Spontaneous Heterotopic Pregnancy with Unaffected Intrauterine Pregnancy: Systematic Review of Clinical Outcomes.

Background and objective: Spontaneous heterotopic pregnancy (SHP) is a rare condition represented by the synchronous coexistence of an intrauterine and an ectopic pregnancy. It rarely occurs with natural conception and is usually a consequence of assisted reproductive techniques. Diagnosis of SHP can be a challenge for the clinician. The evolution of the intrauterine pregnancy is dependent on many factors, such as the location of the heterotopic pregnancy, gestational age at the time of diagnosis, the surgical procedure, the presence of other risk factors, early or delayed management. The aim of this systematic review of the literature was to extract existing evidence on spontaneous heterotopic pregnancy with otherwise unaffected intrauterine pregnancy. Materials and Methods: From a total of 1907 database entries identified in PubMed, EMBASE and Cochrane reviews, we selected 18 papers for narrative synthesis, for which we explored the diagnostic options, treatment, and outcome of these extremely rare epidemiologic occurrences. Manuscripts were assessed using the CARE guidelines for reporting case reports. Results: The main symptom was abdominal pain, and the preferred treatment approach was surgical, more precisely, using a laparoscopic approach. Most cases presented no risk factors, and the diagnosis was mostly made in the first semester. Conclusions: Normal follow-up and evolution of intrauterine pregnancy have been observed regardless of surgical approach (open or laparoscopic). Early diagnosis and treatment are advised, as they impact maternal and fetal outcomes. Evidence on this topic is scarce, predominantly comprised of case reports with variable degrees of adherence to dissemination guidelines. More studies on this topic are required to optimize care protocols for this type of pregnancy.

Non-Invasive Systems Application in Traumatic Brain Injury Rehabilitation.

Traumatic brain injury (TBI) is a significant public health concern, often leading to long-lasting impairments in cognitive, motor and sensory functions. The rapid development of non-invasive systems has revolutionized the field of TBI rehabilitation by offering modern and effective interventions. This narrative review explores the application of non-invasive technologies, including electroencephalography (EEG), quantitative electroencephalography (qEEG), brain-computer interface (BCI), eye tracking, near-infrared spectroscopy (NIRS), functional near-infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) in assessing TBI consequences, and repetitive transcranial magnetic stimulation (rTMS), low-level laser therapy (LLLT), neurofeedback, transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS) and virtual reality (VR) as therapeutic approaches for TBI rehabilitation. In pursuit of advancing TBI rehabilitation, this narrative review highlights the promising potential of non-invasive technologies. We emphasize the need for future research and clinical trials to elucidate their mechanisms of action, refine treatment protocols, and ensure their widespread adoption in TBI rehabilitation settings.

Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury: a three-arm randomized trial.

Introduction: Traumatic brain injury (TBI) is a major public health problem affecting millions worldwide. Despite significant advances in medical care, there are limited effective interventions for improving cognitive and functional outcomes in TBI patients. Methods: This randomized controlled trial investigated the safety and efficacy of combining repetitive transcranial magnetic stimulation (rTMS) and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. Ninety-three patients with TBI were randomized to receive either Cerebrolysin and rTMS (CRB + rTMS), Cerebrolysin and sham stimulation (CRB + SHM), or placebo and sham stimulation (PLC + SHM). The primary outcome measures were the composite cognitive outcome scores at 3 and 6 months after TBI. Safety and tolerability were also assessed. Results: The study results demonstrated that the combined intervention of rTMS and Cerebrolysin was safe and well-tolerated by patients with TBI. Although no statistically significant differences were observed in the primary outcome measures, the descriptive trends in the study support existing literature on the efficacy and safety of rTMS and Cerebrolysin. Discussion: The findings of this study suggest that rTMS and Cerebrolysin may be effective interventions for improving cognitive and functional outcomes in TBI patients. However, limitations of the study, such as the small sample size and exclusion of specific patient populations, should be considered when interpreting the results. This study provides preliminary evidence for the safety and potential efficacy of combining rTMS and Cerebrolysin in improving cognitive and functional outcomes in TBI patients. The study highlights the importance of multidisciplinary approaches in TBI rehabilitation and the potential for combining neuropsychological measurements and interventions to optimize patient outcomes. Conclusion: Further research is needed to establish these findings' generalizability and identify the optimal dosages and treatment protocols for rTMS and Cerebrolysin.

Quantitative EEG as a Biomarker in Evaluating Post-Stroke Depression.

Introduction: Post-stroke depression (PSD) has complex pathophysiology determined by various biological and psychological factors. Although it is a long-term complication of stroke, PSD is often underdiagnosed. Given the diagnostic role of quantitative electroencephalography (qEEG) in depression, it was investigated whether a possible marker of PSD could be identified by observing the evolution of the (Delta + Theta)/(Alpha + Beta) Ratio (DTABR), respectively the Delta/Alpha Ratio (DAR) values in post-stroke depressed patients (evaluated through the HADS-D subscale). Methods: The current paper analyzed the data of 57 patients initially selected from a randomized control trial (RCT) that assessed the role of N-Pep 12 in stroke rehabilitation. EEG recordings from the original trial database were analyzed using signal processing techniques, respecting the conditions (eyes open, eyes closed), and several cognitive tasks. Results: We observed two significant associations between the DTABR values and the HADS-D scores of post-stroke depressed patients for each of the two visits (V1 and V2) of the N-Pep 12 trial. We recorded the relationships in the Global (V1 = 30 to 120 days after stroke) and Frontal Extended (V2 = 90 days after stroke) regions during cognitive tasks that trained attention and working memory. For the second visit, the association between the analyzed variables was negative. Conclusions: As both our relationships were described during the cognitive condition, we can state that the neural networks involved in processing attention and working memory might go through a reorganization process one to four months after the stroke onset. After a period longer than six months, the process could localize itself at the level of frontal regions, highlighting a possible divergence between the local frontal dynamics and the subjective well-being of stroke survivors. QEEG parameters linked to stroke progression evolution (like DAR or DTABR) can facilitate the identification of the most common neuropsychiatric complication in stroke survivors.

Role and Impact of Cerebrolysin for Ischemic Stroke Care.

Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of neuroprotection and neurorecovery have been vigorously investigated in a substantial number of clinical studies in the past, only a few trials managed to increase the number of promising outcomes with regard to the multidimensional construct of brain protection and rehabilitation. In terms of pharmacological therapies with proven benefits in the post-ischemic process, drugs with neurorestorative properties are thought to be effective in both the acute and chronic phases of stroke. One significant example is Cerebrolysin, a combination of amino acids and peptides that mimic the biological functions of neurotrophic factors, which has been shown to improve outcomes after ischemic stroke, while preserving a promising safety profile. The purpose of this paper is to offer an overview on the role and impact of Cerebrolysin for ischemic stroke care, by touching on various aspects, from its complex, multimodal and pleiotropic mechanism of action, to its efficacy and safety, as well as cost effectiveness.

The economic burden of stroke: a systematic review of cost of illness studies.

Stroke is one of the leading causes of morbidity and mortality worldwide. As the number of stroke cases is rising from one year to another, policymakers require data on the amount spent on stroke to enforce better financing policies for prevention, hospital care, outpatient rehabilitation services and social services. We aimed to systematically assess the economic burden of stroke at global level. Cost of stroke studies were retrieved from five databases. We retrieved the average cost per patient, where specified, or estimated it using a top-down approach. Resulting costs were grouped in two main categories: per patient per year and per patient lifetime. We extracted information from forty-six cost of illness studies. Per patient per year costs are larger in high income countries and in studies conducted from the payer perspective. The highest average per patient per year cost by country was reported in the United States ($59,900), followed by Sweden ($52,725) and Spain ($41,950). The highest per patient lifetime costs were reported in Australia ($232,100) for all identified definitions of stroke. Existing literature regarding the economic burden of stroke is concentrated in high-income settings, with very few studies conducted in South America and Africa. Published manuscripts on this topic highlight substantial methodological heterogeneity, rendering comparisons difficult or impossible, even within the same country or among studies with similar costing perspectives.

The Effect of Cerebrolysin on the Predictive Value of Baseline Prognostic Risk Score in Moderate and Severe Traumatic Brain Injury.

Cognitive dysfunction is a significant complaint among patients after moderate to severe traumatic brain injury (TBI), with devastating consequences on functional recovery and quality of life. Prognostic models allow a better assessment and management of neurotrauma patients. The aim of the study was to demonstrate the predictive value of the Baseline Prognostic Risk Score (BPRS) in moderate to severe TBI, in a sample of patients treated with neurotrophic factors. Eighty patients with moderate-severe TBI from the CAPTAIN II study were included in secondary data analysis. Patients received active treatment with Cerebrolysin, 50 mL per day for ten days, followed by two treatment cycles with 10 mL per day for ten days. BPRS was determined on admission; the age was recorded, and patients were evaluated using the following neurocognitive tests: Mini-Mental State Essay (MMSE), Wechsler Adult Intelligence Scale-Third Edition Processing Speed Index (WAIS-III PSI) and Stroop Colour Word Test-Victoria Version at 10, 30 and 90 days. Hierarchical regression analysis was performed to investigate the unique predictive value of BPRS on cognitive evolution, independent of age. BPRS independently predicted scores on the WAIS-III PSI DSCales and the Word subscale of the Stroop Colour Word Test at 90 days. Age was a significant predictor for all the investigated scales at 10, 30, and 90 days. This study demonstrates the predictive value of a validated prognostic model (BPRS) for medium-term neurocognitive outcomes in a sample of moderate-severe traumatic brain injury treated with neurotrophic factors.

Prediction of Neurocognitive Outcome after Moderate-Severe Traumatic Brain Injury Using Serum Neuron-Specific Enolase and S100 biomarkers.

Seric biomarkers have been tested in a large number of studies on traumatic brain injuries (TBI) patients in order to predict severity, especially related to the short-term outcome. However, TBI patients have a high risk of developing long-term complications such as physical disability, cognitive impairment, psychiatric pathology, epilepsy, and others. The aim of this study was to assess the correlation between protein biomarkers S100 and neuron-specific enolase (NSE) and neurocognitive status at 10- and 90-days post-injury. Both biomarkers were tested in the first 4h and after 72h post-injury in 62 patients with moderate-severe TBI. The patients were evaluated by a series of neurocognitive tests: Early Rehabilitation Barthel Index (ERBI), Glasgow Outcome Scale-Extended (GOSE), The Mini-Mental State Examination (MMSE), Processing Speed Index (PSI), and Stroop Test, at 10 and 90 days post-injury and supplementary by the Hospital Anxiety and Depression Scale at 90 days. For evaluating the whole neurocognitive status instead of every scale separately, we used Structural Equation Modeling (SEM), while for anxiety and depressive symptoms, we used multiple regression analyses. SEM showed that NSE values at 4 hours were significant predictors of the cognitive status at 10 (p=0.034) and 90 days (p= 0.023). Also, there were found significant correlations between NSE at 4h and the anxiety level. This study demonstrated a significant correlation between NSE at 4h and short and medium-term neuropsychological outcomes, which recommends using this biomarker for selecting patients with a higher risk of cognitive dysfunction.