A narrative review of risk factors and predictors for poor outcome and prolonged recovery after a mild traumatic brain injury.

Mild traumatic brain injuries (mTBI) are often caused by a blow to the head or a sudden jolt resulting in a wide range of physical, cognitive, and emotional temporary symptoms. Mild TBI diagnosis can be challenging and most commonly followed by post-concussion syndrome (PCS). When the symptoms are present for more than 3 months, prolonged post-concussive syndrome (PPCS) can be suspected. This review aims to identify and summarize the current status of the knowledge regarding the risk factors and predictors of the recovery from PCS and PPCS. A comprehensive search of the main scientific databases (PubMed, Web of Science, Embase, and Cochrane Library) was performed using keywords, such as: 'prolonged post-concussion syndrome', combined with 'risk factors', 'predictors', and 'outcomes'. Multiple studies reported more than one risk factor for PPCS development following mTBIs that were generally the results of sports-related concussions and car accidents. The most prevalent risk factor associated with PPCS was the female sex. Social factors/personality traits, anxiety, mental health disorders, or other health conditions from their past medical history, the occurrence of headache/migraines during TBI recovery, somatization, physical activity, and litigation were also reported to contribute to PPCS risk. An exhaustive approach is required to mitigate the risk of PPCS and to ensure optimal recovery after concussive events. However, larger prospective cohort studies evaluating patients that were examined and treated with standardized protocols could be needed to further validate these associations and mandate the highest risk factors for delayed recovery.

Understanding Functional Neurological Disorder: Recent Insights and Diagnostic Challenges.

Functional neurological disorder (FND), formerly called conversion disorder, is a condition characterized by neurological symptoms that lack an identifiable organic purpose. These signs, which can consist of motor, sensory, or cognitive disturbances, are not deliberately produced and often vary in severity. Its diagnosis is predicated on clinical evaluation and the exclusion of other medical or psychiatric situations. Its treatment typically involves a multidisciplinary technique addressing each of the neurological symptoms and underlying psychological factors via a mixture of medical management, psychotherapy, and supportive interventions. Recent advances in neuroimaging and a deeper exploration of its epidemiology, pathophysiology, and clinical presentation have shed new light on this disorder. This paper synthesizes the current knowledge on FND, focusing on its epidemiology and underlying mechanisms, neuroimaging insights, and the differentiation of FND from feigning or malingering. This review highlights the phenotypic heterogeneity of FND and the diagnostic challenges it presents. It also discusses the significant role of neuroimaging in unraveling the complex neural underpinnings of FND and its potential in predicting treatment response. This paper underscores the importance of a nuanced understanding of FND in informing clinical practice and guiding future research. With advancements in neuroimaging techniques and growing recognition of the disorder's multifaceted nature, the paper suggests a promising trajectory toward more effective, personalized treatment strategies and a better overall understanding of the disorder.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

Neuropathological findings in essential tremor.

Essential tremor (ET) is one of the most common neurological conditions and the most common movement disorder. The pathophysiological mechanisms that underlie this entity have not yet been described. However, recent post-mortem brain studies have provided useful insight into the underlying pathology of ET. Two brain areas have been consistently found to present neuropathological alterations in patients with ET: the brainstem, for presence of Lewy bodies or neuronal depletion, and the cerebellum, regarding Purkinje cells' morphology and density. In the present study we aim to review the literature on the main neuropathological findings in ET brains.

A review of the personality traits in post-concussion syndrome.

INTRODUCTION: Various manifestations ranging from physical symptoms to cognitive and emotional impairments could often be seen following head concussions that lead to mild traumatic brain injury (mTBI). These symptoms are commonly comprising the post-concussion syndrome (PCS) and their resolution could be influenced by multiple factors. Personality traits have been suggested as potential risk factors for the emergence and persistence of PCS. In this study, we aimed to investigate the possible predisposition to PCS given by certain personality traits. METHODS: Prospective cohort studies, observational studies, and cross-phenotype polygenic risk score analyses were selected from the main scientific databases (PubMed/Medline, Scopus, EMBASE, Web of Science) based on multiple-step screening, using keywords (such as "personality traits", "post-concussion syndrome", "traumatic brain injury", "anxiety", "depression", "resilience", and "somatization") and inclusion/exclusion criteria (English written studies available in full text presenting relevant data on TBI patients and their personality traits; reviews, animal studies, and studies not written in English, not available in full text, or not presenting full demographical and clinical data were excluded). The investigated personality traits included emotional reserve, somatic trait anxiety, embitterment, mistrust, parental anxiety, state anxiety, trait anxiety, anxiety sensitivity, pain catastrophizing, helplessness, sports-concussion symptom load, and cognitive resilience. RESULTS: The reviewed data from 16 selected studies suggested that personality traits play an essential role in the development and persistence of PCS. Emotional reserve, cognitive resilience, and lower levels of somatic trait anxiety were associated with better outcomes in PCS. However, higher levels of anxiety sensitivity, pain catastrophizing, helplessness, and sports-concussion symptom load were associated with worse outcomes in PCS. Parental anxiety was not associated with persistent symptoms in children following concussion. Despite the statistical analysis regarding the included publications bias was low, further studies should further investigate the correlation between TBI and some personality traits, as some of the selected studies did not included healthy individuals and their psychological profiles for comparison and correlation analysis. CONCLUSION: Personality traits may help predict the development and persistence of PCS following mTBI. Understanding the personality traits roles in PCS could assist the development of targeted interventions for the prevention and treatment of PCS. Further research is needed to better understand the complex interactions between personality traits, neurobiological factors, and psychosocial factors in PCS.

Oxytocin Enhances Time-Dependent Responses in the Aggressive Zebrafish (Danio rerio).

Autism spectrum disorder (ASD) has become one of the most well-known disorders encountered since early childhood among people. Nowadays, the main concerns are its high prevalence and the lack of proper therapeutic interventions. In this way, the necessity of using animal models that can mimic some of the spectrum symptoms, besides deepening the mechanisms of occurrence, is undeniable. Oxytocin (OT) is often mentioned and linked to producing social domain improvements. The goal of the present study was to determine if different time exposures to OT can trigger distinct behavioral responses in zebrafish, potentially offering insights into autism therapy. To accomplish this goal, zebrafish were exposed to the same dose of OT (33.2 ng/mL OT) for one week but with different time frames, such as: continuous exposure for seven days, fifteen minutes per day for seven days, and every two days for the same amount of time. The behavior of the fish was recorded using the EthoVision XT 11.5 software, and each trial lasted four minutes. Specific parameters for locomotor activity and aggressive behavior were measured. Overall, zebrafish exposure to OT generated several improvements in locomotor activity and aggressive behavior. Moreover, the differences in the exposure period indicated that time is an important factor, showing that continuous exposure to OT was linked with better performance than exposure to the hormone every two days. At the same time, the most variable results were observed in the case of fish exposed every day to OT. Exposure to OT could lead to certain improvements in zebrafish behavior that can be time-sensitive. Nevertheless, further work is needed in order to investigate the mechanisms of action of OT in an ASD context.

A Systematic Review and Meta-Analysis of the Inflammatory Biomarkers in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite its high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI has been previously provided. Thus, this systematic review and meta-analysis aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. In this regard, eight studies comprising 1184 individuals were selected. Thus, it was shown that the increase in IL-6, TNF-α, and IL-1ß plasma levels could be implicated in the development of early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

Epidemiology, Risk Factors, and Biomarkers of Post-Traumatic Epilepsy: A Comprehensive Overview.

This paper presents an in-depth exploration of Post-Traumatic Epilepsy (PTE), a complex neurological disorder following traumatic brain injury (TBI), characterized by recurrent, unprovoked seizures. With TBI being a global health concern, understanding PTE is crucial for effective diagnosis, management, and prognosis. This study aims to provide a comprehensive overview of the epidemiology, risk factors, and emerging biomarkers of PTE, thereby informing clinical practice and guiding future research. The epidemiological aspect of the study reveals PTE as a significant contributor to acquired epilepsies, with varying incidence influenced by injury severity, age, and intracranial pathologies. The paper delves into the multifactorial nature of PTE risk factors, encompassing clinical, demographic, and genetic elements. Key insights include the association of injury severity, intracranial hemorrhages, and early seizures with increased PTE risk, and the roles of age, gender, and genetic predispositions. Advancements in neuroimaging, electroencephalography, and molecular biology are presented, highlighting their roles in identifying potential PTE biomarkers. These biomarkers, ranging from radiological signs to electroencephalography EEG patterns and molecular indicators, hold promise for enhancing PTE pathogenesis understanding, early diagnosis, and therapeutic guidance. The paper also discusses the critical roles of astrocytes and microglia in PTE, emphasizing the significance of neuroinflammation in PTE development. The insights from this review suggest potential therapeutic targets in neuroinflammation pathways. In conclusion, this paper synthesizes current knowledge in the field, emphasizing the need for continued research and a multidisciplinary approach to effectively manage PTE. Future research directions include longitudinal studies for a better understanding of TBI and PTE outcomes, and the development of targeted interventions based on individualized risk profiles. This research contributes significantly to the broader understanding of epilepsy and TBI.

Patients' and caregivers' attitudes towards patient assisted suicide or euthanasia in amyotrophic lateral sclerosis-a meta-analysis.

Assisted suicide and euthanasia are long debated topics in amyotrophic lateral sclerosis (ALS) patients care. We conducted a meta-analysis to evaluate the attitudes of ALS patients and their caregivers toward physician-assisted suicide (PAS) and euthanasia. Also, we were interested to identify the factors associated with the positive or negative attitude of patients and caregivers towards PAS/euthanasia. A thorough search of the online databases (PubMed, Cochrane Library, and Web of Science) was conducted and eligibility criteria according to the PRISMA guidelines were used to include the studies in the current meta-analysis. The assessment of the quality of the selected studies was carried out using a pre-specified set of criteria by Cochrane. The studies that were selected for this meta-analysis suggested that the expression of the wish to die is more likely correlated with depression, anxiety, hopelessness, and lack of optimism. The overall prevalence of considering PAS/euthanasia significantly varies in a dependent manner over the cultural, legal, and societal factors. In this context, we found that the opinion on this topic can be deeply personal and may vary widely among individuals and communities. Lower quality of life and lower religiosity were associated with a positive attitude toward PAS/euthanasia. On the other hand, patients who are more religious are less likely to choose PAS/euthanasia. Gender does not appear to play a significant role in determining attitudes towards PAS/euthanasia in ALS patients. Other factors, such as education and psychological state, could also be important. In conclusion, end-of-life decisions in ALS patients are complex and require careful consideration of individual values, beliefs, and preferences. Understanding the factors that influence a patient's attitude towards PAS/euthanasia can help healthcare providers to offer appropriate care and support for these patients and their families.

The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. Methods: We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. Results: The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Conclusions: Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

Exploring Symptom Overlaps: Post-COVID-19 Neurological Syndrome and Post-Concussion Syndrome in Athletes.

The COVID-19 pandemic has introduced new challenges in managing neurological conditions, particularly among athletes. This paper explores the intersection of post-COVID-19 neurological syndrome (PCNS/PASC) and post-concussion syndrome (PCS), focusing on their implications in sports medicine. Our analysis covers the symptomatology, pathophysiology, and management strategies for PCNS/PASC and PPCS, with special attention paid to the unique challenges faced by athletes recovering from these conditions, including the risk of symptom exacerbation and prolonged recovery. Key findings reveal that both PCNS/PASC and PPCS present with overlapping symptoms such as cognitive difficulties, exercise intolerance, and mental health issues, but differ in specific manifestations like anosmia and ageusia, unique to COVID-19. Pathophysiological analysis reveals similarities in blood-brain barrier disruption (BBB) but differences in the extent of immune activation. Management strategies emphasize a gradual increase in physical activity, close symptom monitoring, and psychological support, with a tailored approach for athletes. Specific interventions include progressive aerobic exercises, resistance training, and cognitive rehabilitation. Furthermore, our study highlights the importance of integrating neurology, psychiatry, physical therapy, and sports medicine to develop comprehensive care strategies. Our findings underscore the dual challenge of COVID-19 and concussion in athletes, necessitating a nuanced, interdisciplinary approach to effective management. Future research should focus on the long-term neurological effects of both conditions and optimizing treatment protocols to improve patient outcomes. This comprehensive understanding is crucial for advancing the management of athletes affected by these overlapping conditions and ensuring their safe return to sports.

Exploring the Potential of Exosomal Biomarkers in Mild Traumatic Brain Injury and Post-Concussion Syndrome: A Systematic Review.

BACKGROUND: Alongside their long-term effects, post-concussion syndrome (PCS) and mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. In this study, we aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. METHODS: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. RESULTS: The analyzed studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aß), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS as well as repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. CONCLUSION: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.

Mild Traumatic Brain Injury as a Risk Factor for Parkinsonism, Tics, and Akathisia: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was conducted using PubMed, Embase, and Cochrane Library databases. Studies were eligible if they reported on the association between MTBI and Parkinsonism. Pooled odds ratios (ORs) were calculated using a random-effects model. Publication bias was assessed using Egger's and Begg's tests. A total of 18 studies were included in this meta-analysis, with 1,484,752 participants. The overall OR for Parkinsonism in individuals with a history of mTBI was 1.637 (95% CI, 1.203-2.230; p = 0.01), indicating a significant association. The OR for Parkinson's disease (PD) specifically was 1.717 (95% CI, 1.206-2.447; p = 0.01). However, insufficient data on tics and akathisia limited a meta-analysis. There was no evidence of publication bias according to Egger's (p = 0.8107) and Begg's (p = 0.4717) tests. This meta-analysis provides evidence that mTBI is a significant risk factor for Parkinsonism, particularly PD. However, the findings should be interpreted with caution due to the heterogeneity among the studies included and the study's limitations. Further research is needed to confirm these findings and to investigate the underlying mechanisms of the mTBI-Parkinsonism association.