The response of the blood-brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH. Supporting some of these beneficial cascades while attenuating the major pathophysiological pathways might be decisive in inhibiting the negative impact of bleeding in the subarachnoid space. In this review, we attempt a comprehensive overview of the current knowledge on the molecular and cellular changes in the BBB following SAH and their possible modulation by various drugs and substances.

• Klíčová slova
• Blood–brain barrier, Neuroinflammation, Neuronal injury, Neurovascular unit, Subarachnoid hemorrhage, Subarachnoid hemorrhage treatment,
• MeSH
• endoteliální buňky metabolismus   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• ischemie mozku * metabolismus   MeSH
• mikroglie MeSH
• modely nemocí na zvířatech MeSH
• subarachnoidální krvácení * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.

• Klíčová slova
• Subarachnoid hemorrhage, analgesic drugs, hydrocephalus, metamizole, patient outcome,
• MeSH
• analgetika terapeutické užití   aplikace a dávkování   MeSH
• antiflogistika nesteroidní * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• hydrocefalus etiologie   MeSH
• ischemie mozku farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metamizol * terapeutické užití   aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• subarachnoidální krvácení * farmakoterapie   komplikace   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• analgetika MeSH
• antiflogistika nesteroidní * MeSH
• metamizol * MeSH

BACKGROUND: In Africa, no cerebral aneurysm treatment guidelines exist. Epidemiology, management, and outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understood, with many underdiagnosed cases. Muhimbili Orthopaedic and Neurosurgery Institute (MOI) is the only neurosurgical referral center in Tanzania. The aim of this study is to describe the current aSAH management with regional outcomes and limitations. METHODS: Patients with aSAH confirmed by computed tomography/magnetic resonance angiography between February 2019 and June 2021 were retrospectively studied. The analyzed parameters included demographics, clinical/radiologic characteristics, injury characteristics, and the modified Rankin Scale (mRS) score. RESULTS: In total, 22 patients, with a female/male ratio of 1.4 and a median age of 54 years (interquartile range [IQR], 47.2-63 years) harboring 24 aneurysms were analyzed. Thirteen patients (59.1%) paid out of pocket. The median distance traveled by patients was 537 km (IQR, 34.7-635 km). The median time between admission and treatment was 12 days (IQR, 3.2-39 days). The most common symptoms were headache (n = 20; 90.9%) and high blood pressure (n = 10; 45.4%). Nine patients (40.9%) had Fisher grade 1 and 12 (54.5%) World Federation of Neurosurgical Societies grade I. The most common aneurysms were of the middle cerebral artery (7/29.2%). Fourteen patients (63.6%) underwent clipping; of those, only 4 (28.6%) were operated on within 72 hours. Mortality was 62.5% in the nonsurgical group. Among clipped patients, 78.6% showed favorable outcomes, with no mortality. Endovascular treatment is not available in Tanzania. CONCLUSIONS: To our best knowledge, this is the first study highlighting aSAH management in Tanzania, with its assets and shortcomings. Our data show pertinent differences among international treatment guidelines, with the resultant outcomes, such as high preoperative mortality resulting from delayed/postponed treatment. Regional difficult circumstances notwithstanding, our long-term goal is to significantly improve the overall management of aSAH in Tanzania.

• Klíčová slova
• Diagnosis, Intracranial aneurysm, Management, Subarachnoid hemorrhage, Tanzania,
• MeSH
• intrakraniální aneurysma * chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurochirurgie * MeSH
• ortopedie * MeSH
• retrospektivní studie MeSH
• subarachnoidální krvácení * diagnostické zobrazování   chirurgie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Tanzanie epidemiologie   MeSH

BACKGROUND: Evaluating the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) who may be at risk of poor outcomes using grading systems is one way to make a better decision on treatment for these patients. This study aimed to compare the accuracy of the modified World Federation of Neurosurgical Societies (WFNS), WFNS, and Hunt and Hess (H&H) Grading Scales in predicting the outcomes of patients with aSAH. METHODS: From August 2019 to June 2021, we conducted a multicenter prospective cohort study on adult patients with aSAH in three central hospitals in Hanoi, Vietnam. The primary outcome was the 90-day poor outcome, measured by a score of 4 (moderately severe disability) to 6 (death) on the modified Rankin Scale (mRS). We calculated the areas under the receiver operator characteristic (ROC) curve (AUROCs) to determine how well the grading scales could predict patient prognosis upon admission. We also used ROC curve analysis to find the best cut-off value for each scale. We compared AUROCs using Z-statistics and compared 90-day mean mRS scores among intergrades using the pairwise multiple-comparison test. Finally, we used logistic regression to identify factors associated with the 90-day poor outcome. RESULTS: Of 415 patients, 32% had a 90-day poor outcome. The modified WFNS (AUROC: 0.839 [95% confidence interval, CI: 0.795-0.883]; cut-off value≥2.50; PAUROC<0.001), WFNS (AUROC: 0.837 [95% CI: 0.793-0.881]; cut-off value≥3.5; PAUROC<0.001), and H&H scales (AUROC: 0.836 [95% CI: 0.791-0.881]; cut-off value≥3.5; PAUROC<0.001) were all good at predicting patient prognosis on day 90th after ictus. However, there were no significant differences between the AUROCs of these scales. Only grades IV and V of the modified WFNS (3.75 [standard deviation, SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), WFNS (3.75 [SD: 2.46] vs 5.24 [SD: 1.68], p = 0.026, respectively), and H&H scales (2.96 [SD: 2.60] vs 4.97 [SD: 1.87], p<0.001, respectively) showed a significant difference in the 90-day mean mRS scores. In multivariable models, with the same set of confounding variables, the modified WFNS grade of III to V (adjusted odds ratio, AOR: 9.090; 95% CI: 3.494-23.648; P<0.001) was more strongly associated with the increased risk of the 90-day poor outcome compared to the WFNS grade of IV to V (AOR: 6.383; 95% CI: 2.661-15.310; P<0.001) or the H&H grade of IV to V (AOR: 6.146; 95% CI: 2.584-14.620; P<0.001). CONCLUSIONS: In this study, the modified WFNS, WFNS, and H&H scales all had good discriminatory abilities for the prognosis of patients with aSAH. Because of the better effect size in predicting poor outcomes, the modified WFNS scale seems preferable to the WFNS and H&H scales.

• MeSH
• dospělí MeSH
• hospitalizace MeSH
• lidé MeSH
• nemocnice MeSH
• odds ratio MeSH
• prospektivní studie MeSH
• subarachnoidální krvácení * diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Clinically symptomatic vasospasm leading to delayed ischemic neurological deficits occurs in up to 30% of patients with subarachnoid hemorrhage (SAH). Vasospasm can result in a serious decline in clinical conditions of patients with SAH, yet the algorithm for vasospasm treatment and prevention remains unclear. Intra-arterial administration of vasodilators is one of the modalities used for vasospasm therapy. METHODS: Over the last 7 years, we have treated 27 female and 7 male patients with vasospasm using intra-arterial administration of either nimodipine or milrinone; all had suffered aneurysm rupture. Of these patients, 28 were treated surgically (clip), and 6 patients had their aneurysm coiled. Spasmolytics were applied from day 2 to day 18 after rupture. RESULTS: Of the 53 procedures, angiographic improvement was documented in 92% of cases with a mean flow velocity decrease of 65 cm/s. Brain metabolism changes were monitored after the procedure. The highest level of immediate clinical improvement was observed in conscious patients with a focal neurological deficit (aphasia, hemiparesis). Overall clinical outcomes (Glasgow outcome scale, GOS) were as follows: GOS 5 (12 patients), GOS 4 (5 patients), GOS 3 (5 patients), GOS 2 (6 patients), and GOS 1 (6 patients). CONCLUSIONS: Intra-arterial administration of spasmolytics is a safe and potent method of vasospasm treatment. It is most effective when applied to conscious patients with a focal deficit. For unconscious patients, its therapeutic benefits are inconclusive. Patients in severe clinical states would further require use of other diagnostic tools such as multimodal brain monitoring to complement vasospasm therapy.

• Klíčová slova
• Angiography, Cerebral vasospasm, Microdialysis, Milrinone, Nimodipine, Outcome, Spasmolytics, Transcranial dopplerometry,
• MeSH
• angioplastika škodlivé účinky   metody   MeSH
• dospělí MeSH
• intraarteriální infuze škodlivé účinky   MeSH
• intrakraniální vazospazmus farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nimodipin aplikace a dávkování   terapeutické užití   MeSH
• subarachnoidální krvácení farmakoterapie   MeSH
• vazodilatancia aplikace a dávkování   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nimodipin MeSH
• vazodilatancia MeSH

There are reports that in patients with aSAH (aneurysmal subarachnoid hemorrhage), LTF (lamina terminalis fenestration) reduces the rate of shunt-needed hydrocephalus via facilitation of CSF (cerebrospinal fluid) dynamic, diminished leptomeningeal inflammation, and decreased subarachnoid fibrosis. Regarding the conflicting results, this study was conducted to evaluate the effects of LTF on decreased shunt-needed hydrocephalus in patients with aSAH. A cross-sectional retrospective study was carried out to survey all patients with confirmed aSAH operated from March 2011 to September 2016 in an academic vascular center (Rasool Akram Hospital in Tehran, Iran). Of a total of 151 patients, 72 patients were male and 79 were female. The mean age of the participants was 51 years. A transiently CSF diversion (EVD - external ventricular drainage) was performed (the acute hydrocephalus rate) on 21 patients (13.9%). In 36 patients (23.8%), aneurysm occlusion with LTF and in 115 patients (76.2%) only aneurysm occlusion surgery was performed. In hydrocephalus follow-up after surgery, 13 (12%) patients needed shunt insertion (the rate of shunt-needed hydrocephalus). The statistical analysis demonstrated no significant relation between LTF and shunt-needed hydrocephalus. Confirmation of the hypothesis that LTF may decrease the rate of shunt-needed hydrocephalus can significantly decrease morbidity, mortality, and treatment costs of shunting (that is a simple, but a potentially dangerous procedure). So, it is advised to plan and perform an RCT (randomized controlled trial) that can remove the confounding factors, match the groups, and illustrate the exact effect of LTF on shunt-needed hydrocephalus.

• Klíčová slova
• Acute hydrocephalus, Aneurysmal subarachnoid hemorrhage, Lamina terminalis fenestration, Shunt-needed hydrocephalus, Ventriculostomy,
• MeSH
• hydrocefalus * etiologie   chirurgie   MeSH
• hypothalamus chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• subarachnoidální krvácení * komplikace   chirurgie   MeSH
• ventrikulostomie * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Írán MeSH

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.

• Klíčová slova
• Aneurysmal subarachnoid hemorrhage, Cerebral ischemia, Non-steroidal anti-inflammatory drugs, Vasospasms,
• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• intrakraniální vazospazmus farmakoterapie   etiologie   patofyziologie   MeSH
• ischemie mozku farmakoterapie   etiologie   patofyziologie   MeSH
• lidé MeSH
• nimodipin terapeutické užití   MeSH
• randomizované kontrolované studie jako téma metody   MeSH
• subarachnoidální krvácení komplikace   farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• nimodipin MeSH

OBJECTIVE: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated. RESULTS: A total of 409 patients were randomized between February 2019 and May 2022 across 74 international sites. Three patients did not start study treatment and were not included in the analysis set. The occurrence of clinical deterioration due to DCI was 15.8% (32/202 patients) in the clazosentan group and 17.2% (35/204 patients) in the placebo group, and the difference was not statistically significant (relative risk reduction [RRR] 7.2%, 95% CI -42.6% to 39.6%, p = 0.734). A nonsignificant RRR of 34.1% (95% CI -21.3% to 64.2%, p = 0.177) was observed in clinically relevant cerebral infarcts treated with clazosentan (7.4%, 15/202) versus placebo (11.3%, 23/204). Rescue therapy was less frequently needed for patients treated with clazosentan compared to placebo (10.4%, 21/202 vs 18.1%, 37/204; RRR 42.6%, 95% CI 5.4%-65.2%). A nonsignificant relative risk increase of 25.4% (95% CI -10.7% to 76.0%, p = 0.198) was reported in the risk of poor GOSE and mRS scores with clazosentan (24.8%, 50/202) versus placebo (20.1%, 41/204) at week 12 post-aSAH. Treatment-emergent adverse events were similar to those reported previously. CONCLUSIONS: Clazosentan administered for up to 14 days at 15 mg/hour had no significant effect on the occurrence of clinical deterioration due to DCI. Clinical trial registration no.: NCT03585270 (ClinicalTrials.gov) EU clinical trial registration no.: 2018-000241-39 (clinicaltrialsregister.eu).

• Klíčová slova
• aneurysm, cerebral ischemia, cerebral vasospasm, clazosentan, endothelin-1, subarachnoid hemorrhage, vascular disorders,
• MeSH
• dioxany * terapeutické užití   škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• intrakraniální vazospazmus etiologie   prevence a kontrola   farmakoterapie   diagnostické zobrazování   MeSH
• ischemie mozku * prevence a kontrola   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• pyridiny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• pyrimidiny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• senioři MeSH
• subarachnoidální krvácení * komplikace   diagnostické zobrazování   MeSH
• sulfonamidy * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• tetrazoly * terapeutické užití   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• clazosentan MeSH Prohlížeč
• dioxany * MeSH
• pyridiny * MeSH
• pyrimidiny * MeSH
• sulfonamidy * MeSH
• tetrazoly * MeSH

OBJECTIVE: The aim of this study was to evaluate the effect of preventive and therapeutic use of subarachnoid sodium nitroprusside (SNP) administration in patients with non-traumatic subarachnoid haemorrhage (SAH). METHODS: All consecutive adult patients admitted in the period 2000-2003 with SAH, Hunt-Hess grade I-IV, indicated for neurosurgical intervention, were enrolled in the study. In the postoperative period they were treated with mechanical ventilation and triple H protocol with nimodipine. Subarachnoid preventive SNP was administred in initial dose of 1 mg by catheter inserted into basal cisterns during the neurosurgical procedure. The timing of following dosage was directed by the changes of respiratory parameters of brain tissue in the region of interest by multiparameter sensor (Codman Neurotrend) and findings of blood flow velocity on the level of circle of Willis were measured by transcranial doppler ultrasonography (TCD). RESULTS: 17 patients were enrolled to study. All patients survived. No brain infarction developed. The increase blood flow velocity was found in three patients. CONCLUSION: Preventive subarachnoid use of SNP in combination with multimodal monitoring might be a possible preventive strategy. Its efficacy has to be proved on a greater group of patients in the future. The therapeutical use of SNP requires an increase in application rate.

• MeSH
• dospělí MeSH
• injekce intraventrikulární MeSH
• intrakraniální vazospazmus diagnóza   etiologie   prevence a kontrola   MeSH
• katetrizace metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nitroprusid aplikace a dávkování   MeSH
• senioři MeSH
• subarachnoidální krvácení komplikace   diagnóza   farmakoterapie   MeSH
• subarachnoidální prostor účinky léků   MeSH
• vazodilatancia aplikace a dávkování   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• nitroprusid MeSH
• vazodilatancia MeSH

Ruptured cerebral aneurysm is the most common cause of non-traumatic subarachnoid hemorrhage. Subsequent to this catastrophe, patients have usually evidence of severe headache with sudden onset, signs of meningeal irritation, and depression of consciousness. Difficulties in diagnosis arise when the clinical picture is not classical. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage is the leading cause of death and disability after aneurysm rupture. In the presence of a typical history and a normal CT scan, lumbar puncture should be performed with spectrophotometry analysis of the supernatant. After subarachnoid hemorrhage has been confirmed, four-vessel angiography should be performed as soon as possible. The surgical treatment of subarachnoid hemorrhage caused by ruptured aneurysm is the method of choice.

• MeSH
• intrakraniální aneurysma komplikace   diagnóza   MeSH
• lidé MeSH
• prasklé aneurysma komplikace   diagnóza   MeSH
• subarachnoidální krvácení diagnóza   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH