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Liu MZ, Dai XH, Zeng MT, Chen EQ. Clinical treatment of cryptococcal meningitis: an evidence-based review on the emerging clinical data. J Neurol 2024; 271:2960-2979. [PMID: 38289535 DOI: 10.1007/s00415-024-12193-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 01/07/2024] [Accepted: 01/13/2024] [Indexed: 05/30/2024]
Abstract
Cryptococcal meningitis (CM) is a fatal fungal central nervous system (CNS) infection caused by Cryptococcus infecting the meninges and/or brain parenchyma, with fever, headache, neck stiffness, and visual disturbances as the primary clinical manifestations. Immunocompromised individuals with human immunodeficiency virus (HIV) infection or who have undergone organ transplantation, as well as immunocompetent people can both be susceptible to CM. Without treatment, patients with CM may have a mortality rate of up to 100% after hospital admission. Even after receiving therapy, CM patients may still suffer from problems such as difficulty to cure, poor prognosis, and high mortality. Therefore, timely and effective treatment is essential to improve the mortality and prognosis of CM patients. Currently, the clinical outcomes of CM are frequently unsatisfactory due to limited drug choices, severe adverse reactions, drug resistance, etc. Here, we review the research progress of CM treatment strategies and discuss the suitable options for managing CM, hoping to provide a reference for physicians to select the most appropriate treatment regimens for CM patients.
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Affiliation(s)
- Mao-Zhu Liu
- Center of Infectious Diseases, West China Hospital, Sichuan University, No.37 Guo Xue Xiang, Wuhou District, Chengdu, 610041, China
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xin-Hua Dai
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ming-Tang Zeng
- Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, No.37 Guo Xue Xiang, Wuhou District, Chengdu, 610041, China.
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Simard JM, Wilhelmy B, Tsymbalyuk N, Shim B, Stokum JA, Evans M, Gaur A, Tosun C, Keledjian K, Ciryam P, Serra R, Gerzanich V. Brain Swelling versus Infarct Size: A Problematizing Review. Brain Sci 2024; 14:229. [PMID: 38539619 PMCID: PMC10968884 DOI: 10.3390/brainsci14030229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 02/21/2024] [Accepted: 02/24/2024] [Indexed: 05/16/2024] Open
Abstract
In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.
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Affiliation(s)
- J. Marc Simard
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
- Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Bradley Wilhelmy
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Natalya Tsymbalyuk
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Bosung Shim
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Jesse A. Stokum
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Madison Evans
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Anandita Gaur
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Cigdem Tosun
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Kaspar Keledjian
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Prajwal Ciryam
- Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Riccardo Serra
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
| | - Volodymyr Gerzanich
- Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.W.); (N.T.); (B.S.); (J.A.S.); (M.E.); (A.G.); (C.T.); (K.K.); (R.S.); (V.G.)
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain, which has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2020. OBJECTIVES To assess the benefits and harms of Cerebrolysin or Cerebrolysin-like agents for treating acute ischaemic stroke. SEARCH METHODS We searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, and LILACS in May 2022 and a number of Russian databases in June 2022. We also searched reference lists, ongoing trials registers, and conference proceedings. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing Cerebrolysin or Cerebrolysin-like agents started within 48 hours of stroke onset and continued for any length of time, with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Three review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, extracted data, and applied GRADE criteria to the evidence. MAIN RESULTS Seven RCTs (1773 participants) met the inclusion criteria of the review. In this update we added one RCT of Cerebrolysin-like agent Cortexin, which contributed 272 participants. We used the same approach for risk of bias assessment that was re-evaluated for the previous update: we added consideration of the public availability of study protocols and reported outcomes to the selective outcome reporting judgement, through identification, examination, and evaluation of study protocols. For the Cerebrolysin studies, we judged the risk of bias for selective outcome reporting to be unclear across all studies; for blinding of participants and personnel to be low in three studies and unclear in the remaining four; and for blinding of outcome assessors to be low in three studies and unclear in four studies. We judged the risk of bias for generation of allocation sequence to be low in one study and unclear in the remaining six studies; for allocation concealment to be low in one study and unclear in six studies; and for incomplete outcome data to be low in three studies and high in the remaining four studies. The manufacturer of Cerebrolysin supported three multicentre studies, either totally, or by providing Cerebrolysin and placebo, randomisation codes, research grants, or statisticians. We judged two studies to be at high risk of other bias and the remaining five studies to be at unclear risk of other bias. We judged the study of Cortexin to be at low risk of bias for incomplete outcome data and at unclear risk of bias for all other domains. All-cause death: Cerebrolysin or Cortexin probably result in little to no difference in all-cause death (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.41; 6 trials, 1689 participants; moderate-certainty evidence). None of the included studies reported on poor functional outcome, defined as death or dependence at the end of the follow-up period, early death (within two weeks of stroke onset), quality of life, or time to restoration of capacity for work. Only one study clearly reported on the cause of death: cerebral infarct (four in the Cerebrolysin and two in the placebo group), heart failure (two in the Cerebrolysin and one in the placebo group), pulmonary embolism (two in the placebo group), and pneumonia (one in the placebo group). Non-death attrition (secondary outcome): Cerebrolysin or similar peptide mixtures may result in little to no difference in non-death attrition, but the evidence is very uncertain, with a considerable level of heterogeneity (RR 0.72, 95% CI 0.38 to 1.39; 6 trials, 1689 participants; very low-certainty evidence). Serious adverse events (SAEs): Cerebrolysin probably results in little to no difference in the total number of people with SAEs (RR 1.16, 95% CI 0.81 to 1.66; 3 trials, 1335 participants; moderate-certainty evidence). This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38; 3 trials, 1335 participants; moderate-certainty evidence) and an increase in the total number of people with non-fatal SAEs (RR 2.39, 95% CI 1.10 to 5.23; 3 trials, 1335 participants; moderate-certainty evidence). In the subgroup of dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase was more prominent (RR 2.87, 95% CI 1.24 to 6.69; 2 trials, 1189 participants). Total number of people with adverse events: Cerebrolysin or similar peptide mixtures may result in little to no difference in the total number of people with adverse events (RR 1.03, 95% CI 0.92 to 1.14; 4 trials, 1607 participants; low-certainty evidence). AUTHORS' CONCLUSIONS Moderate-certainty evidence indicates that Cerebrolysin or Cerebrolysin-like peptide mixtures derived from cattle brain probably have no beneficial effect on preventing all-cause death in acute ischaemic stroke. Moderate-certainty evidence suggests that Cerebrolysin probably has no beneficial effect on the total number of people with serious adverse events. Moderate-certainty evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use.
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Affiliation(s)
- Liliya Eugenevna Ziganshina
- Centre for Knowledge Translation, Federal State Budgetary Educational Institution of Continuing Professional Education "Russian Medical Academy of Continuing Professional Education", The Ministry of Health of the Russian Federation (RMANPO), Moscow, Russian Federation
- Department of Pharmacology, Kazan State Medical University (KSMU), The Ministry of Health of the Russian Federation, Kazan, Russian Federation
- Department of General and Clinical Pharmacology, RUDN University named after Patrice Lumumba, Moscow, Russian Federation
| | - Tatyana Abakumova
- Department of Biochemistry, Biotechnology and Pharmacology, Kazan (Volga region) Federal University, Kazan, Russian Federation
| | - Dilyara Nurkhametova
- Centre for Knowledge Translation, Federal State Budgetary Educational Institution of Continuing Professional Education "Russian Medical Academy of Continuing Professional Education", The Ministry of Health of the Russian Federation (RMANPO), Moscow, Russian Federation
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Wang J, Wang R, Qin H, Zuo L. Impaired Kidney Function Portended a Bleak Prognosis for Surgically Treated Hypertensive Intracerebral Hemorrhage Patients. Ann Indian Acad Neurol 2023; 26:520-529. [PMID: 37970258 PMCID: PMC10645252 DOI: 10.4103/aian.aian_195_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 06/20/2023] [Accepted: 08/13/2023] [Indexed: 11/17/2023] Open
Abstract
Purpose Spontaneous intracerebral hemorrhage (ICH) cases caused by hypertension often have poor prognoses. The use of dehydrant agents, such as mannitol, is common to reduce intracranial pressure and alleviate cerebral edema, but they may also pose a risk of worsening kidney function. This study aimed to investigate the impact of impaired kidney function on the outcomes of surgically treated hypertensive ICH patients. Methods We conducted a retrospective analysis of a consecutive cohort of patients who underwent surgical intervention due to hypertension-related ICH at our institute between December 1, 2017, and January 31, 2022. Demographic, clinical, radiological, and prognostic data were collected. Patients were categorized into two groups based on 90-day mortality: group A [overall survival (OS) ≤3 months] and group B (OS >3 months). Survival analysis was performed to identify factors associated with poor outcomes. Results Among the 232 eligible patients, group A exhibited significantly impaired kidney function, as indicated by mean estimated glomerular filtration rate (eGFR) at admission, postoperative, 3-day postoperative, and 7-day postoperative time points (91.9, 82.5, 73.5, 75.2 ml/min/1.73 m²). In contrast, group B did not show significant changes in kidney function (mean eGFR for the corresponding time points: 108.1, 106.5, 111.5, 109.6 ml/min/1.73 m²). The 3-day postoperative eGFR showed the strongest predictive ability for assessing prognosis [areas under the curve (AUC): 0.617, 0.675, 0.737, 0.730]. Univariate and multivariate analyses identified low Glasgow Coma Scale (GCS) score (3-8), ventricle intrusion of hematomas, cardiac failure, larger hematoma volume, infection, and lower 3-day postoperative eGFR as adverse factors for survival. Conclusions Preserving kidney function is crucial for achieving favorable outcomes in hypertensive ICH cases. Impaired 3-day postoperative eGFR emerged as an independent risk factor for overall survival. Patients with cardiac failure, infection, and larger hematoma volume should receive careful management to improve outcomes.
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Affiliation(s)
- Jian Wang
- Department of Trauma Intensive Care Unit, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China
| | - Rui Wang
- Department of Trauma Intensive Care Unit, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China
| | - Hu Qin
- Department of Neurosurgery, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China
| | - Lei Zuo
- Department of Trauma Intensive Care Unit, First Affiliated Hospital, Xinjiang Medical University, Urumqi 830011, China
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Zhang L, Liao W, Huang Y, Wen Y, Chu Y, Zhao C. Global seaweed farming and processing in the past 20 years. FOOD PRODUCTION, PROCESSING AND NUTRITION 2022. [DOI: 10.1186/s43014-022-00103-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AbstractSeaweed has emerged as one of the most promising resources due to its remarkable adaptability, short development period, and resource sustainability. It is an effective breakthrough to alleviate future resource crises. Algal resources have reached a high stage of growth in the past years due to the increased output and demand for seaweed worldwide. Several aspects global seaweed farming production and processing over the last 20 years are reviewed, such as the latest situation and approaches of seaweed farming. Research progress and production trend of various seaweed application are discussed. Besides, the challenges faced by seaweed farming and processing are also analyzed, and the related countermeasures are proposed, which can provide advice for seaweed farming and processing. The primary products, extraction and application, or waste utilization of seaweed would bring greater benefits with the continuous development and improvement of applications in various fields.
Graphical Abstract
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Kim HS, Lee JY, Jung JW, Lee KH, Kim MJ, Park SB. Is mannitol combined with furosemide a new treatment for refractory lymphedema? A case report. World J Clin Cases 2021; 9:8804-8811. [PMID: 34734059 PMCID: PMC8546829 DOI: 10.12998/wjcc.v9.i29.8804] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 07/30/2021] [Accepted: 09/08/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mannitol is a hyperosmolar agent and the combination of mannitol and furosemide is a widely used treatment for intracranial pressure control. Considering the hypertonic properties of mannitol to move water out of intracellular spaces, we hypothesized that mannitol combined with furosemide could relieve focal tissue swelling in refractory lymphedema.
CASE SUMMARY A 90-year-old female had been diagnosed with intracranial hemorrhage and received a combination of mannitol and furosemide for intracranial pressure control. Independent of the intracranial hemorrhage, she had refractory lymphedema of the left lower extremity since 1998. Remarkably, after receiving the mannitol and furosemide, the patient’s lower extremity lymphedema improved dramatically. After the mannitol and furosemide were discontinued, the lymphedema worsened in spite of complete decongestive therapy (CDT) and intermittent pneumatic compression treatment (IPC). To identify the presumed effect of mannitol and furosemide on the lymphedema, these agents were resumed, and the lymphedema improved again.
CONCLUSION The present case raises the possibility that a combination of mannitol and furosemide might be considered another effective therapeutic option for refractory lymphedema when CDT and IPC are ineffective.
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Affiliation(s)
- Hyeon Seong Kim
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Jae Young Lee
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Ji Won Jung
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Kyu Hoon Lee
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Mi Jung Kim
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
| | - Si-Bog Park
- Department of Rehabilitation Medicine, Hanyang University Hospital, Seoul 04763, South Korea
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Lee CY, Park SH, Lim HY, Jang SG, Park KJ, Kim DS, Kim JH, Cho JY. In vivo anti-inflammatory effects of Prasiola japonica ethanol extract. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Craparo EF, Cabibbo M, Conigliaro A, Barreca MM, Musumeci T, Giammona G, Cavallaro G. Rapamycin-Loaded Polymeric Nanoparticles as an Advanced Formulation for Macrophage Targeting in Atherosclerosis. Pharmaceutics 2021; 13:pharmaceutics13040503. [PMID: 33916918 PMCID: PMC8067637 DOI: 10.3390/pharmaceutics13040503] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/02/2021] [Accepted: 04/02/2021] [Indexed: 12/20/2022] Open
Abstract
Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by mannitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) graft copolymer. To obtain nanoparticles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdia-PC), was added to the starting organic phase. The chemical–physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdia-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug.
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Affiliation(s)
- Emanuela Fabiola Craparo
- Department of Biological, Chemical and Pharmaceutical Science and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy; (M.C.); (G.G.)
- Correspondence: (E.F.C.); (G.C.); Tel.: +39-091-23891937 (E.F.C.); +39-091-23891931 (G.C.)
| | - Marta Cabibbo
- Department of Biological, Chemical and Pharmaceutical Science and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy; (M.C.); (G.G.)
| | - Alice Conigliaro
- Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), University of Palermo, Via Divisi 83, 90133 Palermo, Italy; (A.C.); (M.M.B.)
| | - Maria Magdalena Barreca
- Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), University of Palermo, Via Divisi 83, 90133 Palermo, Italy; (A.C.); (M.M.B.)
| | - Teresa Musumeci
- Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, Via Santa Sofia 64, 95125 Catania, Italy;
| | - Gaetano Giammona
- Department of Biological, Chemical and Pharmaceutical Science and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy; (M.C.); (G.G.)
| | - Gennara Cavallaro
- Department of Biological, Chemical and Pharmaceutical Science and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy; (M.C.); (G.G.)
- Correspondence: (E.F.C.); (G.C.); Tel.: +39-091-23891937 (E.F.C.); +39-091-23891931 (G.C.)
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Mohney N, Alkhatib O, Koch S, O'Phelan K, Merenda A. What is the Role of Hyperosmolar Therapy in Hemispheric Stroke Patients? Neurocrit Care 2021; 32:609-619. [PMID: 31342452 DOI: 10.1007/s12028-019-00782-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The role of hyperosmolar therapy (HT) in large hemispheric ischemic or hemorrhagic strokes remains a controversial issue. Past and current stroke guidelines state that it represents a reasonable therapeutic measure for patients with either neurological deterioration or intracranial pressure (ICP) elevations documented by ICP monitoring. However, the lack of evidence for a clear effect of this therapy on radiological tissue shifts and clinical outcomes produces uncertainty with respect to the appropriateness of its implementation and duration in the context of radiological mass effect without clinical correlates of neurological decline or documented elevated ICP. In addition, limited data suggest a theoretical potential for harm from the prophylactic and protracted use of HT in the setting of large hemispheric lesions. HT exerts effects on parenchymal volume, cerebral blood volume and cerebral perfusion pressure which may ameliorate global ICP elevation and cerebral blood flow; nevertheless, it also holds theoretical potential for aggravating tissue shifts promoted by significant interhemispheric ICP gradients that may arise in the setting of a large unilateral supratentorial mass lesion. The purpose of this article is to review the literature in order to shed light on the effects of HT on brain tissue shifts and clinical outcome in the context of large hemispheric strokes, as well as elucidate when HT should be initiated and when it should be avoided.
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Affiliation(s)
- Nathan Mohney
- Department of Neurology, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
- Department of Neurosurgery, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
| | - Omar Alkhatib
- Department of Neurology, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
- Department of Neurosurgery, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
| | - Sebastian Koch
- Department of Neurology, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
- Department of Neurosurgery, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
| | - Kristine O'Phelan
- Department of Neurology, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
- Department of Neurosurgery, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA
| | - Amedeo Merenda
- Department of Neurology, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA.
- Department of Neurosurgery, University of Miami Health System, 1120 NW 14th Street, Miami, FL, 33136, USA.
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Zhang G, Pan C, Zhang P, McBride DW, Tang Y, Wu G, Tang Z. Precision of minimally invasive surgery for intracerebral hemorrhage treatment. BRAIN HEMORRHAGES 2020. [DOI: 10.1016/j.hest.2020.11.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
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Li J, Gu Y, Li G, Wang L, Cheng X, Wang M, Zhao M. The Role of Hypothermia in Large Hemispheric Infarction: A Systematic Review and Meta-Analysis. Front Neurol 2020; 11:549872. [PMID: 33192981 PMCID: PMC7653189 DOI: 10.3389/fneur.2020.549872] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 09/18/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Hypothermia is used in the treatment of large hemispheric infarction (LHI); however, its role in outcomes for LHI patients remains ambiguous. This systematic review and meta-analysis was conducted to evaluate the effect of hypothermia on the outcomes of LHI patients. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China Biological Medicine Database, and clinical trials registers before September 21, 2018, and then scanned the reference lists. Randomized controlled trials that compared hypothermia with normothermia in LHI patients were included. Primary outcomes that we reviewed were mortality and neurological outcome. Adverse events during treatment were defined as secondary outcomes. We performed a meta-analysis to calculate pooled risk ratios (RRs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) using fixed-effect models. Results: Three randomized controlled trials involving 131 participants were included. No statistically significant association was revealed between hypothermia and mortality (RR, 1.12; 95% CI, 0.76-1.65). There was significant association between hypothermia and good neurological outcome as assessed by modified Rankin Scale score (mRS of 0-3) of survivors (RR, 2.09; 95% CI, 1.14-3.82), and with neurological outcome by mRS (SMD, -0.54; 95% CI, -1.07 to -0.01). However, significant associations were found between hypothermia and gastrointestinal bleeding, gastric retention, electrolyte derangement, and shivering. No significant differences were detected in the incidence of developing herniation in the rewarming process, pneumonia, cardiac arrhythmia, hemorrhagic transformation, hyperglycemia, hypotension, acute kidney injury, and venous thrombotic events in LHI patients who underwent hypothermia compared with those who had normothermia. Conclusions: This meta-analysis suggested that hypothermia was not associated with mortality in LHI patients. However, it was associated with the improvement of neurological outcome, but with a higher risk of adverse events during treatment. Future studies are needed to demonstrate the efficacy and safety of hypothermia for LHI. The protocol for this systematic review was obtained from PROSPERO (registration number: CRD42018111761).
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Affiliation(s)
- Jing Li
- Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Yanghui Gu
- Department of Cardiology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China
| | - Gang Li
- Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Lixin Wang
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaobin Cheng
- Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Min Wang
- Department of Intensive Care Unit, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
- Hubei Province Academy of Traditional Chinese Medicine, Wuhan, China
| | - Min Zhao
- Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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12
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from porcine brain that has potential neuroprotective properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. This is an update of a review first published in 2010 and last updated in 2017. OBJECTIVES To assess the benefits and harms of Cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian databases in October 2019. We also searched reference lists, ongoing trials registers, and conference proceedings. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing Cerebrolysin, started within 48 hours of stroke onset and continued for any length of time, with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Two review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, extracted data, and applied GRADE criteria to the evidence. MAIN RESULTS Seven RCTs (1601 participants) met the inclusion criteria of the review. In this update we re-evaluated risk of bias through identification, examination, and evaluation of study protocols and judged it to be low, unclear, or high across studies: unclear for all domains in one study, and unclear for selective outcome reporting across all studies; low for blinding of participants and personnel in four studies and unclear in the remaining three; low for blinding of outcome assessors in three studies and unclear in four studies. We judged risk of bias to be low in two studies and unclear in the remaining five studies for generation of allocation sequence; low in one study and unclear in six studies for allocation concealment; and low in one study, unclear in one study, and high in the remaining five studies for incomplete outcome data. The manufacturer of Cerebrolysin supported four multicentre studies, either totally, or by providing Cerebrolysin and placebo, randomisation codes, research grants, or statisticians. We judged three studies to be at high risk of other bias and the remaining four studies to be at unclear risk of other bias. All-cause death: we extracted data from six trials (1517 participants). Cerebrolysin probably results in little to no difference in all-cause death: risk ratio (RR) 0.90, 95% confidence interval (CI) 0.61 to 1.32 (6 trials, 1517 participants, moderate-quality evidence). None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset), or time to restoration of capacity for work and quality of life. Only one trial clearly reported on the cause of death: cerebral infarct (four in the Cerebrolysin and two in the placebo group), heart failure (two in the Cerebrolysin and one in the placebo group), pulmonary embolism (two in the placebo group), and pneumonia (one in the placebo group). Serious adverse events (SAEs): Cerebrolysin probably results in little to no difference in the total number of people with SAEs (RR 1.15, 95% CI 0.81 to 1.65, 4 RCTs, 1435 participants, moderate-quality evidence). This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the total number of people with non-fatal SAEs (RR 2.15, 95% CI 1.01 to 4.55, P = 0.047, 4 trials, 1435 participants, moderate-quality evidence). In the subgroup of dosing schedule 30 mL for 10 days (cumulative dose 300 mL), the increase was more prominent: RR 2.86, 95% CI 1.23 to 6.66, P = 0.01 (2 trials, 1189 participants). Total number of people with adverse events: four trials reported on this outcome. Cerebrolysin may result in little to no difference in the total number of people with adverse events: RR 0.97, 95% CI 0.85 to 1.10, P = 0.90, 4 trials, 1435 participants, low-quality evidence. Non-death attrition: evidence from six trials involving 1517 participants suggests that Cerebrolysin results in little to no difference in non-death attrition, with 96 out of 764 Cerebrolysin-treated participants and 117 out of 753 placebo-treated participants being lost to follow-up for reasons other than death (very low-quality evidence). AUTHORS' CONCLUSIONS Moderate-quality evidence indicates that Cerebrolysin probably has little or no beneficial effect on preventing all-cause death in acute ischaemic stroke, or on the total number of people with serious adverse events. Moderate-quality evidence also indicates a potential increase in non-fatal serious adverse events with Cerebrolysin use.
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Affiliation(s)
- Liliya Eugenevna Ziganshina
- Cochrane Russia, Kazan, Russian Federation
- Department of Pharmacology, Kazan State Medical University, Kazan, Russian Federation
| | - Tatyana Abakumova
- Department of Biochemistry, Biotechnology and Pharmacology, Kazan (Volga region) Federal University, Kazan, Russian Federation
| | - Charles Hv Hoyle
- Cochrane Russia, Kazan, Russian Federation
- Deputy Editor-in-Chief, Kazan Medical Journal, Kazan, Russian Federation
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13
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Cook AM, Morgan Jones G, Hawryluk GWJ, Mailloux P, McLaughlin D, Papangelou A, Samuel S, Tokumaru S, Venkatasubramanian C, Zacko C, Zimmermann LL, Hirsch K, Shutter L. Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients. Neurocrit Care 2020; 32:647-666. [PMID: 32227294 PMCID: PMC7272487 DOI: 10.1007/s12028-020-00959-7] [Citation(s) in RCA: 204] [Impact Index Per Article: 40.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. METHODS The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. RESULTS The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. CONCLUSION The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.
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Affiliation(s)
- Aaron M Cook
- UK Healthcare, University of Kentucky College of Pharmacy, Lexington, KY, USA.
| | | | | | | | | | | | - Sophie Samuel
- Memorial Hermann-Texas Medical Center, Houston, TX, USA
| | - Sheri Tokumaru
- The Daniel K. Inouye College of Pharmacy | University of Hawaii at Hilo, Honolulu, HI, USA
| | | | - Christopher Zacko
- Penn State University Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | | | - Karen Hirsch
- Stanford University Medical Center, Stanford, CA, USA
| | - Lori Shutter
- University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
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14
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Schreibman DL, Hong CM, Keledjian K, Ivanova S, Tsymbalyuk S, Gerzanich V, Simard JM. Mannitol and Hypertonic Saline Reduce Swelling and Modulate Inflammatory Markers in a Rat Model of Intracerebral Hemorrhage. Neurocrit Care 2019; 29:253-263. [PMID: 29700692 DOI: 10.1007/s12028-018-0535-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Spontaneous intracerebral hemorrhage (ICH) leaves most survivors dependent at follow-up. The importance of promoting M2-like microglial responses is increasingly recognized as a key element to ameliorate brain injury following ICH. The osmotherapeutic agents, mannitol and hypertonic saline (HTS), which are routinely used to reduce intracranial pressure, have been shown to reduce neuroinflammation in experimental ischemic and traumatic brain injury, but anti-inflammatory effects of osmotherapies have not been investigated in ICH. METHODS We studied the effects of iso-osmotic mannitol and HTS in rat models of ICH utilizing high-dose and moderate-dose collagenase injections into the basal ganglia, associated with high and low mortality, respectively. We studied the effects of osmotherapies, first given 5 h after ICH induction, and then administered every 12 h thereafter (4 doses total). Immunohistochemistry was used to quantify microglial activation and polarization. RESULTS Compared to controls, mannitol and HTS increased plasma osmolarity 1 h after infusion (301 ± 1.5, 315 ± 4.2 and 310 ± 2.0 mOsm/kg, respectively), reduced mortality at 48 h (82, 36 and 53%, respectively), and reduced hemispheric swelling at 48 h (32, 21, and 17%, respectively). In both perihematomal and contralateral tissues, mannitol and HTS reduced activation of microglia/macrophages (abundance and morphology of Iba1 + cells), and in perihematomal tissues, they reduced markers of the microglia/macrophage M1-like phenotype (nuclear p65, TNF, and NOS2), increased markers of the microglia/macrophage M2-like phenotype (arginase, YM1, and pSTAT3), and reduced infiltration of CD45 + cells. CONCLUSIONS Repeated dosing of osmotherapeutics at regular intervals may be a useful adjunct to reduce neuroinflammation following ICH.
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Affiliation(s)
- David L Schreibman
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Caron M Hong
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Kaspar Keledjian
- Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA
| | - Svetlana Ivanova
- Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA
| | - Solomiya Tsymbalyuk
- Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA
| | - Volodymyr Gerzanich
- Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA
| | - J Marc Simard
- Department of Neurosurgery, University of Maryland School of Medicine, 22 S. Greene St., Suite S12D, Baltimore, MD, 21201-1595, USA. .,Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. .,Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
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15
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Predicting cerebral edema in ischemic stroke patients. Neurol Sci 2019; 40:745-752. [PMID: 30659418 DOI: 10.1007/s10072-019-3717-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 01/10/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To produce a scoring system for predicting the development of edema in ischemic stroke patients without edema on admission. METHODS This retrospective study included 572 ischemic stroke patients (73.3 ± 13.0 years, 300 male) without signs of cerebral edema on the first CT scan, which was performed on admission. Another scan was normally performed 3 days later, and subsequently whenever needed. Edema was defined as cerebral hypodensity with compression of lateral ventricles. The main clinical, laboratory, and instrumental variables obtained during the first 24 h were related to the appearance of edema on the CT scans performed after the first one. RESULTS Cerebral edema occurred in 158 patients (27.6%) after a median time of 4 days. The variables independently associated with edema development were (odds ratio, 95% CI) the following: (1) total anterior circulation syndrome (4.20, 2.55-6.93; P < 0.0001), (2) hyperdense appearance of middle cerebral artery (4.12, 2.03-8.36; P = 0.0001), (3) closed eyes (2.53, 1.39-4.60; P = 0.002), (4) vomiting (3.53, 1.45-8.60; P = 0.006), (5) lacunar cerebral syndrome (0.36, 0.17-0.77; P = 0.008); and (6) white matter lesions (0.53, 0.33-0.86; P = 0.01). Counting one positive point for the first four variables and one negative point for the last two variables, a scoring system (E-score) was built. Cerebral edema could be predicted when the score was ≥ 1 (positive predictive value 61.6%, specificity 85.3%, sensitivity 62.0%). The area under the receiver operating characteristic curve was 0.78. CONCLUSIONS In ischemic stroke patients, six variables obtained during the first 24 h of hospitalization were predictive of subsequent cerebral edema development.
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16
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Wu S, Yuan R, Xiong Y, Zhang S, Wu B, Liu M. Clinical features, management and outcomes of severe ischaemic stroke in tertiary hospitals in China: protocol for a prospective multicentre registry-based observational study. BMJ Open 2018; 8:e024900. [PMID: 30373783 PMCID: PMC6224739 DOI: 10.1136/bmjopen-2018-024900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Severe ischaemic stroke is a devastating condition with high mortality and morbidity; however, there is insufficient evidence on its management. The aim of this study is to investigate causes, risk factors, clinical course, management and outcomes of severe ischaemic stroke in a real-world setting in tertiary hospitals in China. METHODS AND ANALYSIS This is a prospective, multicentre, registry-based observational study. We will recruit 2500 patients with acute ischaemic stroke from nine tertiary hospitals in Western China. Patients with acute ischaemic stroke admitted to the Department of Neurology within 30 days of stroke onset will be included. Patients will be visited within 24 hours after admission, on day 3, day 7 and at discharge, to collect data on their clinical state, blood biomarkers and brain imaging. Severe stroke is defined as severe neurological deficits (National Institute of Health Stroke Scale (NIHSS) ≥15 or in coma) on admission or clinical worsening (NIHSS increased by ≥4 scores) during hospitalisation. Patients will be followed up by structured telephone interviews at 3 months and 1 year after stroke onset. In-hospital outcomes include symptomatic haemorrhagic transformation and brain oedema by day 7 of admission, and survival status (death or survival) by discharge; follow-up outcomes will include survival status and functional outcome (assessed by modified Rankin Scale) at 3 months and 1 year. The current study will improve our knowledge about the development of severe ischaemic stroke at acute phase and factors influencing its outcomes, which will eventually facilitate optimisation of individualised interventions for its prevention and treatment. ETHICS AND DISSEMINATION Ethics approval is obtained from The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2017(130)). We will present our findings at the national and international conferences and peer-reviewed journals in stroke and neurology. TRIAL REGISTRATION NUMBER NCT03222024; Pre-results.
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Affiliation(s)
- Simiao Wu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ruozhen Yuan
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Yao Xiong
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Department of Neurology, The Third People’s Hospital of Chengdu, Chengdu, China
| | - Shihong Zhang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Wu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Ming Liu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
- Centre of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China
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17
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Venturelli PM, Appleton JP, Anderson CS, Bath PM. Acute Treatment of Stroke (Except Thrombectomy). Curr Neurol Neurosci Rep 2018; 18:77. [PMID: 30229395 DOI: 10.1007/s11910-018-0883-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
PURPOSE OF REVIEW The management of patients with acute stroke has been revolutionized in recent years with the advent of new effective treatments. In this rapidly evolving field, we provide an update on the management of acute stroke excluding thrombectomy, looking to recent, ongoing, and future trials. RECENT FINDINGS Large definitive trials have provided insight into acute stroke care including broadening the therapeutic window for thrombolysis, alternatives to standard dose alteplase, the use of dual antiplatelet therapy early after minor ischemic stroke, and treating elevated blood pressure in intracerebral hemorrhage. Further ongoing and future trials are eagerly awaited in this ever-expanding area. Although definitive trials have led to improvements in acute stroke care, there remains a need for further research to improve our understanding of pathophysiological mechanisms underlying different stroke types with the potential for treatments to be tailored to the individual.
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Affiliation(s)
- Paula Muñoz Venturelli
- Clinical Research Center, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.,Department of Neurology and Psychiatry, Clínica Alemana de Santiago, Santiago, Chile.,The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | - Jason P Appleton
- Stroke Trials Unit, Division of Clinical Neurosciences, University of Nottingham, Nottingham, UK.,Stroke, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Craig S Anderson
- Clinical Research Center, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile. .,The George Institute for Global Health, University of New South Wales, Sydney, Australia. .,The George Institute China at Peking University Health Science Center, Beijing, China.
| | - Philip M Bath
- Stroke Trials Unit, Division of Clinical Neurosciences, University of Nottingham, Nottingham, UK.,Stroke, Nottingham University Hospitals NHS Trust, Nottingham, UK
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18
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Wall ECB, Ajdukiewicz KMB, Bergman H, Heyderman RS, Garner P, Cochrane Acute Respiratory Infections Group. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev 2018; 2:CD008806. [PMID: 29405037 PMCID: PMC5815491 DOI: 10.1002/14651858.cd008806.pub3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Every day children and adults die from acute community-acquired bacterial meningitis, particularly in low-income countries, and survivors risk deafness, epilepsy and neurological disabilities. Osmotic therapies may attract extra-vascular fluid and reduce cerebral oedema, and thus reduce death and improve neurological outcomes.This is an update of a Cochrane Review first published in 2013. OBJECTIVES To evaluate the effects of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults on mortality, deafness and neurological disability. SEARCH METHODS We searched CENTRAL (2017, Issue 1), MEDLINE (1950 to 17 February 2017), Embase (1974 to 17 February 2017), CINAHL (1981 to 17 February 2017), LILACS (1982 to 17 February 2017) and registers of ongoing clinical trials (ClinicalTrials.com, WHO ICTRP) (21 February 2017). We also searched conference abstracts and contacted researchers in the field (up to 12 December 2015). SELECTION CRITERIA Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. DATA COLLECTION AND ANALYSIS Two review authors independently screened the search results and selected trials for inclusion. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS We included five trials with 1451 participants. Four trials evaluated glycerol against placebo, and one evaluated glycerol against 50% dextrose; in addition three trials evaluated dexamethasone and one trial evaluated acetaminophen (paracetamol) in a factorial design. Stratified analysis shows no effect modification with steroids; we present aggregate effect estimates.Compared to placebo, glycerol probably has little or no effect on death in people with bacterial meningitis (RR 1.08, 95% CI 0.90 to 1.30; 5 studies, 1272 participants; moderate-certainty evidence), but may reduce neurological disability (RR 0.73, 95% CI 0.53 to 1.00; 5 studies, 1270 participants; low-certainty evidence).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30; 4 studies, 1090 participants; low-certainty evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.64, 95% CI 0.44 to 0.93; 5 studies, 922 participants; low to moderate-certainty evidence).Glycerol probably has little or no effect on gastrointestinal bleeding (RR 0.93, 95% CI 0.39 to 2.19; 3 studies, 607 participants; moderate-certainty evidence). The evidence on nausea, vomiting and diarrhoea is uncertain (RR 1.09, 95% CI 0.81 to 1.47; 2 studies, 851 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS Glycerol was the only osmotic therapy evaluated, and data from trials to date have not demonstrated an effect on death. Glycerol may reduce neurological deficiency and deafness.
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Affiliation(s)
- Emma CB Wall
- University College LondonDivision of Infection and ImmunityGower StreetLondonUKWC1E 6BT
| | - Katherine MB Ajdukiewicz
- Pennine Acute Hospitals NHS TrustDepartment of Infectious DiseasesNorth Manchester General HospitalDelaunays Road, CrumpsallManchesterUKMB 5RB
| | - Hanna Bergman
- CochraneCochrane ResponseSt Albans House57‐59 HaymarketLondonUKSW1Y 4QX
| | - Robert S Heyderman
- University of Malawi College of MedicineMalawi‐Liverpool‐Wellcome Clinical Research ProgrammeP. O Box 30096BlantyreChichiriMalawi
| | - Paul Garner
- Liverpool School of Tropical MedicineDepartment of Clinical SciencesPembroke PlaceLiverpoolMerseysideUKL3 5QA
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19
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. OBJECTIVES To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS In May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Two review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data. MAIN RESULTS We identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events (SAEs): there was no significant difference in the total number of SAEs with cerebrolysin (RR 1.16, 95% CI 0.81 to 1.67). This comprised no difference in fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38) and an increase in the number of people with non-fatal SAEs (20/667 with cerebrolysin and 8/668 with placebo: RR 2.47, 95% CI 1.09 to 5.58, P = 0.03) (3 trials, 1335 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS The findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence of an increase in non-fatal SAEs with cerebrolysin use but not in total SAEs.
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Affiliation(s)
- Liliya Eugenevna Ziganshina
- Kazan (Volga region) Federal UniversityResearch & Education Centre for Evidence‐Based Medicine Cochrane Russia18 Kremlevskaya Street, 42000814‐15 Malaya Krasnaya Street, 420015KazanRussian Federation
| | - Tatyana Abakumova
- Kazan (Volga region) Federal UniversityDepartment of Basic and Clinical Pharmacology18 Kremlevskaya StreetKazanRussian Federation420008
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. OBJECTIVES To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS In May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases. We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma). SELECTION CRITERIA Randomised controlled trials (RCTs) comparing cerebrolysin, started within 48 hours of stroke onset and continued for any time, with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Two review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data. MAIN RESULTS We identified six RCTs (1501 participants) that met the inclusion criteria.We evaluated risk of bias and judged it to be unclear for generation of allocation sequence in four studies and low in two studies; unclear for allocation concealment in five studies and low in one study; high for incomplete outcome data (attrition bias) in five studies and unclear in one study; unclear for blinding; high for selective reporting in four studies and unclear in two; and high for other sources of bias in three studies and unclear in the rest. The manufacturer of cerebrolysin, pharmaceutical company EVER Neuro Pharma, supported three multi-centre studies, either totally, or providing cerebrolysin and placebo, randomisation codes, research grants, or statisticians.None of the included trials reported on poor functional outcome defined as death or dependence at the end of the follow-up period or early death (within two weeks of stroke onset).All-cause death: we extracted data from five trials (1417 participants). There was no difference in the number of deaths: 46/714 in cerebrolysin group versus 47/703 in placebo group; risk ratio (RR) 0.91 95% confidence interval (CI) 0.61 to 1.35 (5 trials, 1417 participants, moderate-quality evidence).Serious adverse events: two trials reported on this outcome, with 90% confidence cerebrolysin increased the risks of serious adverse events by at least one third compared to placebo: 62/589 in cerebrolysin group versus 46/600 in placebo group; RR 1.37 90% CI 1.01 to 1.86 (2 trials, 1189 participants, moderate-quality evidence).Total number of people with adverse events: three trials reported on this. There was no difference in the total number of people with adverse events: 308/667 in cerebrolysin group versus 307/668 in placebo group; RR 0.97 95% CI 0.86 to 1.09, random-effects model (3 trials, 1335 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS The findings of this Cochrane Review do not demonstrate clinical benefits of cerebrolysin for treating acute ischaemic stroke. We found moderate-quality evidence suggesting that serious adverse events may be more common with cerebrolysin use in acute ischaemic stroke.
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Affiliation(s)
- Liliya Eugenevna Ziganshina
- Kazan (Volga region) Federal UniversityDepartment of Basic and Clinical Pharmacology18 Kremlevskaya Street, 42000814‐15 Malaya Krasnaya Street, 420015KazanRussian Federation
| | - Tatyana Abakumova
- Kazan (Volga region) Federal UniversityDepartment of Basic and Clinical Pharmacology18 Kremlevskaya Street, 42000814‐15 Malaya Krasnaya Street, 420015KazanRussian Federation
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Mittal MK, LacKamp A. Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies. Front Neurol 2016; 7:210. [PMID: 27917153 PMCID: PMC5116572 DOI: 10.3389/fneur.2016.00210] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 11/08/2016] [Indexed: 12/30/2022] Open
Abstract
Intracerebral hemorrhage (ICH) is a medical emergency, which often leads to severe disability and death. ICH-related poor outcomes are due to primary injury causing structural damage and mass effect and secondary injury in the perihemorrhagic region over several days to weeks. Secondary injury after ICH can be due to hematoma expansion (HE) or a consequence of repair pathway along the continuum of neuroinflammation, neuronal death, and perihemorrhagic edema (PHE). This review article is focused on PHE and HE and will cover the animal studies, related human studies, and clinical trials relating to these mechanisms of secondary brain injury in ICH patients.
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Affiliation(s)
- Manoj K Mittal
- Department of Neurology, University of Kansas Medical Center , Kansas City, KS , USA
| | - Aaron LacKamp
- Department of Anesthesiology, University of Kansas Medical Center , Kansas City, KS , USA
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Hankey GJ. Glyburide for cerebral oedema: could an old dog have a new trick? Lancet Neurol 2016; 15:1109-11. [PMID: 27567242 DOI: 10.1016/s1474-4422(16)30198-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2016] [Accepted: 08/03/2016] [Indexed: 11/19/2022]
Affiliation(s)
- Graeme J Hankey
- School of Medicine and Pharmacology, University of Western Australia, Perkins Institute of Medical Research, QEII Medical Centre, Perth 6009, WA, Australia; Department of Neurology, Sir Charles Gairdner Hospital, Perth, WA, Australia; Western Australian Neuroscience Research Institute, Perth, WA, Australia.
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, China, and other Asian and post-Soviet countries. OBJECTIVES To assess the benefits and risks of Cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (October 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (November 2014), MEDLINE (1966 to November 2014), EMBASE (1974 to November 2014), Web of Science Core Collection, with Science Citation Index (1940 to November 2014), LILACS (1982 to December 2014), OpenGrey (1980 to December 2014), and a number of Russian Databases (1998 to December 2014). We also searched reference lists, ongoing trials registers and conference proceedings, and contacted the manufacturer of Cerebrolysin, EVER Neuro Pharma GmbH (formerly Ebewe Pharma). SELECTION CRITERIA Randomised controlled trials comparing Cerebrolysin started within 48 hours of stroke onset and continued for at least two weeks with placebo or no treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Two review authors independently applied inclusion criteria, assessed trial quality and risk of bias, and extracted data. MAIN RESULTS We included one trial involving 146 participants. We evaluated risk of bias and judged it to be high for generation of allocation sequence, low for allocation concealment, high for incomplete outcome data (attrition bias), unclear for blinding, high for selective reporting and high for other sources of bias. The manufacturer of Cerebrolysin, pharmaceutical company Ebewe, provided Cerebrolysin and the placebo, as well as the randomisation codes. There was no difference in the number of deaths (6/78 in Cerebrolysin group versus 6/68 in placebo group; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.29 to 2.58) or in the total number of adverse events (16.4% versus 10.3%; RR 1.62, 95% CI 0.69 to 3.82) between the treatment and control groups. AUTHORS' CONCLUSIONS Routine administration of Cerebrolysin to people with acute ischaemic stroke cannot be supported by the available evidence from RCTs.
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Affiliation(s)
- Liliya Eugenevna Ziganshina
- Department of Basic and Clinical Pharmacology, Kazan (Volga region) Federal University, 18 Kremlevskaya Street, 420008, 14-15 Malaya Krasnaya Street, 420015, Kazan, Tatarstan, Russian Federation
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Brogan ME, Manno EM. Treatment of malignant brain edema and increased intracranial pressure after stroke. Curr Treat Options Neurol 2014; 17:327. [PMID: 25398467 DOI: 10.1007/s11940-014-0327-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OPINION STATEMENT The management of patients with large territory ischemic strokes and the subsequent development of malignant brain edema and increased intracranial pressure is a significant challenge in modern neurology and neurocritical care. These patients are at high risk of subsequent neurologic decline and are best cared for in an intensive care unit or a comprehensive stroke center with access to neurosurgical support. Risks include hemorrhagic conversion, herniation, poor functional outcome, and death. This review discusses recent advances in understanding the pathophysiology of edema formation, identifying patients at risk, current management strategies, and emerging therapies.
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Affiliation(s)
- Michael E Brogan
- Neurological Intensive Care Unit, Cerebrovascular Center, Cleveland Clinic, 9500 Euclid Ave H/22, Cleveland, OH, 44139, USA
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Chen S, Zeng L, Hu Z. Progressing haemorrhagic stroke: categories, causes, mechanisms and managements. J Neurol 2014; 261:2061-78. [PMID: 24595959 PMCID: PMC4221651 DOI: 10.1007/s00415-014-7291-1] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Revised: 02/14/2014] [Accepted: 02/17/2014] [Indexed: 01/19/2023]
Abstract
Haemorrhagic stroke is a severe stroke subtype with high rates of morbidity and mortality. Although this condition has been recognised for a long time, the progressing haemorrhagic stroke has not received adequate attention, and it accounts for an even worse clinical outcome than the nonprogressing types of haemorrhagic stroke. In this review article, we categorised the progressing haemorrhagic stroke into acute progressing haemorrhagic stroke, subacute haemorrhagic stroke, and chronic progressing haemorrhagic stroke. Haematoma expansion, intraventricular haemorrhage, perihaematomal oedema, and inflammation, can all cause an acute progression of haemorrhagic stroke. Specific 'second peak' of perihaematomal oedema after intracerebral haemorrhage and 'tension haematoma' are the primary causes of subacute progression. For the chronic progressing haemorrhagic stroke, the occult vascular malformations, trauma, or radiologic brain surgeries can all cause a slowly expanding encapsulated haematoma. The mechanisms to each type of progressing haemorrhagic stroke is different, and the management of these three subtypes differs according to their causes and mechanisms. Conservative treatments are primarily considered in the acute progressing haemorrhagic stroke, whereas surgery is considered in the remaining two types.
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Affiliation(s)
- Shiyu Chen
- Department of Neurology, Xiangya Second Hospital, Central South University, 139 Renmin Road, Changsha, 410011 Hunan People’s Republic of China
| | - Liuwang Zeng
- Department of Neurology, Xiangya Second Hospital, Central South University, 139 Renmin Road, Changsha, 410011 Hunan People’s Republic of China
| | - Zhiping Hu
- Department of Neurology, Xiangya Second Hospital, Central South University, 139 Renmin Road, Changsha, 410011 Hunan People’s Republic of China
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Wall ECB, Ajdukiewicz KMB, Heyderman RS, Garner P. Osmotic therapies added to antibiotics for acute bacterial meningitis. Cochrane Database Syst Rev 2013; 3:CD008806. [PMID: 23543568 PMCID: PMC3996551 DOI: 10.1002/14651858.cd008806.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Every day children and adults throughout the world die from acute community-acquired bacterial meningitis, particularly in low-income countries. Survivors are at risk of deafness, epilepsy and neurological disabilities. Osmotic therapies have been proposed as an adjunct to improve mortality and morbidity from bacterial meningitis. The theory is that they will attract extra-vascular fluid by osmosis and thus reduce cerebral oedema by moving excess water from the brain into the blood. The intention is to thus reduce death and improve neurological outcomes. OBJECTIVES To evaluate the effects on mortality, deafness and neurological disability of osmotic therapies added to antibiotics for acute bacterial meningitis in children and adults. SEARCH METHODS We searched CENTRAL 2012, Issue 11, MEDLINE (1950 to November week 3, 2012), EMBASE (1974 to November 2012), CINAHL (1981 to November 2012), LILACS (1982 to November 2012) and registers of ongoing clinical trials (April 2012). We also searched conference abstracts and contacted researchers in the field. SELECTION CRITERIA Randomised controlled trials testing any osmotic therapy in adults or children with acute bacterial meningitis. DATA COLLECTION AND ANALYSIS Two review authors independently screened the search results and selected trials for inclusion. We collected data from each study for mortality, deafness, seizures and neurological disabilities. Results are presented using risk ratios (RR) and 95% confidence intervals (CI) and grouped according to whether the participants received steroids or not. MAIN RESULTS Four trials were included comprising 1091 participants. All compared glycerol (a water-soluble sugar alcohol) with a control; in three trials this was a placebo, and in one a small amount of 50% dextrose. Three trials included comparators of dexamethasone alone or in combination with glycerol. As dexamethasone appeared to have no modifying effect, we aggregated results across arms where both treatment and control groups received corticosteroids and where both treatment and control groups did not.Compared to placebo, glycerol may have little or no effect on death in people with bacterial meningitis (RR 1.09, 95% confidence interval (CI) 0.89 to 1.33, 1091 participants, four trials, low-quality evidence); or on death and neurological disability combined (RR 1.04, 95% CI 0.86 to 1.25).Glycerol may have little or no effect on seizures during treatment for meningitis (RR 1.08, 95% CI 0.90 to 1.30, 909 participants, three trials, low-quality evidence).Glycerol may reduce the risk of subsequent deafness (RR 0.60, 95% CI 0.38 to 0.93, 741 participants, four trials, low-quality evidence). AUTHORS' CONCLUSIONS The only osmotic diuretic to have undergone randomised evaluation is glycerol. Data from trials to date have not demonstrated benefit on death, but it may reduce deafness. Osmotic diuretics, including glycerol, should not be given to adults and children with bacterial meningitis unless as part of carefully conducted randomised controlled trial.
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Affiliation(s)
- Emma C B Wall
- International Health Group, Liverpool School of Tropical Medicine, Liverpool, UK.
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Wang DZ, Nair DS, Talkad AV. Acute Decompressive Hemicraniectomy to Control High Intracranial Pressure in Patients with Malignant MCA Ischemic Strokes. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2011; 13:225-32. [PMID: 21360089 DOI: 10.1007/s11936-011-0121-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
OPINION STATEMENT Malignant middle cerebral artery (MCA) infarction occurs in about 10% of all patients with supratentorial ischemic strokes. The infarction involves the entire MCA territory. Due to the consequences of severe brain edema, brain herniation, elevated intracranial pressure (ICP), and midline shift, these events carry a mortality rate of up to 80%. No clinical trials have been conducted to study the efficacy of the osmotic agents such as mannitol or hypertonic saline. Furthermore, aggressive use of such treatments may be detrimental. Surgical decompression has previously been proposed as a way to relieve the vicious cycle of malignant cerebral edema and reduced cerebral perfusion. Its use in relieving ICP is also controversial. Recently, a pooled analysis of three independent European trials has shown that decompressive hemicraniectomy is clearly beneficial in reducing mortality from large hemispheric infarctions. Although controversies still exist on its indications, surgical decompression can effectively reduce ICP, reduce mortality, and improve neurologic outcomes in selected patients with a malignant MCA stroke syndrome.
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Affiliation(s)
- David Z Wang
- INI Stroke Network, OSF Healthcare System, Department of Neurology, University of Illinois College of Medicine At Peoria, 530 NE Glen Oak Avenue, Peoria, IL, 61637, USA,
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Lopez GA, Afshinnik A, Samuels O. Care of the stroke patient: routine management to lifesaving treatment options. Neurotherapeutics 2011; 8:414-24. [PMID: 21748527 PMCID: PMC3250266 DOI: 10.1007/s13311-011-0061-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
The management of the acute ischemic stroke patient spans the time course from the emergency evaluation and treatment period through to the eventual discharge planning phase of stroke care. In this article we evaluate the literature and describe what have become standard treatments in the care of the stroke patient. We will review the literature that supports the use of a dedicated stroke unit for routine stroke care which has demonstrated reduced rates of morbidity and mortality. Also reviewed is the use of glycemic control in the initial setting along with data supporting the use of prophylactic treatments options in order to aide in the prevention of life threatening medical complications. In addition, lifesaving treatments will be discussed in light of new literature demonstrating reduced mortality in large hemispheric stroke patients undergoing surgical decompressive surgery. Both medical and surgical treatment options are discussed and compared.
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Affiliation(s)
- George A Lopez
- Department of Neurology, Houston Health Science Center, University of Texas, Houston, TX 77030, USA.
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Diringer MN, Scalfani MT, Zazulia AR, Videen TO, Dhar R. Cerebral hemodynamic and metabolic effects of equi-osmolar doses mannitol and 23.4% saline in patients with edema following large ischemic stroke. Neurocrit Care 2011; 14:11-7. [PMID: 21042881 DOI: 10.1007/s12028-010-9465-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Cerebral edema after ischemic stroke is frequently treated with mannitol and hypertonic saline (HS); however, their relative cerebrovascular and metabolic effects are incompletely understood, and may operate independent of their ability to lower intracranial pressure. METHODS We compared the effects of 20% mannitol and 23.4% saline on cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and oxygen metabolism (CMRO(2)), in nine ischemic stroke patients who deteriorated and had >2 mm midline shift on imaging. (15)O-PET was performed before and 1 h after administration of randomly assigned equi-osmolar doses of mannitol (1.0 g/kg) or 23.4% saline (0.686 mL/kg). RESULTS Baseline CBF values (ml/100g/min) in the infarct core, periinfarct region, remaining ipsilateral hemisphere, and contralateral hemisphere in the mannitol group were 5.0 ± 3.9, 25.6 ± 4.4, 35.6 ± 8.6, and 45.5 ± 2.2, respectively, and in the HS group were 8.3 ± 9.8, 35.3 ± 10.9, 38.2 ± 15.1, and 35.2 ± 12.4, respectively. There was a trend for CBF to rise in the contralateral hemisphere after mannitol from 45.5 ± 12.2 to 57.6 ± 21.7, P = 0.098, but not HS. CBV, OEF, and CMRO(2) did not change after administration of either agent. Change in CBF in the contralateral hemisphere after osmotic therapy was strongly correlated with baseline blood pressure (R (2)= 0.879, P = 0.002). CONCLUSIONS We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue. We conclude that at higher perfusion pressures, osmotic agents may raise CBF in non-ischemic tissue.
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Affiliation(s)
- Michael N Diringer
- Departments of Neurology and Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
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Okoromah CAN, Afolabi BB, Wall ECB, Cochrane Infectious Diseases Group. Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria. Cochrane Database Syst Rev 2011; 2011:CD004615. [PMID: 21491391 PMCID: PMC4018680 DOI: 10.1002/14651858.cd004615.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Cerebral oedema occurs with cerebral malaria, and some clinicians think osmotic diuretics, such as mannitol or urea, may improve outcomes. OBJECTIVES To compare mannitol or urea to placebo or no diuretic for treating children or adults with cerebral malaria. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (Issue 4, 2010), CENTRAL (The Cochrane Library Issue 12, 2010), MEDLINE (1966 to November 2010), EMBASE (1974 to November 2010), LILACS (1982 to November 2010), and the reference lists of articles. We contacted relevant organizations and researchers. SELECTION CRITERIA Randomized or quasi-randomized controlled trials comparing mannitol or urea to placebo or no treatment in children and adults with cerebral malaria. Primary outcomes were death, life-threatenining sequelae and major neurological sequelae at six months. DATA COLLECTION AND ANALYSIS Two authors applied the inclusion criteria, assessed risk of bias, and extracted data independently. MAIN RESULTS One trial met the inclusion criteria, comparing mannitol 20% to saline placebo in 156 Ugandan children. Allocation was concealed. No difference in mortality, time to regain consciousness, or neurological sequelae were detected. AUTHORS' CONCLUSIONS There are insufficient data to know what the effects of osmotic diuretics are in children with cerebral malaria. Larger, multicentre trials are needed.
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Affiliation(s)
- Christy AN Okoromah
- College of Medicine, University of LagosDepartment of Paediatrics and Child HealthIdi‐ArabaSurulereLagosLagosNigeriaPMB 12003
| | - Bosede B Afolabi
- University of LagosDepartment of Obstetrics and GynaecologyCollege of MedicinePMB 12003, Idi‐ArabaLagosNigeria
| | - Emma CB Wall
- Liverpool School of Tropical MedicineInternational Health GroupPembroke PlaceLiverpoolUKL3 5QA
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Abstract
BACKGROUND Intracerebral haemorrhage (ICH) causes significant morbidity and mortality. Prognosis for ICH patients is poor. Edaravone may be safe and effective in reducing the risk of early death and improving long-term functional outcomes in survivors. OBJECTIVES To assess the safety and efficacy of edaravone for acute ICH. SEARCH STRATEGY We searched the Cochrane Stroke Group Trials Register (March 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2 2010), the Chinese Stroke Trials Register (August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to March 2010) and 12 Chinese databases (August 2010). We also searched ongoing trials registers, reference lists, relevant conference proceedings and contacted companies manufacturing edaravone. SELECTION CRITERIA Randomised controlled trials (RCTs) in which edaravone was compared with placebo, or edaravone plus routine treatment was compared with routine treatment alone, in patients with acute ICH. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data, collected adverse events data and contacted trialists for missing information. MAIN RESULTS We included 10 RCTs involving 768 participants; quality was generally poor. For all trials, the control group was usual care/routine therapy (not placebo), treatment allocation and outcome evaluations were not blinded or not described, and the primary outcome (death or dependency at the end of long-term follow-up) was not reported. Only one trial reported deaths, indicating that edaravone treatment did not decrease the number of deaths significantly either during the scheduled treatment (RR 0.62, 95% CI 0.11 to 3.50) or at three month follow-up (RR 0.93, 95% CI 0.20 to 4.32). Four studies assessed activities of daily living (ADL) but ADL score was not improved significantly (MD 21.65, 95% CI -6.98 to 50.28) at the end of long-term follow-up. Combining data from all studies, edaravone treatment did increase the rate of improvement of neurological impairment (RR 1.48, 95% CI 1.29 to 1.69) until the end of the scheduled treatment, but it is not clear that this translates to any longer-term benefit of clinical importance. Reported adverse events with edaravone were mild and were common (9%), but there was no significant difference in adverse effect between the two groups (RR 2.09, 95% CI 0.71 to 6.19). AUTHORS' CONCLUSIONS All 10 studies were inconclusive in finding a beneficial or deleterious effect provided by edaravone for the treatment of ICH. Further high quality, large scale RCTs are required.
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Affiliation(s)
- Jie Yang
- (a) Department of Neurology, West China Hospital, Sichuan University, Chengdu, China, (b) Department of Neurology, Nanjing First Hospital, Nanjing, Jiangsu, China
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Wei JW, Huang Y, Wang JG, Liu M, Wong LKS, Huang Q, Wu L, Heeley EL, Arima H, Anderson CS. Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study. BMC Neurol 2011; 11:16. [PMID: 21276264 PMCID: PMC3040709 DOI: 10.1186/1471-2377-11-16] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2010] [Accepted: 01/30/2011] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND We aimed to examine current practice of the management and secondary prevention of intracerebral haemorrhage (ICH) in China where the disease is more common than in Western populations. METHODS Data on baseline characteristics, management in-hospital and post-stroke, and outcome of ICH patients are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) study, a multi-centre, prospective, 62 hospital registry in China during 2006-07. RESULTS Nearly all ICH patients (n = 1572) received an intravenous haemodiluting agent such as mannitol (96%) or a neuroprotectant (72%), and there was high use of intravenous traditional Chinese medicine (TCM) (42%). Neurosurgery was undertaken in 137 (9%) patients; being overweight, having a low Glasgow Coma Scale (GCS) score on admission, and Total Anterior Circulation Syndrome (TACS) clinical pattern on admission, were the only baseline factors associated with this intervention in multivariate analyses. Neurosurgery was associated with nearly three times higher risk of death/disability at 3 months post-stroke (odd ratio [OR] 2.60, p < 0.001). Continuation of antihypertensives in-hospital and at 3 and 12 months post-stroke was reported in 732/935 (78%), 775/935 (83%), and 752/935 (80%) living patients with hypertension, respectively. CONCLUSIONS The management of ICH in China is characterised by high rates of use of intravenous haemodiluting agents, neuroprotectants, and TCM, and of antihypertensives for secondary prevention. The controversial efficacy of these therapies, coupled with the current lack of treatments of proven benefit, is a call for action for more outcomes based research in ICH.
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Affiliation(s)
- Jade W Wei
- The George Institute for Global Health, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
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Kraft P, Benz PM, Austinat M, Brede ME, Schuh K, Walter U, Stoll G, Kleinschnitz C. Deficiency of vasodilator-stimulated phosphoprotein (VASP) increases blood-brain-barrier damage and edema formation after ischemic stroke in mice. PLoS One 2010; 5:e15106. [PMID: 21151938 PMCID: PMC2997079 DOI: 10.1371/journal.pone.0015106] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2010] [Accepted: 10/21/2010] [Indexed: 12/14/2022] Open
Abstract
Background Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP) is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification. Methodology/Principal Findings Focal cerebral ischemia was induced in Vasp−/− mice and wild-type (WT) littermates by transient middle cerebral artery occlusion (tMCAO). Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB) damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p<0.05) and edema volumes (1.7 mm3±0.5 mm3 versus 0.8 mm3±0.4 mm3; p<0.0001) were significantly enhanced in Vasp−/− mice compared to controls on day 1 after tMCAO. This was accompanied by a significant increase in infarct size (56.1 mm3±17.3 mm3 versus 39.3 mm3±10.7 mm3, respectively; p<0.01) and a non significant trend (p>0.05) towards worse neurological outcomes. Conclusion Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.
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Affiliation(s)
- Peter Kraft
- Department of Neurology, University of Würzburg, Würzburg, Germany
| | - Peter Michael Benz
- Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
- Department of Physiology, University of Würzburg, Würzburg, Germany
| | | | - Marc Elmar Brede
- Department of Anesthesiology, University of Würzburg, Würzburg, Germany
| | - Kai Schuh
- Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
- Department of Physiology, University of Würzburg, Würzburg, Germany
| | - Ulrich Walter
- Institute for Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
| | - Guido Stoll
- Department of Neurology, University of Würzburg, Würzburg, Germany
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Josephson CB, Frantzias J, Samarasekera N, Al-Shahi Salman R. The persisting burden of intracerebral haemorrhage: can effective treatments be found? PLoS Med 2010; 7:e1000353. [PMID: 20976102 PMCID: PMC2957399 DOI: 10.1371/journal.pmed.1000353] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Colin Josephson, Rustam Al-Shahi Salman, and colleagues discuss the effectiveness of treatments for intracerebral haemorrhage.
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Affiliation(s)
- Colin B. Josephson
- Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
| | - Joseph Frantzias
- Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
| | - Neshika Samarasekera
- Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
| | - Rustam Al-Shahi Salman
- Division of Clinical Neurosciences, Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
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Abstract
BACKGROUND Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue which has proposed neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia and China. OBJECTIVES To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke. SEARCH STRATEGY We searched the Cochrane Stroke Group Trials Register (February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to February 2009), EMBASE (1974 to February 2009), LILACS (1982 to February 2009), Science Citation Index (1940 to February 2009), SIGLE Archive (1980 to March 2005), and a number of relevant Russian Databases (1988 to February 2009). We also searched reference lists, ongoing trials registers and conference proceedings. SELECTION CRITERIA Randomised controlled trials comparing cerebrolysin with placebo or no treatment in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS Three review authors independently applied the inclusion criteria, assessed trial quality and extracted the data. MAIN RESULTS We included one trial involving 146 participants. There was no difference in death (6/78 in the cerebrolysin group versus 6/68 in the placebo group; risk ratio (RR) 0.87, 95% confidence interval (CI) 0.29 to 2.58) or in the total number of adverse events (16.4% versus 10.3%; RR 1.62, 95% CI 0.69 to 3.82) between the treatment and control groups. AUTHORS' CONCLUSIONS There is not enough evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischaemic stroke. High-quality and large-scale randomised controlled trials may help to gain a better understanding of the potential value of cerebrolysin in acute ischaemic stroke.
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Affiliation(s)
- Lilia E Ziganshina
- Department of Clinical Pharmacology and Pharmacotherapy, Kazan State Medical Academy, 11 Mushtari Street, 420012, 14-15 Malaya Krasnaya Street, 420015, Kazan, Tatarstan, Russian Federation
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Abstract
Cerebrovascular disease is defined as any abnormality of the brain resulting from a pathologic process affecting its blood supply. Stroke or cerebrovascular accident (CVA) is the most common clinical manifestation of cerebrovascular disease, and can be broadly divided into ischemic stroke and hemorrhagic stroke. Ischemic stroke results from occlusion of a cerebral blood vessel by a thrombus or embolism, depriving the brain of oxygen and glucose, whereas hemorrhagic stroke results from rupture of a blood vessel wall within the brain parenchyma or subarachnoid space. Previously considered uncommon, CVA is being recognized with greater frequency in veterinary medicine since magnetic resonance imaging has become more readily available. Once the diagnosis of ischemic or hemorrhagic stroke is confirmed, potential underlying causes should be sought after and treated accordingly.
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Abstract
BACKGROUND Because spontaneous (non-traumatic) intracerebral haemorrhage (ICH) volume influences its outcome and a third of ICHs enlarge by a third within 24 hours of onset, early haemostatic drug therapy might improve outcome. This is an update of a Cochrane review first published in 2006. OBJECTIVES To examine the clinical effectiveness and safety of haemostatic drug therapies for acute ICH in a randomised controlled trial (RCT) design. SEARCH STRATEGY I searched the Cochrane Stroke Group Trials Register (last searched 26 June 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In an effort to identify further published, ongoing and unpublished studies I scanned bibliographies of relevant articles, searched international registers of clinical trials and research, and contacted authors and pharmaceutical companies. SELECTION CRITERIA I sought RCTs of any haemostatic drug therapy for acute ICH, compared against placebo or open control, with relevant clinical outcome measures. DATA COLLECTION AND ANALYSIS Two authors independently applied the inclusion criteria, reviewed the relevant studies, and extracted data. MAIN RESULTS I found five phase II RCTs and one phase III RCT, involving 1398 adults aged 18 years or over, within four hours of ICH onset: 423 participants received placebo and 975 participants received haemostatic drugs (two received epsilon-aminocaproic acid (EACA) and 973 received recombinant activated factor VII (rFVIIa)). Haemostatic drugs did not significantly reduce 90-day case fatality after ICH (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.58 to 1.25), and rFVIIa did not significantly reduce death or dependence on the modified Rankin Scale (grades 4 to 6) within 90 days of ICH (RR 0.91, 95% CI 0.72 to 1.15). There was a trend towards more participants on rFVIIa experiencing thromboembolic serious adverse events (RR 1.37, 95% CI 0.74 to 2.55) AUTHORS' CONCLUSIONS Haemostatic drugs cannot be recommended for the treatment of acute spontaneous ICH in clinical practice, but a large RCT would be justified.
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Affiliation(s)
- Rustam Al-Shahi Salman
- Division of Clinical Neurosciences, University of Edinburgh, Bramwell Dott Building, Western General Hospital, Edinburgh, Midlothian, UK, EH4 2XU
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Affiliation(s)
- Dániel Bereczki
- From the Department of Neurology (D.B.), Semmelweis University, Budapest, Hungary; the Department of Neurology (D.B., I.F.), Health Science and Medical Center, University of Debrecen, Hungary; the Department of Neurology (M.L.), West China Hospital, Sichuan University, China; and the Department of Internal Medicine (G.F.d.P.), Federal University of Sao Paulo, Brazil
| | - Ming Liu
- From the Department of Neurology (D.B.), Semmelweis University, Budapest, Hungary; the Department of Neurology (D.B., I.F.), Health Science and Medical Center, University of Debrecen, Hungary; the Department of Neurology (M.L.), West China Hospital, Sichuan University, China; and the Department of Internal Medicine (G.F.d.P.), Federal University of Sao Paulo, Brazil
| | - Gilmar Fernandes do Prado
- From the Department of Neurology (D.B.), Semmelweis University, Budapest, Hungary; the Department of Neurology (D.B., I.F.), Health Science and Medical Center, University of Debrecen, Hungary; the Department of Neurology (M.L.), West China Hospital, Sichuan University, China; and the Department of Internal Medicine (G.F.d.P.), Federal University of Sao Paulo, Brazil
| | - István Fekete
- From the Department of Neurology (D.B.), Semmelweis University, Budapest, Hungary; the Department of Neurology (D.B., I.F.), Health Science and Medical Center, University of Debrecen, Hungary; the Department of Neurology (M.L.), West China Hospital, Sichuan University, China; and the Department of Internal Medicine (G.F.d.P.), Federal University of Sao Paulo, Brazil
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Tan G, Zhou J, Yuan D, Sun S. Formula for use of mannitol in patients with intracerebral haemorrhage and high intracranial pressure. Clin Drug Investig 2008; 28:81-7. [PMID: 18211116 DOI: 10.2165/00044011-200828020-00002] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND AND OBJECTIVE Although mannitol has been widely used in hospitals to treat patients with high intracranial pressure (ICP) secondary to intracerebral haemorrhage (ICH), no universal agreement has been reached regarding the optimal dosage of this agent for achieving appropriate intracranial decompression. The aim of this study was to investigate the effects of different mannitol dosages on ICP and the effects of other factors, such as sex, age, haemorrhage location and haematoma volume, on the ICP-lowering effect of mannitol. The data obtained were then used to construct a formula for estimating the total dosage of mannitol required to reduce ICP in individual patients with ICH. PATIENTS AND METHODS A total of 72 patients with ICH and elevated ICP monitored in our intensive care unit were included in this study. Patients with ICH who had hypoxaemia (arterial oxygen saturation <90%), severe functional disturbances of the liver or kidney, acidosis or pathological changes in the visual conducting pathway were not included in this study. Each patient received 20% intravenous mannitol 125 mL every 4, 6 or 8 hours per day to treat elevated ICP, with ICP levels being measured before administration of mannitol and at least three times per day during administration of the drug. When the ICP reached a fixed level, the dosage of mannitol was gradually reduced. The total dosage of mannitol used to reduce the ICP from the highest value to the fixed value was calculated. Data on the patients' sex, age, haemorrhage location and haematoma volume were also obtained. Multivariate regression analysis of the results enabled development of a formula for use of mannitol in patients with ICH and elevated ICP. RESULTS Use of mannitol significantly decreased ICP in all patients. The effect of mannitol on ICP reduction was dose-dependent during the period of ICP reduction (p < 0.05) but not after the ICP had reached a fixed level; this limited effectiveness of mannitol when its dosage reaches a certain level was termed 'mannitol saturation dosage'. The reduction in ICP with mannitol was not statistically significantly affected by the patient's sex or age, but was significantly correlated with both haemorrhage location and haematoma volume (p < 0.05). The reduction in ICP with mannitol was greater in patients with supratentorial ICH compared with those with infratentorial ICH (p < 0.0001). CONCLUSION The total mannitol dosage required for individual patients with ICH and elevated ICP can be calculated by considering the location of the haemorrhage, the volume of the haematoma and the pretreated ICP reading. To this end, the following formula was derived in the study: Total dosage of mannitol (mL of 20% mannitol) = (x + 31.17900 x y - 3.39853 x z - 244.47590)/0.00752, where x = the pretreated ICP (mmH(2)O), y = the haemorrhage location (supratentorial ICH: y = 0, infratentorial ICH: y = 1) and z = the volume of haematoma (mL). Use of this formula in the clinical setting should help reduce the possibility of adverse effects resulting from administration of excessive dosages of mannitol.
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Affiliation(s)
- Ge Tan
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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