Primjena ultrazvuka pri izboru bolesnika s ishemijskim moždanim udarom za trombolitičku terapiju

Transcranial Doppler (TCD) in acute ischemic stroke can be used as a convenient screening test to identify the level of arterial occlusion and presence of residual flow, and to monitor recanalization. It can help to minimize the number of invasive angiograms and facilitate fast diagnostic work-up of stroke patients. Clinical recovery in tissue plasminogen activator (TPA) treated patients is associated with early complete recanalization. Dramatic clinical recovery during TPA infusion was seen in 20% of patients when TPA was combined with continuous TCD monitoring of the occlusion site. Ultrasonic energy transmission by TCD monitoring may expose more clot surface to residual blood flow and thus facilitate thrombolysis.U bolesnika s akutnim ishemijskim moždanim udarom transkranijski dopler (TCD) može se upotrijebiti kao prikladna metoda za identifikaciju stupnja arterijske okluzije, prisutnosti rezidualnog protoka kao i za monitoriranje rekanalizacije. TCD može pomoći u smanjivanju broja invazivnih angiografija i može olakšati brzu dijagnostičku obradu bolesnika s moždanim udarom. Klinički oporavak bolesnika koji su liječeni s tkivnim plazminogen aktivatorom (TPA) povezan je s ranom potpunom rekanalizacijom. Dramatični klinički oporavak za vrijeme infuzije TPA primijećen je u 20% bolesnika kada je TPA primijenjen istovremeno s kontinuiranim TCD monitoriranjem okludirane žile. Ultrazvučna energija koja se prenosi TCD monitoriranjem može izložiti veću površinu ugruška rezidualnom protoku krvi i na taj način olakšati trombolizu

Ultrazvukom pojačana tromboliza kod moždanog udara

Spontaneous arterial recanalization occurs at a rate of 6% per hour, and it can be doubled with intravenous tissue plasminogen activator (TPA) therapy since early dramatic clinical improvement, a substitute for early thrombus break-up, occurs in TPA treated patients. TPA activity can be enhanced with ultrasound including 2 MHz transcranial Doppler (TCD). TCD identifies residual blood flow signals around thrombi, and, by delivering mechanical pressure waves, exposes more thrombus surface to circulating TPA. In the CLOTBUST trial, the dramatic clinical recovery from stroke coupled with complete recanalization within 2 hours after TPA bolus occurred in 25% of patients treated with TPA+TCD compared to 8% of those that received TPA alone (p=0.02). Complete clearance of a thrombus and dramatic recovery of brain function during treatment are feasible goals for ultrasound-enhanced thrombolysis that can lead to sustained recovery. An early boost in brain perfusion seen in the CLOTBUST target group resulted in a trend of 13% more patients achieving favorable outcome at 3 months, thus providing the rationale for a pivotal trial. The ability of TPA to break up thrombi can be further enhanced with harmless diagnostic ultrasound contrast agents. Current ongoing clinical trials include phase II studies of 2 MHz TCD with ultrasound contrast agents, or microbubbles: TCD+TPA+Levovist; TCD+TPA+MRX nano-platform (C3F8 ImaRx). Intra-arterial ultrasound-enhanced TPA delivery is tested in the Interventional Management of Stroke (IMS) clinical trial using 1.7-2.1 MHz pulsed wave ultrasound catheter (EKOS). Dose escalation studies of microbubbles, ultrasound exposure and the development of an operator independent ultrasound device are currently underway.Spontana arterijska rekanalizacija odvija se po stopi od 6% na sat, što se može udvostručiti pomoću terapije intravenskim aktivatorom tkivnog plazminogena (TPA), jer u bolesnika liječenih pomoću TPA dolazi do ranog dramatičnog kliničkog poboljšanja kao nadomjestak za rano razbijanje tromba. Aktivnost TPA može se pojačati ultrazvukom uključujući transkranijski Doppler (TCD) od 2 MHz. TCD identificira signale ostatnog krvnog protoka oko trombusa te kroz stvaranje valova mehaničkog tlaka izlaže veću površinu tromba cirkulirajućem TPA. U pokusu CLOTBUST je značajan klinički oporavak od moždanog udara uz potpunu rekanalizaciju unutar 2 sata od davanja bolusa TPA nastupio u 25% bolesnika liječenih pomoću TPA+TCD, u usporedbi s 8% bolesnika koji su primili samo TPA (p=0,02). Potpuno uklanjanje tromba i značajan oporavak moždane funkcije tijekom liječenja izvedivi su ciljevi ultrazvukom pojačane trombolize koji mogu dovesti do održivog oporavka. Kao rezultat ranog stimuliranja moždane perfuzije, zabilježenog u ciljnoj skupini studije CLOTBUST, 13% više bolesnika postiglo je povoljan ishod nakon 3 mjeseca, pruživši time razlog za ključni pokus. Sposobnost TPA da razbije trombe može se dodatno pojačati neškodljivim dijagnostičkim kontrastnim sredstvima za ultrazvuk. Upravo su u tijeku kliničke studije 2. faze s kontrastnim sredstvima za ultrazvuk od 2 MHz ili mikrokuglicama TCD+TPA+Levovist; TCD+TPA+MRX nano-platforma (C3F8 ImaRx). Intraarterijsko davanje TPA pojačano ultrazvukom ispituje se u kliničkom pokusu Interventional Management of Stroke (IMS) uz primjenu ultrazvučnog katetera pulsnih valova od 1,7-2,1 MHz (EKOS). U tijeku su studije pojačavanja mikrokuglica, izlaganja ultrazvuku, kao i razvoj ultrazvučnog uređaja neovisnog o operatoru

Post Stroke Depression

Depression is the most common neuropsychiatric disorder affecting over one third of all stroke patients. The presence of depression after a stroke greatly affects the ability of patients to participate in rehabilitation and can even affect their long-term mortality. Poststroke depression is a well-documented and studied aspect of stroke management because of the implications it has on morbidity, mortality and recovery. Despite post stroke depression being a well-studied phenomenon, it remains underdiagnosed. The development of poststroke depression is multifactorial and has been evaluated from the cellular, genetic, and environmental perspective. Using numerous studies this chapter will review facets of post stroke depression such as epidemiology, etiology and treatment, while evaluating how this phenomena effects patient recovery and rehabilitation

Percutaneous transluminal angioplasty and stenting for symptomatic intracranial arterial stenosis: a systematic review and meta-analysis

OBJECTIVES: The cumulative safety and efficacy measures of percutaneous transluminal angioplasty and stenting (PTAS) for secondary stroke prevention in patients with symptomatic intracranial arterial stenosis (sICAS) have not previously been evaluated using a meta-analytical approach. METHODS: We conducted a systematic review and random effects meta-analysis of all available randomized controlled trials (RCTs) evaluating the safety and efficacy of PTAS (in comparison with medical therapy) for sICAS. RESULTS: Three RCTs (678 total patients) were included in the quantitative analysis. PTAS was associated with a higher risk of recurrent ischemic stroke in the territory of qualifying artery both within 30 days [risk ratio (RR) = 2.21, 95% confidence interval (CI) 1.10-4.43] and 1 year (RR = 1.92, 95% CI 1.10-3.36). PTAS was also related to a higher risk of any ischemic stroke within 30 days from the index event (RR = 2.08, 95% CI 1.17-3.71). The risk for intracranial hemorrhage was found to be higher in PTAS patients both within 30 days (RR = 10.60, 95% CI 1.98-56.62) and 1 year (RR = 8.15, 95% CI 1.50-44.34). The composite outcome of any stroke or death within 1 year (RR = 2.29, 95% CI 1.13-4.66) and 2 years (RR = 1.52, 95% CI 1.04-2.21) was higher in PTAS than in medical therapy. PTAS was associated with a higher risk of any stroke or death within 2 years in the sICAS subgroup located in posterior circulation (RR = 2.37, 95% CI 1.27-4.42). CONCLUSIONS: PTAS is associated with adverse early and long-term outcomes and should not be recommended in patients with sICAS. Further research to identify subgroups of patients who could also serve as candidates for future interventional trials along with efforts to reduce procedure-related complications are needed

Glavobolja i afazija u mlade žene s nedostatkom proteina S i nefrotskim sindromom

We present sequential brain imaging findings in a young woman who while being evaluated for a newly discovered nephrotic syndrome developed headache followed by aphasia. The patient’s symptoms were due to cerebral venous thrombosis in the setting of protein S deficiency and oral contraception.Predstavljamo sekvencijski nalaz slikovnog prikaza mozga mlade žene kod koje je tijekom kliničke evaluacije novootkrivenog nefrotskog sindroma došlo do pojave glavobolje praćene afazijom. Simptomi su bili uzrokovani cerebralnom venskom trombozom koja se razvila uslijed nedostatka proteina S i uporabe oralnih kontraceptiva

Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke

Sonotrombolisis; Endovascular; Cambio de equilibrio clínicoSonothrombolysis; Endovascular; Equipoise shiftSonotrombolisis; Endovascular; Canvi d'equilibri clínicBackground: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. Methods: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. Results: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06-0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89-1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0-2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01-2.31; p = 0.04). Conclusion: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies

On Pure Spinor Superfield Formalism

We show that a certain superfield formalism can be used to find an off-shell supersymmetric description for some supersymmetric field theories where conventional superfield formalism does not work. This "new" formalism contains even auxiliary variables in addition to conventional odd super-coordinates. The idea of this construction is similar to the pure spinor formalism developed by N.Berkovits. It is demonstrated that using this formalism it is possible to prove that the certain Chern-Simons-like (Witten's OSFT-like) theory can be considered as an off-shell version for some on-shell supersymmetric field theories. We use the simplest non-trivial model found in [2] to illustrate the power of this pure spinor superfield formalism. Then we redo all the calculations for the case of 10-dimensional Super-Yang-Mills theory. The construction of off-shell description for this theory is more subtle in comparison with the model of [2] and requires additional Z_2 projection. We discover experimentally (through a direct explicit calculation) a non-trivial Z_2 duality at the level of Feynman diagrams. The nature of this duality requires a better investigation