Circadian Rhythm and Risk of Hemorrhagic Transformation after Acute Ischemic Stroke Treated with Intravenous Thrombolysis - A Systematic Review.

BACKGROUND: A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent. OBJECTIVES: This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence. METHODS: We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis. RESULTS: From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality. CONCLUSION: ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.

The Burden of Cerebral Venous Thrombosis in a Romanian Population across a 5-Year Period.

Health policies in transitioning health systems are rarely informed by the social burden and the incidence shifts in disease epidemiology. Cerebral venous thrombosis (CVT) is a type of stroke more often affecting younger adults and women, with higher incidences being reported in recent studies. A retrospective, hospital-based population study was conducted at Cluj-Napoca Emergency County Hospital across a 5-year period between 2017 and 2021. The overall incidence and the rates in distinctive gender and age groups were assessed. Length of hospital stay (LHS), modified Rankin score (mRS) and mortality at discharge and at 3 months were calculated. Fifty-three patients were included. The median age was 45 years, and 64.2% were women. In our population of 3,043,998 person-years, 53 CVT cases resulted in an incidence of 1.74 per 100,000 (95% CI 1.30-2.27). CVT incidence was higher in women (2.13 per 100,000, 95% CI 1.47-2.07). There was a statistically significant difference in LHS between patients with different intracranial complications (Kruskal-Wallis, p = 0.008). The discharge mRS correlated with increasing age (rs = 0.334, p = 0.015), transient risk factors (Fisher's exact test, p = 0.023) and intracranial complications (Fisher's exact test, p = 0.022). In addition, the mRS at 3 months was statistically associated with increasing age (rs = 0.372, p = 0.006) and transient risk factors (Fisher's exact test, p = 0.012). In-hospital mortality was 5.7%, and mortality at follow up was 7.5%, with higher rates in women (5.9% and 8.8%, respectively). Our findings may provide insight regarding the epidemiological features of certain patient groups more prone to developing CVT and its complications, informing local and central stakeholders' efforts to improve standards of care.

A retrospective, multi-center cohort study evaluating the severity- related effects of cerebrolysin treatment on clinical outcomes in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of death and disability for which there is currently no effective drug therapy available. Because drugs targeting a single TBI pathological pathway have failed to show clinical efficacy to date, pleiotropic agents with effects on multiple mechanisms of secondary brain damage could represent an effective option to improve brain recovery and clinical outcome in TBI patients. In this multicenter retrospective study, we investigated severity-related efficacy and safety of the add-on therapy with two concentrations (20 ml/day or 30 ml/day) of Cerebrolysin (EVER Neuro Pharma, Austria) in TBI patients. Adjunctive treatment with Cerrebrolysin started within 48 hours after TBI and clinical outcomes were ranked according to the Glasgow Outcome Scale and the Modified Rankin Disability Score at 10 and 30 days post-TBI. Analyses of efficacy were performed separately for subgroups of patients with mild, moderate or severe TBI according to Glasgow Coma Scale scores at admission. Compared to standard medical care alone (control group), both doses of Cerebrolysin were associated with improved clinical outcome scores at 10 days post-TBI in mild patients and at 10 and 30 days in moderate and severe cases. A dose-dependent effect of Cerebrolysin on TBI recovery was supported by the dose-related differences and the significant correlations with treatment duration observed for outcome measures. The safety and tolerability of Cerebrolysin in TBI patients was very good. In conclusion, the results of this large retrospective study revealed that early Cerebrolysin treatment is safe and is associated to improved TBI outcome.

Cranioplasty with custom-made implants: analyzing the cases of 10 patients.

PURPOSE: The aim of this study was to assess quantitatively whether a symmetric reconstruction of the calvaria could be achieved using 3-dimensional (3D) custom-made implants and to examine any complications caused by the cranioplasty. PATIENTS AND METHODS: Custom-made cranial implants were produced using data obtained from computed tomographic scanning of the defect using computer-aided design and rapid prototyping techniques. Polymethylmethacrylate was used as the reconstruction material and the implant was cast from a silicone rubber mold. These implants were used in 10 patients (9 men and 1 woman) who previously received a craniectomy. The symmetry gained after cranioplasty was quantified by volumetric analysis using 3D reconstructed postoperative computed tomographic imaging. Any complications after cranioplasty also were recorded. RESULTS: The average follow-up was 42.5 months (range, 7 to 85 mo). The esthetic appearance of all patients was much improved. When the volume of the reconstructed right calvaria was compared with the left calvaria, the difference was not statistically significant (P > .05). There were 2 cases of complications. One exhibited a transient seroma collection. Another had a wrinkle formation in the forehead. No infectious episodes or signs of plate rejection were encountered. CONCLUSIONS: The custom-made implants for cranioplasty showed a significant improvement in morphology. The implants may be very useful for repairing large and complex-shaped cranial defects. The technique may be useful for the bone reconstruction of other sites.

Primary pituitary abscess followed by empty sella syndrome in an adolescent girl.

Primary pituitary abscess is a rare pituitary pathology, particularly at a young age and is characterized by atypical clinical features making the diagnosis difficult. Correct diagnosis and therapy are mandatory due to the potentially lethal outcome of pituitary infection. We report the case of an adolescent girl presenting with headache, diabetes insipidus and central thyro-gonadic insufficiency with no history of infection, in whom the intra-operative diagnosis of primary pituitary abscess was made. Bacterial cultures indicated infection with Streptococcus spp. One year after neurosurgery and antibiotic therapy, recovery of diabetes insipidus and pituitary insufficiency was documented except for persistence of subnormal growth hormone secretion. Post-surgery, pituitary magnetic resonance imaging revealed an empty sella syndrome.

Silicone rubber mould cast polyethylmethacrylate-hydroxyapatite plate used for repairing a large skull defect.

INTRODUCTION: Reconstruction of the cranial vault is performed for various reasons and precise repair of the defect is important. A modified method of cranioplasty is presented using three-dimensional (3D) models and polyethylmethacrylate mixed with hydroxyapatite, cast in a silicone rubber mould. PATIENT AND METHOD: A large custom made cranial implant was produced using data acquired from 3D computer tomography, rapid prototyping and cast in a silicone rubber mould. This plate was then applied to a 53 year-old man who had undergone a decompressive fronto-parieto-temporo-occipital craniotomy. The bone flap had been lost due to infection. The cranioplasty was performed at 1 year after the initial operation. RESULTS: The cranial plate fitted precisely into the defect and needed no correction at the time of surgery. The stability of the reconstruction plate was increased by the presence of thin margins allowed by silicone rubber elasticity. No complications occurred and the final functional and aesthetic results were good. CONCLUSION: The use of 3D imaging and rapid prototyping allow precise repair of large skull defects, with good aesthetic and functional results. At the same time, silicone rubber moulds permit the production of very thin details needed not only for cosmetic reasons but for reconstruction plate stability as well.