertial forces related to the vigorous character of skateboarding tricks is not sufficiently recognized. CASE DESCRIPTION: In our report, we demonstrate a case of chronic subdural hematoma developing without previous blow to the head in a 17-year-old skater bearing small frontal convexity arachnoid cyst. CONCLUSION: Based on the described case, the possibility of acceleration and angular forces related to skate park leisure activities resulting in subdural hematoma needs to be discussed. This risk should be critically appraised in patients carrying arachnoid cyst as a malformation predisposing to develop subdural bleeding.

The effects of selective brain hypothermia and decompressive craniectomy on brain edema after closed head injury in mice.

Intractable brain edema remains one of the main causes of death after traumatic brain injury (TBI). Brain hypothermia and decompressive craniectomy have been considered as potential therapies. The goal of our experimental study was to determine if selective hypothermia in combination with craniectomy could modify the development of posttraumatic brain edema. Male CD-1 mice were anesthetized with halothane and randomly assigned into the following groups: sham-operated (n = 5), closed head injury (CHI) alone (n = 5), CHI followed by craniectomy at 1 h post-TBI (n = 5) and CHI + craniectomy and selective hypothermia (focal brain cooling using cryosurgery device) maintained for 5 h (n = 5). Animals were sacrificed at 7 h posttrauma and brains were removed, sagittally dissected and dried. The brain water content of separate hemispheres was calculated from the weight difference before and after drying. In the CHI alone group there was no significant increase in brain water content in both the ipsi- and contralateral hemispheres (80.59 +/- 1% and 78.74 +/- 0.9% in the CHI group vs. 79.31 +/- 0.7% and 79.01 +/- 0.3% in the sham group, respectively). Brain edema was significantly increased ipsilaterally in the trauma + craniectomy group (82.11 +/- 0.6%, p < 0.05), but not in the trauma + craniectomy + hypothermia group (81.52 +/- 1.1%, p > 0.05) as compared to the sham group (79.31 +/- 0.7%). These data suggest that decompressive craniectomy leads to an increase in brain water content after CHI. Additional focal hypothermia may be an effective approach in the treatment of posttraumatic brain edema.

Brain Edema Formation and Functional Outcome After Surgical Decompression in Murine Closed Head Injury Are Modulated by Acetazolamide Administration.

Acetazolamide (ACZ), carbonic anhydrase inhibitor, has been successfully applied in several neurosurgical conditions for diagnostic or therapeutic purposes. Furthermore, neuroprotective and anti-edematous properties of ACZ have been postulated. However, its use in traumatic brain injury (TBI) is limited, since ACZ-caused vasodilatation according to the Monro-Kellie doctrine may lead to increased intracranial blood volume / raise of intracranial pressure. We hypothesized that these negative effects of ACZ will be reduced or prevented, if the drug is administered after already performed decompression. To test this hypothesis, we used a mouse model of closed head injury (CHI) and decompressive craniectomy (DC). Mice were assigned into following experimental groups: sham, DC, CHI, CHI+ACZ, CHI+DC, and CHI+DC+ACZ (n = 8 each group). 1d and 3d post injury, the neurological function was assessed according to Neurological Severity Score (NSS) and Beam Balance Score (BBS). At the same time points, brain edema was quantified by MRI investigations. Functional impairment and edema volume were compared between groups and over time. Among the animals without skull decompression, the group additionally treated with acetazolamide demonstrated the most severe functional impairment. This pattern was reversed among the mice with decompressive craniectomy: CHI+DC treated but not CHI+DC+ACZ treated animals showed a significant neurological deficit. Accordingly, radiological assessment revealed most severe edema formation in the CHI+DC group while in CHI+DC+ACZ animals, volume of brain edema did not differ from DC-only animals. In our CHI model, the response to acetazolamide treatment varies between animals with decompressive craniectomy and those without surgical treatment. Opening the cranial vault potentially creates an opportunity for acetazolamide to exert its beneficial effects while vasodilatation-related risks are attenuated. Therefore, we recommend further exploration of this potentially beneficial drug in translational research projects.

Changes in Posttraumatic Brain Edema in Craniectomy-Selective Brain Hypothermia Model Are Associated With Modulation of Aquaporin-4 Level.

Both hypothermia and decompressive craniectomy have been considered as a treatment for traumatic brain injury. In previous experiments we established a murine model of decompressive craniectomy and we presented attenuated edema formation due to focal brain cooling. Since edema development is regulated via function of water channel proteins, our hypothesis was that the effects of decompressive craniectomy and of hypothermia are associated with a change in aquaporin-4 (AQP4) concentration. Male CD-1 mice were assigned into following groups (n = 5): sham, decompressive craniectomy, trauma, trauma followed by decompressive craniectomy and trauma + decompressive craniectomy followed by focal hypothermia. After 24 h, magnetic resonance imaging with volumetric evaluation of edema and contusion were performed, followed by ELISA analysis of AQP4 concentration in brain homogenates. Additional histopathological analysis of AQP4 immunoreactivity has been performed at more remote time point of 28d. Correlation analysis revealed a relationship between AQP4 level and both volume of edema (r 2 = 0.45, p < 0.01, **) and contusion (r 2 = 0.41, p < 0.01, **) 24 h after injury. Aggregated analysis of AQP4 level (mean ± SEM) presented increased AQP4 concentration in animals subjected to trauma and decompressive craniectomy (52.1 ± 5.2 pg/mL, p = 0.01; *), but not to trauma, decompressive craniectomy and hypothermia (45.3 ± 3.6 pg/mL, p > 0.05; ns) as compared with animals subjected to decompressive craniectomy only (32.8 ± 2.4 pg/mL). However, semiquantitative histopathological analysis at remote time point revealed no significant difference in AQP4 immunoreactivity across the experimental groups. This suggests that AQP4 is involved in early stages of brain edema formation after surgical decompression. The protective effect of selective brain cooling may be related to change in AQP4 response after decompressive craniectomy. The therapeutic potential of this interaction should be further explored.

Confocal Laser Endomicroscopy in Neurosurgery-An Alternative to Instantaneous Sections?

OBJECTIVE: Intraoperative distinction of brain tumor from surrounding brain is a crucial challenge in neuro-oncologic surgery. We directly compared confocal laser endomicroscopy (CLE) findings with intraoperative instantaneous sections by the neuropathologist in a blinded fashion. METHODS: The imaging device comprises a rigid endoscope with Hopkins rod lenses and a red wave length laser with a scanning depth of 80 µm. Brain tumor samples of 100 patients were investigated. Tissue samples were simultaneously investigated by the neuropathologist and with CLE. The tissue was not prepared or stained before CLE analysis. RESULTS: CLE could be performed in all cases. Sensitivity for detection of a correct final diagnosis by CLE on site was 82%-90% for high-grade gliomas (26/32), low-grade gliomas (9/10), schwannomas (7/8), and meningiomas (28/34). Sensitivity of only 37% (6/16) was achieved for metastasis (6/16). CONCLUSIONS: With intraoperative CLE, it is possible to obtain an on-site histologic diagnosis with a high sensitivity in many tumors. Although definitive histologic classification requires further neuropathologic investigation, these results show that CLE could fill the gap between tissue resection and microscopic analysis. This could ultimately help neurosurgeons to scan brain tissue for tumor remnants on a microscopic scale without having to resect it first. Further development of the device and further investigations are needed before this technique can become part of the neurosurgical routine in specific cases.

Selective Brain Hypothermia Mitigates Brain Damage and Improves Neurological Outcome after Post-Traumatic Decompressive Craniectomy in Mice.

Hypothermia and decompressive craniectomy (DC) have been considered as treatment for traumatic brain injury. The present study investigates whether selective brain hypothermia added to craniectomy could improve neurological outcome after brain trauma. Male CD-1 mice were assigned into the following groups: sham; DC; closed head injury (CHI); CHI followed by craniectomy (CHI+DC); and CHI+DC followed by focal hypothermia (CHI+DC+H). At 24 h post-trauma, animals were subjected to Neurological Severity Score (NSS) test and Beam Balance Score test. At the same time point, magnetic resonance imaging using a 9.4 Tesla scanner and subsequent volumetric evaluation of edema and contusion were performed. Thereafter, the animals were sacrificed and subjected to histopathological analysis. According to NSS, there was a significant impairment among all the groups subjected to trauma. Animals with both trauma and craniectomy performed significantly worse than animals with craniectomy alone. This deleterious effect disappeared when additional hypothermia was applied. BBS was significantly worse in the CHI and CHI+DC groups, but not in the CHI+DC+H group, compared to the sham animals. Edema and contusion volumes were significantly increased in CHI+DC animals, but not in the CHI+DC+H group, compared to the DC group. Histopathological analysis showed that neuronal loss and contusional blossoming could be attenuated by application of selective brain hypothermia. Selective brain cooling applied post-trauma and craniectomy improved neurological function and reduced structural damage and may be therefore an alternative to complication-burdened systemic hypothermia. Clinical studies are recommended in order to explore the potential of this treatment.

Factors Affecting Outcome in Treatment of Chronic Subdural Hematoma in ICU Patients: Impact of Anticoagulation.

BACKGROUND: The use of anticoagulants and older age are the main risk factors for chronic subdural hematoma (CSDH). Because the age of the population and use of anticoagulants are increasing, a growing number of CSDH cases is expected. To address this issue, we analyzed the impact of anticoagulants on postsurgical outcome in patients in the intensive care unit (ICU). METHODS: Demographic data, coagulation parameters, surgical details, radiologic appearance of hematoma, Glasgow Coma Scale (GCS) score on admission, and Glasgow Outcome Scale (GOS) score on discharge were retrieved and retrospectively analyzed in 98 patients with CSDH treated in the neurosurgical ICU using correlation coefficient tests and multivariate analysis test. RESULTS: Overall outcome was good (GOS score 4 and 5) in 55.1% of patients. Overall mortality was 9.1%. There was a correlation between GCS score on admission and GOS score. There was no correlation between hematoma thickness/radiologic appearance and impaired coagulation. Disturbance in thrombocyte function (usually resulting from aspirin intake) correlated with improved outcome, whereas warfarin-related coagulopathy correlated with poor recovery. Nevertheless, patients with thrombocytopathy presented with better initial GCS scores. Neither hematoma size nor recurrence rate affected the outcome. CONCLUSIONS: The size of CSDH was not associated with poor outcome and is not necessarily determined by the use of anticoagulants. Coagulopathy does not rule out a good outcome, but the impact of anticoagulation on treatment results in CSDH varies between the main groups of drugs (warfarin vs. antiplatelet drugs). Patients in good neurologic condition on ICU admission have better chances of recovery.