Validation of Tenths Stereotactic Coordinates Method Using Probabilistic Tractography of the Ansa Lenticularis in Parkinson's Disease Patients.

OBJECTIVE: To evaluate the accuracy of stereotactic coordinates to target the ansa lenticularis (AL) using 2 surgical planning methods, the conventional millimeter method (MM) and the normalized Tenths method (TM), assessed through individualized probabilistic tractography. METHODS: Stereotactic targeting of the AL was assessed in 2 groups: 16 patients with Parkinson's disease and 16 healthy controls from Group 1, and 39 Parkinson's disease patients from Group 2. Structural and diffusion magnetic resonance imaging probabilistic tractography identified the AL based on the Schaltenbrand-Wahren Atlas. The MM defined stereotactic coordinates in millimeters, while the TM refined the planning by dividing the intercommissural line (AC-PC) distance into 10 equal parts, normalizing the "X," "Y," and "Z" coordinates for each patient. We subsequently compared the percentage of structural connectivity (%conn) of the AL with predefined regions of interest (ROIs), including the frontopontine-corticothalamic tracts, globus pallidus internus-ventral oral anterior, and ventral oral posterior, and quantified the streamlines in 142 brain hemispheres using the MM and TM coordinates. RESULTS: Despite anatomical variations in intercommissural (AC-PC) line lengths between both groups (22.5 ± 2.09 mm and 24.4 ± 2.56 mm, respectively; P = 0.002), as well as differences in magnetic resonance imaging acquisition parameters, we found that the TM significantly enhanced streamline identification and %conn compared to the MM. These enhancements were noted across ROIs: frontopontine-corticothalamic and globus pallidus internus-ventral oral anterior in both hemispheres, and globus pallidus internus-ventral oral posterior in the left (P < 0.001) and right hemispheres (P = 0.03). CONCLUSIONS: TM surpasses MM in identifying the structural connectivity between the AL and predefined ROIs, underscoring the advantages of coordinate normalization. However, variations in AC-PC line lengths and Euclidean distances between methods could lead to inaccuracies in the coordinate settings, potentially affecting the precision of structural connectivity and the efficacy of therapeutic outcomes.

Factors associated with outcomes following microvascular decompression for the treatment of primary trigeminal neuralgia in adults: a systematic review and meta-analysis.

This study aimed to evaluate pain assessment strategies and factors associated with outcomes after microvascular decompression for the treatment of primary trigeminal neuralgia in adults. We conducted a systematic review and meta-analysis of English, Spanish, and French literature. We searched three databases, PubMed, Ovid, and EBSCO, from 2010 to 2022 and selected studies including patients with primary trigeminal neuralgia, clear pain assessment, and pain outcomes. Population means and standard deviations were calculated. Studies that included factors associated with postoperative outcomes were included in the meta-analysis. A total of 995 studies involving 5673 patients with primary trigeminal neuralgia following microvascular decompression were included. Patients with arteries compressing the trigeminal nerve demonstrated optimal outcomes following microvascular decompression (odds ratio [OR]= 0.39; 95% confidence interval [CI] = 0.19-0.80; X2 = 46.31; Dof = 15; I2 = 68%; P = < 0.0001). Conversely, when comparing arterial vs venous compression of the trigeminal nerve (OR = 2.72; 95% CI = 1.16-6.38; X2 = 23.23; Dof = 10; I2 = 57%; P = 0.01), venous compression demonstrated poor outcomes after microvascular decompression. Additionally, when comparing single-vessel vs multiple-vessel compression (OR = 2.72; 95% CI = 1.18-6.25; X2 = 21.17; Dof = 9; I2 = 57%; P = 0.01), patients demonstrated unfavorable outcomes after microvascular decompression. This systematic review and meta-analysis evaluated factors associated with outcomes following microvascular decompression (MVD) for primary trigeminal neuralgia (PTN). Although MVD is an optimal treatment strategy for PTN, a gap exists in interpreting the results when considering the lack of evidence for most pain assessment strategies.

Neurosurgical therapy possibilities in treatment of Huntington disease: An update.

INTRODUCTION: Huntington's disease (HD) is a hereditary condition caused by the expansion of the CAG trinucleotide in the huntingtin gene on chromosome 4, resulting in motor, cognitive, and psychiatric disorders that significantly impact patients' quality of life. Despite the lack of effective treatments for the disease, various surgical strategies have been explored to alleviate symptoms and slow its progression. METHODOLOGY: A comprehensive systematic literature review was conducted, including MeSH terms, yielding only 38 articles that were categorized based on the surgical procedure. The study aimed to describe the types of surgeries performed and their efficacy in HD patients. RESULTS: Deep brain stimulation (DBS) involved 41 predominantly male patients with bilateral implantation in the globus pallidus, showing a preoperative Unified Huntington's Disease Rating Scale (UHDRS) score of 60.25 ± 16.13 and a marked postoperative value of 48.54 ± 13.93 with a p < 0.018 at one year and p < 0.040 at three years. Patients experienced improvement in hyperkinesia but worsening of bradykinesia. Additionally, cell transplantation in 119 patients resulted in a lower preoperative UHDRS score of 34.61 ± 14.61 and a significant postoperative difference of 32.93 ± 15.87 (p < 0.016), respectively, in the first to third years of following. Some now, less used procedures were crucial for understanding brain function, such as pallidotomies in 3 patients, showing only a 25 % difference from their baseline. CONCLUSION: Despite advancements in technology, there is still no curative treatment, only palliative options. Promising treatments like trophic factor implantation offer new prospects for the future.

Dentate nucleus: a review and implications for dentatotomy.

PURPOSE: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. METHODS AND RESULTS: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. CONCLUSIONS: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.

Risk factors contributing to infection with SARS-CoV-2 are modulated by sex.

Throughout the early stages of the COVID-19 pandemic in Mexico (August-December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2.

Corrigendum: Deep brain stimulation neuromodulation for the treatment of mood disorders: obsessive compulsive disorder and treatment resistant depression.

[This corrects the article DOI: 10.3389/fpsyt.2021.764776.].

Minimally Invasive Retrosigmoidal Parasterional Burr-Hole Approach: Technique and Neuropathic Pain Amelioration after Microvascular Decompression of the Trigeminal Nerve.

BACKGROUND: Trigeminal neuralgia, a common condition in clinical practice, often occurs due to vascular compression caused by aberrant or ectopic arterial or venous vessels. Microvascular decompression through a minimally invasive retrosigmoidal approach has shown high rates of pain control, low complication rates, and excellent therapeutic results. OBJECTIVE: To describe the surgical technique and clinical outcomes in terms of pain relief after microvascular decompression of the trigeminal nerve through a minimally invasive retrosigmoidal parasterional burr-hole technique. METHODS: A group of patients with trigeminal neuralgia refractory to medical management who underwent microvascular decompression were examined. The records of the patients were considered retrospectively (2016-2018), and the outcomes were considered based on the Visual Analogue Scale (VAS) and the Barrow Neurological Institute Pain Scale (BNIPS) added to a technical note of the surgical technique for a minimally invasive retrosigmoidal parasterional burr-hole. RESULTS: Twenty-two patients were evaluated, and clinical assessment after surgical intervention showed a decrease in pain according to the VAS, resulting from an average preoperative state of 9.5 ± 0.37 to a postoperative condition of 1.32 ± 1.28, exhibiting statistically significant changes (p < 0.0001, d = 9.356). On the other hand, in relation to the BNIPS scale, a decrease from an average preoperative status of 4.55 ± 0.25 to a postoperative status at 12 months of 1.73 ± 0.54 was also demonstrated, showing significant changes (p < 0.0001, d = 3.960). CONCLUSION: Microvascular decompression of the trigeminal nerve through a minimally invasive retrosigmoidal parasterional burr-hole is feasible and can be a safe and effective technique for the management of pain. However, further research employing larger sample sizes and longer follow-up periods is necessary.

Neurological Diseases Define the Cytokine Profile in CFS during SARS-CoV-2 Infection in Highly Ill Patients.

Neuroinflammation is critical in developing and progressing neurological diseases. The underlying pro-inflammatory cytokine expression combined with additional mechanisms in the neuropathology, such as oxidative stress, brain-blood barrier damage, and endothelial dysfunction, could contribute to the susceptibility to developing severe COVID-19. The physiopathology of SARS-CoV-2 and other human coronaviruses (H-CoVs) has not been completely understood; however, they have all been linked to a disproportionated response of the immune system, particularly an exacerbated cytokine production and the dysregulation of total cell counts. In this article, based on the compilation of studies reported by our working group regarding COVID-19 and neurological diseases, we propose that the inflammation observed in the central nervous system, through a CSF analysis, could be conditioned by neurological disease(s) and enhanced by COVID-19. Therefore, it is necessary to determine the cytokine profile in different neurological disorders to propose adequate treatments and avoid severe forms of the disease in these patients.

Innovative perspectives in limbic surgery using deep brain stimulation.

Limbic surgery is one of the most attractive and retaken fields of functional neurosurgery in the last two decades. Psychiatric surgery emerged from the incipient work of Moniz and Lima lesioning the prefrontal cortex in agitated patients. Since the onset of stereotactic and functional neurosurgery with Spiegel and Wycis, the treatment of mental diseases gave attention to refractory illnesses mainly with the use of thalamotomies. Neurosis and some psychotic symptoms were treated by them. Several indications when lesioning the brain were included: obsessive-compulsive disorder, depression, and aggressiveness among others with a diversity of targets. The indiscriminately use of anatomical sites without enough scientific evidence, and uncertainly defined criteria for selecting patients merged with a deficiency in ethical aspects, brought a lack of procedures for a long time: only select clinics allowed this surgery around the world from 1950 to the 1990s. In 1999, Nuttin et al. began a new chapter in limbic surgery with the use of Deep Brain Stimulation, based on the experience of pain, Parkinson's disease, and epilepsy. The efforts were focused on different targets to treat depression and obsessive-compulsive disorders. Nevertheless, other diseases were added to use neuromodulation. The goal of this article is to show the new opportunities to treat neuropsychiatric diseases.

Opportune warning of COVID-19 in a Mexican health care worker cohort: Discrete beta distribution entropy of smartwatch physiological records.

We present a statistical study of heart rate, step cadence, and sleep stage registers of health care workers in the Hospital General de México "Dr. Eduardo Liceaga" (HGM), monitored continuously and non-invasively during the COVID-19 contingency from May to October 2020, using the Fitbit Charge 3® Smartwatch device. The HGM-COVID cohort consisted of 115 participants assigned to areas of COVID-19 exposure. We introduce a novel biomarker for an opportune signal for the likelihood of SARS-CoV-2 infection based on the Shannon Entropy of the Discrete Generalized Beta Distribution fit of rank ordered smartwatch registers. Our statistical test indicated infection for 94% of patients confirmed by positive polymer chain reaction (PCR+) test, 47% before the test, and 47% in coincidence. These results required innovative data preprocessing for the definition of a new biomarker index. The statistical method parameters are data-driven, confidence estimates were calibrated based on sensitivity tests using appropriately derived surrogate data as a benchmark. Our surrogate tests can also provide a benchmark for comparing results from other anomaly detection methods (ADMs). Biomarker comparison of the negative Immunoglobulin G Antibody (IgG-) subgroup with the PCR+ subgroup showed a statistically significant difference (p < 0.01, effect size = 1.44). The distribution of the uninfected population had a lower median and less dispersion than the PCR+ population. A retrospective study of our results confirmed that the biomarker index provides an early warning of the likelihood of COVID-19, even several days before the onset of symptoms or the PCR+ test request. The method can be calibrated for the analysis of different SARS-CoV-2 strains, the effect of vaccination, and previous infections. Furthermore, our biomarker screening could be implemented to provide general health profiles for other population sectors based on physiological signals from smartwatch wearable devices.

Current concepts of pain pathways: a brief review of anatomy, physiology, and medical imaging.

BACKGROUND: Although the essential components of pain pathways have been identified, a thorough comprehension of the interactions necessary for creating focused treatments is still lacking. Such include more standardised methods for measuring pain in clinical and preclinical studies and more representative study populations. OBJECTIVE: This review describes the essential neuroanatomy and neurophysiology of pain nociception and its relation with currently available neuroimaging methods focused on health professionals responsible for treating pain. METHODS: Conduct a PubMed search of pain pathways using pain-related search terms, selecting the most relevant and updated information. RESULTS: Current reviews of pain highlight the importance of their study in different areas from the cellular level, pain types, neuronal plasticity, ascending, descending, and integration pathways to their clinical evaluation and neuroimaging. Advanced neuroimaging techniques such as fMRI, PET, and MEG are used to better understand the neural mechanisms underlying pain processing and identify potential targets for pain therapy. CONCLUSIONS: The study of pain pathways and neuroimaging methods allows physicians to evaluate and facilitate decision-making related to the pathologies that cause chronic pain. Some identifiable issues include a better understanding of the relationship between pain and mental health, developing more effective interventions for chronic pain's psychological and emotional aspects, and better integrating data from different neuroimaging modalities for the clinical efficacy of new pain therapies.

Rate of residual neuromuscular block using single-dose rocuronium in general anesthesia for ENT surgery: a retrospective cohort study.

INTRODUCTION: NMB facilitates intubating conditions in general anesthesia. However, it is associated with significant residual postoperative paralysis and morbidity. OBJECTIVE: To investigate the rate of underdiagnosed residual NMB based on two TOFR criteria (< 0.91 and < 1.00). METHODS: We performed a retrospective study adhering to STROBE guidelines. We included patients undergoing ENT surgery using single-dose neuromuscular block for balanced general anesthesia from June to December 2018. We collected demographic and anthropometric data, ASA score, NMBA dose, TOFR recordings at 5, 30 and 60 min and end of the surgery, anesthesia and surgery time, and administration of reversal agent. Statistical analysis included descriptive and dispersion measures statistics, curve and cross tables for residual NMB on different TOFR criteria with sub-analysis for AR, RR, and OR in patients over 65 years old. RESULTS: We included 57 patients, mean age 41; 43 females and 14 males. Mean anesthetic and surgical time were 139.4 and 116.1 min, respectively. All the patients received rocuronium under a mean ponderal single-dose of 0.48 mg/kg. Residual NMB rates were 29.9 and 49.1% for a TOFR < 0.91 and < 1.00, respectively. Older adults had an OR of 6.08 for residual NMB. CONCLUSIONS: The rate of residual NMB was 29.9 to 49.1%, depending on the criteria used (TOFR < 0.91 and < 1.00, respectively). Patients above 65 years old had an increased risk of residual NMB (6.08 OR) and clinical symptoms related to residual NMB (11.75 OR). We recommend future research aiming to provide a specific surveillance protocol for patients above 65 years old, including shorter-action NMB, early reversal, and prolonged surveillance using the TOFR criteria of < 1.00 to identify patients at risk of residual NMB readily.

WHO CNS5 2021 includes specific mutations in gliomas that can be identified with MRI quantitative biomarkers.

In 2021, the latest version of the World Health Organization classification of central nervous system tumors (WHO CNS5) was published, which is considered an international standard. The first editions of this classification were based on histological characteristics and, subsequently, aspects related to new knowledge were incorporated. In the 2016 revision, molecular characteristics were implemented for the classification and staging of gliomas, such as the presence of mutations in IDH1 or IDH2. Currently, advanced magnetic resonance imaging (MRI) techniques allow assessing for the presence of 2-HG (increased oncometabolite that precedes IDH mutations), whereby IDH mutations can be indirectly identified, without invasive procedures being required. Advanced MRI is a growing field, highly useful for diagnosis and management of different pathologies. This document addresses the implications of WHO CNS5 classification in the evaluation of gliomas, as well as historical aspects, the bases of conventional MRI, and advanced MRI sequences useful in current classification.

En 2021 se publicó la última versión de la clasificación de tumores del sistema nervioso central de la Organización Mundial de la Salud (WHO CNS5 por sus siglas en inglés), considerada un estándar internacional. Las primeras ediciones se basaron en características histológicas y posteriormente se incorporaron aspectos relacionados con nuevos conocimientos. En la revisión de 2016 se implementaron características moleculares para la clasificación y estadificación de los gliomas, como la presencia de mutaciones en IDH1 y IDH2. Actualmente, las técnicas de resonancia magnética avanzada permiten valorar la presencia de 2-HG (oncometabolito incrementado ante mutaciones en IDH), de forma que indirectamente y sin procedimientos invasivos pueden identificarse las mutaciones en IDH. La resonancia magnética avanzada es un procedimiento aún en desarrollo, de gran utilidad para el diagnóstico y manejo de distintas patologías. En el presente documento se abordan las implicaciones de la WHO CNS5 en la evaluación de gliomas, así como aspectos históricos, las bases de la resonancia magnética convencional y secuencias de resonancia magnética avanzada útiles en la clasificación actual.

WHO CNS5 2021 incluye mutaciones específicas en gliomas que pueden ser identificadas con biomarcadores cuantitativos de resonancia magnética / WHO CNS5 2021 includes specific mutations in gliomas that can be identified with MRI quantitative biomarkers

Resumen En 2021 se publicó la última versión de la clasificación de tumores del sistema nervioso central de la Organización Mundial de la Salud (WHO CNS5 por sus siglas en inglés), considerada un estándar internacional. Las primeras ediciones se basaron en características histológicas y posteriormente se incorporaron aspectos relacionados con nuevos conocimientos. En la revisión de 2016 se implementaron características moleculares para la clasificación y estadificación de los gliomas, como la presencia de mutaciones en IDH1 y IDH2. Actualmente, las técnicas de resonancia magnética avanzada permiten valorar la presencia de 2-HG (oncometabolito incrementado ante mutaciones en IDH), de forma que indirectamente y sin procedimientos invasivos pueden identificarse las mutaciones en IDH. La resonancia magnética avanzada es un procedimiento aún en desarrollo, de gran utilidad para el diagnóstico y manejo de distintas patologías. En el presente documento se abordan las implicaciones de la WHO CNS5 en la evaluación de gliomas, así como aspectos históricos, las bases de la resonancia magnética convencional y secuencias de resonancia magnética avanzada útiles en la clasificación actual.

Abstract In 2021, the latest version of the World Health Organization classification of central nervous system tumors (WHO CNS5) was published, which is considered an international standard. The first editions of this classification were based on histological characteristics and, subsequently, aspects related to new knowledge were incorporated. In the 2016 revision, molecular characteristics were implemented for the classification and staging of gliomas, such as the presence of mutations in IDH1 or IDH2. Currently, advanced magnetic resonance imaging (MRI) techniques allow assessing for the presence of 2-HG (increased oncometabolite that precedes IDH mutations), whereby IDH mutations can be indirectly identified, without invasive procedures being required. Advanced MRI is a growing field, highly useful for diagnosis and management of different pathologies. This document addresses the implications of WHO CNS5 classification in the evaluation of gliomas, as well as historical aspects, the bases of conventional MRI, and advanced MRI sequences useful in current classification.

Trephinations, Trephines, and Craniectomies: Contrast Between Global Ancient Civilizations and Pre-Hispanic Mexican Cultures.

Mesoamerica is culturally rich in diverse aspects, such as nature, sociology, and archeology. Several neurosurgical techniques were described during the Pre-Hispanic era. In Mexico, various cultures, such as the Aztec, Mixtec, Zapotec, Mayan, Tlatilcan, and Tarahumara, developed surgical procedures using different tools to perform cranial and probably brain interventions. Trepanations, trephines, and craniectomies are different concepts utilized to describe skull operations, which were conducted to treat traumatic, neurodegenerative, and neuropsychiatric diseases, and as a prominent form of ritual practice. More than 40 skulls have been rescued and studied in this region. In addition to written medical sources, archeological vestiges allow a more profound comprehension of Pre-Columbian brain surgery. The purpose of this study is to present the existing evidence of cranial surgery in Pre-Hispanic Mexican civilizations and their worldwide counterparts, procedures that have contributed to the global neurosurgical armamentarium, and have significantly impacted the medical practice's evolution.

Prognostic factors of unilateral prelemniscal radiations radiofrequency lesions: A surgical technique for the treatment of Parkinson's disease motor symptoms.

OBJECTIVE: A group of patients with Parkinson's disease (PD) were managed with unilateral prelemniscal radiation radiofrequency lesions (U-Raprl). The current study aims to evaluate prognostic factors that could influence clinical response. METHODS: Patients previously diagnosed with PD managed with U-Raprl were included in the study, classifying them into two groups according to their percentage of clinical response ( 1.5), Age (p < 0.0001, ∆ = 2.38), Evolution (p < 0.0001, ∆ = 2.38), and post-operative UPDRS (p < 0.01, ∆ = 1.38). The qualitative analysis of the distribution regarding the responder group shows that those patients with an age under 58 years, an evolution fewer than 7 years, and a preoperative HYS score smaller than 2, showed a response ≥ 50% according to the UPDRS-III in all cases. CONCLUSION: U-Raprl is a highly effective procedure with a 5-year persistence of improvement. The most relevant prognostic factors to consider for a clinical response according to UPDRS-III greater than 50% are age under 58 years, less than 7 years of PD evolution, and HYS less or equal to 3.

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations.

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

Blood-brain Barrier Damage is Pivotal for SARS-CoV-2 Infection to the Central Nervous System.

Transsynaptic transport is the most accepted proposal to explain the SARS-CoV-2 infection of the CNS. Nevertheless, emerging evidence shows that neurons do not express the SARS-CoV-2 receptor ACE2, which highlights the importance of the blood-brain barrier (BBB) in preventing virus entry to the brain. In this study, we examine the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) and the cytokine profile in cerebrospinal fluids (CSF) from two patients with a brain tumor and COVID-19. To determine the BBB damage, we evaluate the Q- albumin index, which is an indirect parameter to assess the permeability of this structure. The Q-albumin index of the patient with an intraventricular brain tumor suggests that the BBB is undamaged, preventing the passage of SARS-CoV-2 and pro-inflammatory molecules. The development of brain tumors that disrupt the BBB (measured by the Q-albumin index), in this case, a petroclival meningioma (Case 1), allows the free passage of the SARS-CoV-2 virus and probably lets the free transit of pro-inflammatory molecules to the CNS, which leads to a possible activation of the microglia (astrogliosis) and an exacerbated immune response represented by IL-13, IFN-γ, and IL-2 trying to inhibit both the infection and the carcinogenic process.