MMP-9, TIMP-1 and S100B protein as markers of ischemic stroke in patients after carotid artery endarterectomy.

Ischemic stroke is the main cause of permanent disability in adult patients. No commonly accepted method were discovered to predict stroke before the first symptoms. Activation of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMP) and S100B protein may be observe in patients with symptomatic carotid artery stenosis. Hemorrhagic transformation of ischemic stroke may be associated with changes in MMP, TIMP and S100B. AIM: The aim of this study was to determine if MMP-9, TIMP-1 and S-100B protein may markers of forthcoming ischemic stroke in patients undergoing carotid endarterectomy. MATERIALS AND METHODS: Blood samples were taken and an analysis of circulating proteins (MMP-9, TIMP-1, S100B) 73 subsequent patients with carotid artery stenosis ≥70% (33 asymptomatic and 40 symptomatic), who were referred for potential revascularization. RESULTS: A statistically significant difference was found between MMP- 9 levels in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy. Also, average TIMP-1 levels in patients with ischemic stroke and stenosis ≥70% were statistically significantly higher than the average levels in patients after endarterectomy. In terms of S-100B, a higher mean value was observed in patients with stroke than in endarterectomy group. No statistical differences were found in the levels of that proteins in the hemorrhagic transformation of ischemic stroke. CONCLUSIONS: Increased levels of MMP-9, TIMP-1 and S-100B in patients with ischemic stroke compared to patients with asymptomatic carotid stenosis after endarterectomy showed that abovementioned proteins may be a good predictive factor of ischemic stroke in patients undergoing carotid endarterectomy.

Clinical features of neurological patients with coronavirus 2019: an observational study of one centre.

BACKGROUND: Since the emergence of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) in Wuhan, China, it has been extensively studied by many scientists. Susceptibility to SARS-CoV-2 infection is shown by people of all ages, especially those with different comorbidities. Our goal was to describe the clinical characteristics, treatment, course, and outcome of COVID-19 in patients with pre-existing neurological disorders. METHOD: We retrospectively studied 70 patients with COVID-19 and previous neurological diseases who were treated in the Central Clinical Hospital of the Ministry of the Interior and Administration from 16 March to 15 June 2020. Demographic data, symptoms, image data, laboratory results, treatment methods and results, clinical signs and symptoms of patients hospitalised due to CNS diseases with COVID-19 were collected. RESULTS: The average age of hospitalised patients was 72, and the majority (63%) were women (44/70). The most common neurological disease was dementia, which was present in almost a third of patients (30.76%), followed by ischaemic stroke (24.61%). Chest imaging showed the presence of interstitial changes in 47% (33) of patients. Laboratory tests revealed increased total blood cells, increased levels of C-reactive protein, procalcitonin, D-dimers, liver indicator markers and IL-6 in the most severely affected patients. The treatment of patients was focused on monitoring their clinical condition, and supporting respiratory inefficiency with passive oxygen therapy and mechanical ventilation. According to the guidelines of the Hospital Therapeutic Committee, pharmacological treatment (Arechin®, Kaletra®) was introduced in cases without contraindications. In patients with moderate COVID-19, antimalarial or antiviral agents were applied (78%). 30% of our observed patients died during the hospitalisation. CONCLUSIONS: We studied a select group of patients (elderly, with comorbidities, and moderate or severe COVID-19 course). Pre-existing neurological disorders were additionally associated with a poorer prognosis and a high fatality rate (30%). Dementia and CNS vascular disorder were the most frequent pre-existing neurological conditions. The neurological symptoms of COVID-19 were various. We observed impaired consciousness, dizziness, headache, nausea, myalgia, psychomotor agitation and slowness, delirium, and psychoses. Further analysis is needed to elucidate the incidence of COVID-19 neurological complications.

Brain Functional Reserve in the Context of Neuroplasticity after Stroke.

Stroke is the second cause of death and more importantly first cause of disability in people over 40 years of age. Current therapeutic management of ischemic stroke does not provide fully satisfactory outcomes. Stroke management has significantly changed since the time when there were opened modern stroke units with early motor and speech rehabilitation in hospitals. In recent decades, researchers searched for biomarkers of ischemic stroke and neuroplasticity in order to determine effective diagnostics, prognostic assessment, and therapy. Complex background of events following ischemic episode hinders successful design of effective therapeutic strategies. So far, studies have proven that regeneration after stroke and recovery of lost functions may be assigned to neuronal plasticity understood as ability of brain to reorganize and rebuild as an effect of changed environmental conditions. As many neuronal processes influencing neuroplasticity depend on expression of particular genes and genetic diversity possibly influencing its effectiveness, knowledge on their mechanisms is necessary to understand this process. Epigenetic mechanisms occurring after stroke was briefly discussed in this paper including several mechanisms such as synaptic plasticity; neuro-, glio-, and angiogenesis processes; and growth of axon.

MMP-9 and/or TIMP as predictors of ischaemic stroke in patients with symptomatic and asymptomatic atherosclerotic stenosis of carotid artery treated by stenting or endarterectomy - A review.

We still lack an optimal tool to predict ischaemic stroke in patients with symptomatic and asymptomatic carotid stenosis (CS). It has already been shown that patients at increased risk of ischaemic stroke can be identified based on the elevated plasma levels of metalloproteinases (MMPs) and reduced activity tissue inhibitor of metalloproteinase (TIMP). There are few studies presenting the role of MMP-9 and TIMP in ischaemic stroke both in patients with symptomatic and asymptomatic CS treated with stenting or endarterectomy, however we have not found any published review summarizing the role of abovementioned markers. MEDLINE was accessed via Pub Med, and searched for published studies that analyzed MMP-9 and TIMP levels in patients with asymptomatic and symptomatic internal carotid stenosis and/or examined these parameters as potential risk markers for ischaemic stroke. A total of 13 articles documenting the outcomes of patients with symptomatic or asymptomatic carotid stenosis treated by carotid stenting or endarterectomy, were analyzed. Statistically significant differences in the levels of MMP-9 and/or TIMP in patients with symptomatic and asymptomatic CS have been reported. Also the concentrations of MMP-9 and TIMP in CS patients subjected to stenting or endarterectomy were higher than in baseline group. Moreover higher levels of MMP-9 and decreased TIMP was reported to be associated with the risk of restenosis. This systematic review shows that available evidence regarding the dynamics of MMP-9 and TIMP levels may be a predictor of cerebrovascular events in both symptomatic and asymptomatic carotid stenosis in patients treated with stenting or endarterectomy.

[Evaluation of the effectiveness of endovascular embolization for the treatment of ruptured cerebral aneurysms]. / Ocena skutecznosci embolizacji wewnatrznaczyniowej w leczeniu peknietych tetniaków mózgu.

Endovascular embolization of ruptured intracranial aneurysms is a relatively new and still developing technique, therefore its efficiency and risks should be assessed recurrently, including also results obtained in national centers. AIM: The aim of the study was to present a synthetic review of the literature, which, including the data published by the Polish centers, typify the global assessment of the effectiveness and early complication of endovascular embolization in patients with ruptured brain aneurysms. MATERIALS AND METHODS: Our review of the literature includes 24 papers listed in PubMed and Medline, including also two Polish case series. The following data were extracted from the publications and compiled into global characteristics of a case series: basic characteristic of the study group, neurological status on admission, feasibility of procedure, incidence of complications and their type, outcome at discharge and intraoperative morbidity and mortality. RESULTS: Effective embolization was feasible in 94.4% of patients. Total occlusion of the cerebral aneurysm (99-100%) during initial procedure was achieved in 60.7% of patients. Intraoperative complications occurred in 12.6% of individuals. The most frequent type of intraoperative complication was thromboembolism, which occurred in 6%. As much as 65.2% of patients scored 4 or 5 in GOS on discharge. CONCLUSIONS: Endovascular embolization is highly effective in the treatment of ruptured cerebral aneurysms, featured also by a low rate of intra-procedural complications. The majority of patients are discharged in good shape and neurological status, scoring 4-5 in GOS.

Early outcomes and perioperative complications of endovascular embolization in patients with aneurysmal SAH.

BACKGROUND: We still lack reliable data on the outcomes of endovascular coiling for ruptured cerebral aneurysms. As this is still an evolving technique, the outcomes of the procedures performed in the past and more recently cannot be directly compared. We present the early outcomes of endovascular coiling in a relatively large group of patients with ruptured intracranial aneurysms. METHOD: The study included 190 consecutive patients (a total of 216 aneurysms) subjected to endovascular coiling in 2006-2013 (127 women aged 56±13 years and 63 men aged 50± 15 years). Up to 87.5% of the aneurysms were located within anterior circulation. Most patients presented with "mild to moderate" subarachnoid hemorrhages (85% of Hunt &Hess scores 1-3, and 72% of Fisher scores 1-3). RESULTS: Embolization was feasible in 176 (92.6%) patients. In 14 cases, the embolization was not attainable due to unfavorable anatomy of the aneurysm, intraoperative vasospasm and/or aneurysm rupture, or prolapse of a coil. Early complications related to the procedure were recorded in 23 (13.1%) patients. The most common perioperative complication was aneurysm rupture. All fatal complications occurred in patients with aneurysms located at the anterior circle of Willis. At the time of discharge, 126 patients scored 4 or 5 on the Glasgow Outcome Scale. CONCLUSIONS: Endovascular embolization is an effective and relatively safe method for treatment of ruptured cerebral aneurysms. Complications related to the procedure are significantly less frequent in the case of vertebral-basilar complex aneurysms.

Subtotal resection of vestibular schwannoma with subsequent Gamma Knife irradiation - tumor growth control, facial and cochlear nerve outcome - preliminary results.

<b>Introduction:</b> The choice of treatment of vestibular schwannoma (VS) depends on several factors, including the tumor size, the patient's age and overall health, and the presence and severity of symptoms.<b>Aim:</b> The aim of the study was to assess the effectiveness of intentional subtotal resection (STR) of tumor followed by Gamma Knife surgery (GKS) in patients with larger VS (Koos 3 and 4).<b>Materials and methods:</b> The retrospective analysis was performed on 18 patients. Data of VS volumes measured in MRI, the facial nerve function assessed in the House-Brackmann scoring system (HB), and the results of audiological examination expressed on the Gardner-Robertson scale (GR) were collected preoperatively, postoperatively, and post-GKS.<b>Results:</b> Preoperatively, the main symptom was hearing loss observed in 13 out of 18 patients. The facial nerve function was assessed as HB 1 in 16, whereas HB 2 in 2 patients. The mean volume of the tumor in the initial MRI amounted to 16.81 cm³ . Postoperatively, the facial nerve was assessed as HB 1 or 2 in 16, whereas HB 3 in 2 patients. Serviceable hearing was presented by only 4 persons. The Mean diameter of the tumor after subtotal surgery amounted to 3.16 cm³ , 1.83 cm³ after GKS, and 1.58 cm³ at the last follow-up. The facial nerve function and hearing level remained the same as before GKS in all patients.<b>Conclusions:</b> STR followed by GKS can be a safe and effective method of treatment of large VS concerning the functional outcome of the facial nerve and the tumor volume growth control.

Planned Subtotal Resection following Stereotactic Radiosurgery of Koos 3 and 4 Vestibular Schwannomas.

Background/Objectives: Surgical resection of medium to large vestibular schwannomas (VSs, Koos grade 3 and 4) is a widely used approach, although stereotactic radiosurgery (SRS) is increasingly proposed as initial treatment. The quality of life-centered approach is challenged in cases where tumor growth control cannot be achieved with SRS, thus necessitating salvage surgery. We present a series of eight consecutive patients who required surgery due to continued tumor growth after SRS. Methods: Of the 146 patients with VS grades 3 and 4 initially treated with SRS, only eight patients (mean age, 54 ± 7.2 years; range, 42-63 years) required subsequent surgery. Their mean tumor volume was 9.9 ± 3.2 cm3. The mean time from SRS to first tumor progression and planned subtotal resection was 23 ± 5.9 months and 45 ± 17.5 months, respectively. SRS was not performed after the surgery in favor of a "wait and rescan" approach. Tumor residue was monitored on follow-up magnetic resonance imaging. In all patients, tumor growth control after planned subtotal resection was maintained at 63 ± 19.8 months. Results: None of the 146 patients had serious complications after SRS. In the eight patients who required surgery, tumor growth between 22% and 212% (mean, 4 cm3) was reported within 26 to 84 months after SRS. Before salvage surgery, they scored 1 point on the House-Brackmann scale. Subtotal excision was performed, and VIIth nerve function was preserved in all patients. At 63 ± 19.8 months, 3 patients had a House-Brackmann score of 1, four patients had a score of 2, and one patient had a score of 3. Conclusions: Surgical excision of medium to large VS after SRS can be relatively safe, provided that a quality of life-centered approach of subtotal resection is used.

Outcomes and Prognostic Factors in the Treatment of Intracanalicular Vestibular Schwannomas Using Gamma Knife Stereotactic Radiation.

BACKGROUND: No gold standard has been developed for the therapy of intracanalicular vestibular schwannomas (IVS). Options for treatment include a conservative approach, microsurgery, or radiosurgery. Although the efficacy of these treatment has been well-documented, little is known about the determinants of outcome in IVSs following radiosurgery. Therefore, we examined the results in relation to age, gender, tumor volume, distance to fundus, microcyst existence, and radiosensitivity in this group. In addition, we investigated possible predictors of facial nerve function and hearing preservation. METHODS: Ninety-four patients with unilateral IVS were included in the evaluation (52 women and 42 males). The patients were separated into younger and older age groups based on their median age (55 years). The median IVS volume was 138 mm3, microcysts were identified in 16 tumors, and 63 tumors were adjacent to the fundus. The data were analyzed using Statistica software package ver. 13.3. RESULTS: At final follow-up, a statistically significant decrease in tumor volume and no statistically significant decline in hearing were noted, but no differences between age groups were found. The sex had no effect on overall tumor growth control, facial nerve preservation, or hearing preservation. Localization of IVS close to the fundus and the presence of tumor microcysts had no effect on the control of tumor growth, preservation of hearing, and sparing of facial nerve following radiosurgery. Cochlear dose had no influence on hearing preservation. Higher tumor volume was associated with its pseudoprogression during early follow-up and a greater risk of hearing loss. CONCLUSIONS: Age, sex, tumor volume, proximity to the fundus, and the existence of a microcyst were not predictive of radiosensitivity nor preservation of facial nerve function and hearing, based on the findings. There was no effect of cochlear dose on hearing. Initial greater tumor volume was associated with an increased probability of tumor pseudoprogression.

SARS-CoV-2 infection activating a novel variant of the NOTCH3 gene and subsequently causing development of CADASIL.

Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL). Material and methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before. Results: Furthermore, after subjecting the patient's close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation. Conclusions: It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient's genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19.

Accuracy of transcranial colour-coded sonography in the diagnosis of anterior cerebral artery vasospasm.

BACKGROUND AND PURPOSE: Transcranial colour-coded sonography (TCCS) has been proven to be a method of high performance in the diagnosis of spasm of the middle cerebral artery (MCA). Relevant data concerning the anterior cerebral artery (ACA) varies amongst studies. The aim of this study was to assess the performance of TCCS in the diagnosis of spasm affecting the ACA. MATERIAL AND METHODS: Ninety-two patients (39 women and 53 men, age 51 ± 12.1 years) were examined using TCCS before cerebral angiography. Of 184 examined ACAs, only 133 arteries could be visualized due to insufficiency of the temporal acoustic window. Therefore, only 15 out of 25 arteries in which vasospasm was diagnosed with angiography (by two neuroradiologists not informed about the sonographic findings) could be included in the analysis. Receiver operating characteristic (ROC) curves were constructed for specific blood flow velocities: peak systolic (PSV), mean (M) and end-diastolic (EDV). The area under the ROC curve was used to measure the overall diagnostic performance of TCCS. RESULTS: The area under the ROC curve for PSV was 0.83, which indicates good performance. The PSV threshold of 98 cm/s corresponded to maximum accuracy and was associated with 71% sensitivity vs. 88% specificity. Average systolic blood flow velocity in the vessels with vasospasm was 129 cm/s, whereas in unaffected vessels it was 76 cm/s. CONCLUSIONS: The accuracy of TCCS in the diagnosis of ACA spasm is relatively high - the value of the area under the ROC amounts to 0.83. PSV performs best and the threshold of 98 cm/s is associated with an optimal trade-off between sensitivity and specificity.

Early surgical removal of migrated coil/stent after failed embolization of intracranial aneurysm.

OBJECT: Distal coil or stent migration is a rare, but potentially morbid complication of intracranial aneurysm embolization. At present, there is no established standard of surgical evacuation of displaced material-in particular, there is no consensus on the optimum time for such intervention. The authors report their positive experiences with an ultra-early surgical evacuation of 2 migrated coils and a flow-diverter stent. METHODS: Uncontrolled coil or stent migration occurred in 3 (0.75%) of approximately 400 patients treated between 1999 and 2012 in the authors' institution. In all 3 cases, the materials moved from their intended position to the middle cerebral artery (MCA). Surgical evacuation was started immediately (within half an hour) after a futile attempt of removing them via intraarterial route, under the same anesthesia and with no active reversal of heparinization. RESULTS: No excessive bleeding was observed. Displaced coils were extracted through an incision of a branch of MCA-the anterior temporal artery, the stent was removed through a direct incision of MCA. Recombinant tissue plasminogen activator (rtPA) was injected to the stem of the internal carotid artery toward the end of the procedure, with no discernible adverse effects. Two patients were discharged with no deficit (Glasgow Outcome Scale [GOS] Score 5); the other patient was conscious with mild hemiparesis (GOS Score 4) at discharge. CONCLUSIONS: The experiences of these 3 cases suggest that immediate removal of a migrated stent/coil is feasible and may be effective. Indirect access to the MCA through its branch helps to shorten the time of temporary clipping of the artery to a minimum. Maintaining active heparinization and direct intraarterial injection of rtPA are helpful in promoting blood flow in the MCA.