Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches.

Cognitive impairment in patients with Parkinson's disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut-brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.

Genetic Insights into the Molecular Pathophysiology of Depression in Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies. Materials and Methods: we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression. Results: in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene, SLC6A4, tryptophan hydrolase-2 gene, TPH2), dopamine metabolism and neurotransmission (dopamine receptor D3 gene, DRD3, aldehyde dehydrogenase 2 gene, ALDH2), neurotrophic factors (brain-derived neurotrophic factor gene, BDNF), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene, TEF), the sodium-dependent neutral amino acid transporter B(0)AT2 gene, SLC6A15), and PARK16 genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (SLC6A3), monoamine oxidase A (MAOA) and B (MAOB) genes, catechol-O-methyltransferase gene (COMT), CRY1, and CRY2 have not been related to PD depression. Conclusions: the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.

Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review.

Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind-body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.

Drug-Induced Liver Injury in Hospitalized Patients during SARS-CoV-2 Infection.

In the last few years, the world has had to face the SARS-CoV-2 infection and its multiple effects. Even though COVID-19 was first considered to be a respiratory disease, it has an extended clinical spectrum with symptoms occurring in many tissues, and it is now identified as a systematic disease. Therefore, various drugs are used during the therapy of hospitalized COVID-19 patients. Studies have shown that many of these drugs could have adverse side-effects, including drug-induced liver injury-also known as DILI-which is the focus of our review. Despite the consistent findings, the pathophysiological mechanism behind DILI in COVID-19 disease is still complex, and there are a few risk factors related to it. However, when it comes to the diagnosis, there are specific algorithms (including the RUCAM algorithm) and biomarkers that can assist in identifying DILI and which we will analyze in our review. As indicated by the title, a variety of drugs are associated with this COVID-19-related complication, including systemic corticosteroids, drugs used for the therapy of uncontrolled cytokine storm, as well as antiviral, anti-inflammatory, and anticoagulant drugs. Bearing in mind that hepatotoxicity is very likely to occur during COVID-19, especially in patients treated with multiple medications, we will also refer to the use of other drugs used for DILI therapy in an effort to control and prevent a severe and long-term outcome.

Cytomegalovirus pneumonia in an immunocompetent host with primary ciliary dyskinesia: A case report.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive inherited disease caused by mutations in genes involved in ciliary structure and function leading to impaired mucociliary clearance and repeated or chronic, usually bacterial, infections of the upper and lower airways and decreased lung function and bronchiectasis. Cytomegalovirus (CMV) is a DNA virus that usually causes subclinical infection and in 10% of the patients causes a mononucleosis-like syndrome. CMV is a causative agent of serious illness in vulnerable immunocompromised groups such as transplant recipients, patients with immunodeficiency or malignancy and neonates. Life-threatening infection due to CMV, including CMV pneumonia, is not common in immunocompetent patients. In this report we describe a case of an otherwise immunocompetent woman, suffering from PCD, who developed severe CMV pneumonia.

Pulmonary adverse events due to immune checkpoint inhibitors: A literature review.

Cancer immunotherapy aims to stimulate the immune system to fight against tumors, utilizing the presentation of molecules on the surface of the malignant cells that can be recognized by the antibodies of the immune system. Immune checkpoint inhibitors, a type of cancer immunotherapy, are broadly used in different types of cancer, improving patients' survival and quality of life. However, treatment with these agents causes immune-related toxicities affecting many organs. The most frequent pulmonary adverse event is pneumonitis representing a non-infective inflammation localized to the interstitium and alveoli. Other lung toxicities include airway disease, pulmonary vasculitis, sarcoid-like reactions, infections, pleural effusions, pulmonary nodules, diaphragm myositis and allergic bronchopulmonary aspergillosis. This review aims to summarize these pulmonary adverse events, underlining the significance of an optimal expeditious diagnosis and management.

The parallel lives of pandemics: COVID­19 and obesity.

The present article discusses the interconnectedness of coronavirus disease 2019 (COVID-19) and obesity as global health crises. The similarities between the two conditions are highlighted; these include shared risk factors and comorbidities, and the impact of obesity on the immune system. The present article also mentions the challenges faced in combating both pandemics, including misinformation and prejudice against obesity. It discusses the development of therapeutic medications and vaccines for COVID-19 and the potential of injectable incretin analogues for weight loss. Socioeconomic issues are also addressed, with obesity being more prevalent in lower socioeconomic groups and the cost of obesity treatments being a barrier for those in need. The present article emphasizes the need for comprehensive and sustainable solutions, including public health interventions, education, policy changes and equitable distribution of resources, to address both COVID-19 and obesity.

Malignant character of an ossified posterior longitudinal ligament in a hyperflexion injury: A case report.

The present study reports the case of a 50-year-old obese male with ankylosing spondylitis, Scheuermann's kyphosis. The patient was asymptomatic concerning the ectopic ossification of the posterior longitudinal ligament (OPLL) at the cervical spine; he developed quadriparesis and respiratory insufficiency following minor head trauma. Even though trauma to the cervical spine in patients with OPLL is common, to the best of our knowledge, this is the first reported case of an extensive osteophyte with a lethal outcome after syncope. In rare occasions, it may be present with syncope and potentially lethal outcomes, particularly when precipitated by trauma. Therefore, the management of OPLL with significant canal stenosis should not be unnecessarily delayed.

A mid­pandemic night's dream: Melatonin, from harbinger of anti­inflammation to mitochondrial savior in acute and long COVID­19 (Review).

Coronavirus disease 2019 (COVID­19), a systemic illness caused by severe acute respiratory distress syndrome 2 (SARS­CoV­2), has triggered a worldwide pandemic with symptoms ranging from asymptomatic to chronic, affecting practically every organ. Melatonin, an ancient antioxidant found in all living organisms, has been suggested as a safe and effective therapeutic option for the treatment of SARS­CoV­2 infection due to its good safety characteristics and broad­spectrum antiviral medication properties. Melatonin is essential in various metabolic pathways and governs physiological processes, such as the sleep­wake cycle and circadian rhythms. It exhibits oncostatic, anti­inflammatory, antioxidant and anti­aging properties, exhibiting promise for use in the treatment of numerous disorders, including COVID­19. The preventive and therapeutic effects of melatonin have been widely explored in a number of conditions and have been well­established in experimental ischemia/reperfusion investigations, particularly in coronary heart disease and stroke. Clinical research evaluating the use of melatonin in COVID­19 has shown various improved outcomes, including reduced hospitalization durations; however, the trials are small. Melatonin can alleviate mitochondrial dysfunction in COVID­19, improve immune cell function and provide antioxidant properties. However, its therapeutic potential remains underexplored due to funding limitations and thus further investigations are required.

Association between polymorphisms of DNA repair genes and intracranial aneurysms: A systematic review and meta­analysis.

Intracranial aneurysms (IAs) are present in ~2% of the general population, and genetic factors cannot be excluded for the risk of their development. The gene factors that result in the changes in the vascular extracellular matrix (ECM) may also be a key reason for IAs being hereditary. The VCAN gene [also known as chondroitin sulfate proteoglycan 2 (CSPG2)] plays various roles in maintaining ECM functions. The present systematic review and meta-analysis aimed to investigate all eligible articles involving IAs on the association with germ line SNPs of DNA repair genes (up to January, 2024). The total number of patients was 2,308 [987 cases (poor outcomes) and 1,321 controls (good outcomes)]. The results revealed that rs2287926 G/G genotype and G allele and rs251124 T/T genotype and minor allele T increased the risk of developing IAs. However, further studies are required to examine these gene polymorphisms as screening markers for IAs.

Exploring the association between melatonin and nicotine dependence (Review).

Due to the addictive qualities of tobacco products and the compulsive craving and dependence associated with their use, nicotine dependence continues to be a serious public health concern on a global scale. Despite awareness of the associated health risks, nicotine addiction contributes to numerous acute and chronic medical conditions, including cardiovascular disease, respiratory disorders and cancer. The nocturnal secretion of pineal melatonin, known as the 'hormone of darkness', influences circadian rhythms and is implicated in addiction­related behaviors. Melatonin receptors are found throughout the brain, influencing dopaminergic neurotransmission and potentially attenuating nicotine­seeking behavior. Additionally, the antioxidant properties of melatonin may mitigate oxidative stress from chronic nicotine exposure, reducing cellular damage and lowering the risk of nicotine­related health issues. In addition to its effects on circadian rhythmicity, melatonin acting via specific neural receptors influences sleep and mood, and provides neuroprotection. Disruptions in melatonin signaling may contribute to sleep disturbances and mood disorders, highlighting the potential therapeutic role of melatonin in addiction and psychiatric conditions. Melatonin may influence neurotransmitter systems involved in addiction, such as the dopaminergic, glutamatergic, serotonergic and endogenous opioid systems. Preclinical studies suggest the potential of melatonin in modulating reward processing, attenuating drug­induced hyperactivity and reducing opioid withdrawal symptoms. Chronotherapeutic approaches targeting circadian rhythms and melatonin signaling show promise in smoking cessation interventions. Melatonin supplementation during periods of heightened nicotine cravings may alleviate withdrawal symptoms and reduce the reinforcing effects of nicotine. Further research is required however, to examine the molecular mechanisms underlying the melatonin­nicotine association and the optimization of therapeutic interventions. Challenges include variability in individual responses to melatonin, optimal dosing regimens and identifying biomarkers of treatment response. Understanding these complexities could lead to personalized treatment strategies and improve smoking cessation outcomes.

Precision medicine for respiratory diseases: A current viewpoint.

In the realm of respiratory illnesses, despite the immense costs and efforts invested in diagnosis and treatment, numerous patients with chronic respiratory conditions or malignancies do not respond well to existing therapies. Delayed diagnoses and inadequate treatments contribute to these challenges, along with adverse reactions or treatment limitations due to side-effects. However, recent advancements in understanding respiratory diseases have paved the way for personalized medical treatments, considering individual genetic, molecular and environmental factors. Precision medicine, which accommodates individual differences in disease susceptibility and response to treatments, aims to improve patient care by aligning medical research with tailored therapies. Innovative technologies, such as genomic sequencing and biomarker identification contribute to this approach, allowing for customized treatments and the identification of effective therapies. Additionally, the application of precision medicine in lung cancer treatment exemplifies the forefront of individualized care within respiratory medicine. Several studies have explored the role of precision medicine in managing respiratory infectious diseases, asthma and idiopathic pulmonary fibrosis, aiming to categorize diseases more accurately and design targeted therapies. The ultimate goal is to enhance treatment effectiveness, minimize adverse events, and shift towards a patient-centered approach to managing respiratory conditions. Despite limitations, precision medicine holds promise for improving patient outcomes and emphasizing personalized care in respiratory medicine.

Management of intracranial cavernous malformations using conservative vs. surgical and/or radiosurgical treatment: A systematic review and meta­analysis.

Intracranial cavernous malformations (CMs) are vascular lesions with a high bleeding rate. At present, the debate regarding their treatment is still ongoing. The present systematic review and meta-analysis aimed to evaluate the safety of surgery or radiosurgery (SRS) for the management of CMs and to determine their potential outcomes compared with conservative treatment. The present systematic review and meta-analysis investigated the relative articles involving the management of intracranial CMs, namely their natural history (conservative treatment) vs. surgical/SRS treatment through electronic databases until June, 2023. The collected variables included the first author's name, the study period covered, the year of publication, the total number of patients examined and their age, and the number of males. In total, six articles met the eligibility criteria. The total number of patients was 399 (157 in the surgery/SRS group and 242 in the conservative treatment group). The results revealed that surgical or SRS management is a safe procedure for CMs compared with conservative treatment. Notably, the use of hemosiderin in the pre-MRI, the free of seizures parameter and the neurological deficit parameters were associated with improved outcomes in the surgical or SRS group of patients.

Exploring the pathogenetic mechanisms of Mycoplasmapneumoniae (Review).

Mycoplasmas, the smallest self-replicating prokaryotes without a cell wall, are the most prevalent and extensively studied species in humans. They significantly contribute to chronic respiratory tract illnesses and pneumonia, with children and adolescents being particularly vulnerable. Mycoplasma pneumoniae (M. pneumoniae) infections typically tend to be self-limiting and mild but can progress to severe or even life-threatening conditions in certain individuals. Extrapulmonary effects often occur without pneumonia, and both intrapulmonary and extrapulmonary complications operate through separate pathological mechanisms. The indirect immune-mediated damage of the immune system, vascular blockages brought on by vasculitis or thrombosis and direct harm from invasion or locally induced inflammatory cytokines are potential causes of extrapulmonary manifestations due to M. pneumoniae. Proteins associated with adhesion serve as the primary factor crucial for the pathogenicity of M. pneumoniae, relying on a specialized polarized terminal attachment organelle. The type and density of these host receptors significantly impact the adhesion and movement of M. pneumoniae, subsequently influencing the pathogenic mechanism and infection outcomes. Adjacent proteins are crucial for the proper assembly of the attachment organelle, with variations in the genetic domains of P1, P40 and P90 surfaces contributing to the variability of clinical symptoms and offering new avenues for developing vaccines against M. pneumoniae infections. M. pneumoniae causes oxidative stress within respiratory tract epithelial cells by adhering to host cells and releasing hydrogen peroxide and superoxide radicals. This oxidative stress enhances the vulnerability of host cells to harm induced by oxygen molecules. The lack of superoxide dismutase and catalase of bacteria allows it to hinder the catalase activity of the host cell, leading to the reduced breakdown of peroxides. Lung macrophages play a significant role in managing M. pneumoniae infection, identifying it via Toll-like receptor 2 and initiating the myeloid differentiation primary response gene 88-nuclear factor κΒ signaling cascade. However, the precise mechanisms enabling M. pneumoniae to evade intracellular host defenses remain unknown, necessitating further exploration of the pathways involved in intracellular survival. The present comprehensive review delves into the pathogenesis of M. pneumoniae infection within the pulmonary system and into extrapulmonary areas, outlining its impact.

Acute intracranial hemorrhage during the installation of the LICOX microdialysis system: A case report.

Neuro-monitoring is widely employed for the evaluation of intubated patients in the intensive care unit with stroke, severe head trauma, subarachnoid hemorrhage and/or hepatic encephalopathy. The present study reports the case of a patient with acute intracranial hemorrhage following the insertion of neuromonitoring catheters, which required surgical management. The patient was a 14-year-old male who sustained a severe traumatic brain injury and underwent a right-sided hemicraniectomy. During the installation of the neuromonitoring catheters, an acute hemorrhage was noted with a rapidly elevating intracranial pressure. A craniotomy was performed to identify and coagulate the injured cortical vessel. As demonstrated herein, the thorough evaluation of the clotting profile of the patient, a meticulous surgical technique and obtaining a post-insertion computed tomography scan may minimize the risk of any neuromonitoring-associated hemorrhagic complications.

Surgical outcomes of patients with unruptured anterior vs. inferior circulation aneurysms: A meta­analysis.

The treatment option for unruptured intracranial aneurysms (UIAs) depends on their natural history-related risk of rupture vs. the risk of surgical management. The present meta-analysis sought to assess the association between the surgical outcomes of anterior and posterior circulation UIAs. The present study investigated the comparative articles involving the surgical treatment of anterior vs. posterior circulation UIAs through electronic databases, including the Cochrane Library, PubMed (1980 to March, 2023), Medline (1980 to March, 2023) and EMBASE (1980 to March, 2023). Quoting all exclusion and inclusion criteria, nine articles finally remained for statistical analysis. The entire number of patients included in these nine articles was 3,253 (2,662 in the anterior and 591 in the posterior circulation UIAs group). The present meta-analysis proposes that the surgical treatment of anterior circulation UIAs is associated with better outcomes compared with the surgical management of posterior circulation UIAs.

Atypical pneumonia (Review).

Atypical pneumonia encompasses diverse pathogens, such as Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella species, which differ from typical bacterial pneumonia in their extrapulmonary manifestations. Clinical differentiation relies on systemic involvement rather than on standalone symptoms. Despite challenges in distinct diagnosis, syndromic approaches and weighted point systems aid in accurate presumptive diagnoses. Antibiotic treatment, often non-ß-lactams due to the unique cell structures of atypical pathogens, targets intracellular processes. Macrolides, tetracyclines, quinolones and ketolides are effective due to their intracellular penetration, crucial for combating these intracellular pathogens. The prevalence of atypical pneumonia varies globally, with Europe, Asia/Africa and Latin America reporting detection rates between 20-28%. Streptococcus pneumoniae remains a primary cause of pneumonia; however, atypical pathogens contribute significantly to this disease, being more prevalent in outpatient settings and among young adults. Legionella stands out in severe hospitalized cases and is associated with higher mortality rates. Diagnosis proves challenging due to overlapping symptoms with other respiratory infections. Differentiation among pathogens, such as Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella relies on subtle clinical variations and imaging findings. Diagnostic methods include serological studies, cultures and polymerase chain reaction, each with limitations in sensitivity or specificity. Prognosis varies widely. Atypical pneumonia can progress to severe forms with fatal outcomes, causing multi-organ damage. Complications extend beyond the respiratory system, affecting the cardiovascular system, exacerbating conditions such as chronic obstructive pulmonary disease and asthma, and potentially linking to conditions such as lung cancer. Increasing antibiotic resistance poses a significant challenge, influencing treatment outcomes and prolonging illness duration.

Gastric cancer and brain metastasis: A systematic review and meta­analysis.

Gastric cancer (GC) constitutes one of the most wide-ranging cancers, with brain metastasis (BM) being a markedly uncommon and unfavorable outcome. The present meta-analysis evaluated the relationship between no-surgical treatment vs. additional surgical BM resection on the patient's quality of life and potential survival using electronic databases, including PubMed (1980-April 2024), Medline (1980-April 2024), Cochrane Library, and EMBASE (1980-April 2024). After a literature search, six articles were included in the final study pool. The number of patients with BM and conservative treatment was 289 (80.05%) compared with those that underwent an additional surgical resection 72 (19.95%). The mean age was 59.2 years, and the males were 195 (73.8%) of 264 available from five studies. The findings of the present meta-analysis revealed that the curative effect of BM tumor resection on patients with GC undergoing additional treatment with stereotactic radiosurgery, whole-brain radiotherapy or chemotherapy was favorable for their survival.

Efficacy of decompressive craniectomy: A retrospective case series study with 321 patients and an update on controversies.

Decompressive craniectomy (DC) is considered a cornerstone in the management of refractory intracranial hypertension. For decades, DC was known as an occasionally lifesaving procedure; however, it was associated with numerous severe complications. The present study is a single-center retrospective case series study on with 321 patients who underwent DC between January, 2010 and December, 2020. All patients were divided into four groups as follows: Group A included patients who suffered from a space-occupying middle cerebral artery (MCA) ischemic event; group B included individuals who developed intracerebral hemorrhage; group C included patients admitted for traumatic brain injury; and group D included patients with other neurosurgical entities that underwent DC, such as subarachnoid hemorrhage, tumors, brain abscess and cerebral ventricular sinus thrombosis events. The present study enrolled a total of 321 patients who underwent DC. Group A included 52 out of the 321 (16.1%) patients, group B included 51 (15.8%) patients, group C included 164 (51.0%) patients, and group D included 54 (16.8%) patients. Of the 321 patients, 235 (73.2%) were males, and the median age was 53.7 years. Multivariate analysis revealed that only the group A parameter was an independent factor associated with a Glasgow outcome scale score >2 during follow-up (P<0.05). On the whole, the results of the present study suggest that among patients who underwent DC with different neurological entities, those who had experienced MCA events had more favorable outcomes.

Prevalence of ACA variations: A systematic review and meta­analysis.

The anterior cerebral artery (ACA) and its divisions enclose symptomatically critical and supplementary differentiations. Anatomical variations of the distal ACA that are irregularly detected can be separated into three major groups, namely, azygos, bihemispheric and median ACA variations. The present study performed a systematic review and meta-analysis. The PICOS criteria and electronic databases, namely the Cochrane Library, PubMed (until December, 2023), Embase (until December, 2023) and MEDLINE (until December, 2023) were used to identify 48 articles to fulfill the eligible criteria. As a limited number of studies exist on the prevalence of ACA anatomical variations, the present meta-analysis aimed to determine the precise incidence of these variants. In addition, with the comparative description between cadaveric (autopsy) and imaging cases, more accurate results were extract from the prevalence presentation of the distal ACA variants. On the whole, no statistically significant differences were found between autopsy and imaging studies.