Compressive lesions in the central nervous system of buffaloes / Lesões compressivas no sistema nervoso central de bubalinos

This study describes, through a retrospective study, the epidemiological and clinical-pathological findings of compression in the central nervous system (CNS) of buffaloes. The study includes observations made in 15 animals from 1998 to 2021 by reviewing the clinical records of animals with compressive injuries of the CNS treated at the Veterinary Hospital of the Veterinary Medicine Institute of the Federal University of Pará. The animals treated with clinical signs compatible with CNS compressive lesions were subjected to general and specific clinical examinations of the nervous system. Blood samples were collected from four animals for complete blood counts, and cerebrospinal fluid (CSF) samples were collected from three animals for physical evaluation. Thirteen animals were necropsied. The age range of the affected animals ranged from four months to 11 years of age, with a greater frequency over age 12 months (80%, 13/15). The most affected vertebral segment was between T3 and L3 (60%, 9/15), followed by brain injury (20%, 3/15), the L4-S2 segment (13.3%, 2/15) and the C1-C5 segment (6.7%, 1/15). The clinical findings varied according to the location of the lesion. The necropsy findings revealed paraypophyseal abscess in the brainstem and vertebral body, subarachnoid hematoma, lymphoma and vertebral fractures. The performance of a thorough clinical examination of the CNS combined with the necropsy findings was important to characterize the clinical picture and to locate the cause and the affected CNS segments in the buffaloes studied. It is important to include CNS compressive lesions among the neurological diseases of buffaloes.

Esse trabalho descreve, através de estudo retrospectivo, os achados epidemiológicos e clínico-patológicos de compressão no sistema nervoso central (SNC) de bubalinos. O estudo compreendeu as observações realizadas em 15 animais, durante os anos de 1998 a 2021, por meio da revisão dos arquivos de fichas clínicas de animais com lesões compressivas no SNC atendidos pelo Hospital Veterinário do Instituto de Medicina Veterinária da Universidade Federal do Pará. Os animais atendidos com sinais clínicos compatíveis com lesões compressivas no SNC foram submetidos a exames clínicos geral e específico do sistema nervoso. Foram coletadas amostras de sangue de quatro animais para realização de hemograma e amostras de líquido cefalorraquidiano (LCR) de três animais para avaliação física. Foram necropsiados 13 animais. A faixa etária dos animais acometidos variou de quatro meses a 11 anos de idade, com maior frequência na faixa acima de 12 meses (80%, 13/15). O segmento vertebral mais acometido foi entre T3-L3 (60%, 9/15), seguida por lesão no encéfalo (20%, 3/15), pelo segmento L4-S2 (13,3%, 2/15) e pelo segmento C1-C5 (6,7%, 1/15). Os achados clínicos variaram de acordo com a localização da lesão. Os achados de necropsia revelaram abscesso parahipofisário, no tronco encefálico e no corpo da vértebra, hematoma subaracnoidea, linfoma e fraturas vertebrais. A realização de um minucioso exame clínico do SNC associado aos achados de necropsia foram importantes para caracterizar o quadro clínico e localizar a causa e os seguimentos acometidos do SNC nos búfalos estudados. Torna-se importante incluir as lesões compressivas do SNC entre as enfermidades neurológicas dos bubalinos.

Compressive lesions in the central nervous system of cattle: a retrospective study of 50 cases in the Amazon biome / Lesões compressivas no sistema nervoso central de bovinos: um estudo retrospectivo de 50 casos no bioma amazônico

The present study gathered epidemiological and clinical-pathological information about cattle with compressive lesions in the central nervous system (CNS). The retrospective study included observations made in 50 cattle from 1998 to 2021 by reviewing the clinical records of animals with compressive lesions in the CNS treated at the Veterinary Hospital of the Veterinary Medicine Institute of the Federal University of Pará. The animals had clinical signs and were subjected to general and specific clinical examination of the nervous system. Blood samples were collected from 13 animals for complete blood counts, and cerebrospinal fluid (CSF) samples were collected from four animals for physical evaluation. Twenty-nine cattle underwent necropsy. The most affected sites were the T3-L3 (46%, 23/50), C1-C5 (22%, 11/50), C6-T2 (14%, 7/50), sacrococcygeal vertebrae, (4%, 2/50), L4-S2 (2%, 1/50), brain (8%, 4/50) and cerebellum (4%, 2/50). The age of the affected cattle ranged from 20 days to 16 years, with a higher occurrence in animals younger than 12 months (56%, 28/50). More Females were affected (58%, 29/50) than males (42%, 21/50). The clinical signs varied according to the location of the lesion and were mainly represented by ataxia, paresis or paralysis of the limbs, inability to stand and walk, postural changes, hyperesthesia in the extremities, and loss of skin sensitivity at the location of the lesion. The necropsy findings revealed changes such as abscesses in the vertebral body; intervertebral space in the medullary canal, pituitary and cerebellum; granuloma in the arch of the vertebra; fractures of the body of the vertebrae; subarachnoid haematoma; congenital bone alteration causing spinal cord compression; and spondylitis. Detailed anamnesis and clinical examination of the CNS, associated with necropsy findings, were important to determine the cause of the disease, correlate with the clinical picture and locate the affected segments of the CNS in the cattle. It is important to include these diseases in the list of differential diagnoses in cattle with nervous symptoms.

O presente trabalho reúne informações epidemiológicas e clínicopatológicas de bovinos com lesões compressivas no sistema nervoso central (SNC). O estudo retrospectivo compreendeu as observações realizadas em 50 bovinos durante os anos de 1998 a 2021, por meio da revisão dos arquivos de fichas clínicas de animais com lesões compressivas no SNC atendidos pelo Hospital Veterinário do Instituto de Medicina Veterinária da Universidade Federal do Pará. Os animais atendidos com sinais clínicos foram submetidos a exame clínico geral e específico do sistema nervoso. Foram coletadas amostras de sangue de 13 animais para realização de hemograma e amostras de líquido cefalorraquidiano de quatro animais para avaliação física. Foram submetidos à necropsia 29 bovinos. Os locais mais acometidos foram as vértebras T3-L3 (46%, 23/50), C1-C5 (22%, 11/50), C6-T2 (14%, 7/50), sacrococcígea (4%, 2/50) e L4-S2 (2%, 1/50); cérebro (8%, 4/50) e cerebelo (4%, 2/50). A idade dos bovinos afetados variou de 20 dias a 16 anos, com maior ocorrência em animais com menos de 12 meses (56%, 28/50). As fêmeas foram mais acometidas (58%, 29/50) do que os machos (42%, 21/50). Os sinais clínicos variaram de acordo com a localização da lesão e foram representados principalmente por ataxia, paresia ou paralisia dos membros, incapacidade de se levantar e de ficar em estação, alterações posturais, hiperestesia nas extremidades, além de perda da sensibilidade cutânea relacionada com a localização da lesão. Os achados de necropsia revelaram alterações como abscessos no corpo vertebral, no espaço intervertebral, no canal medular, para-hipofisário e no cerebelo; granuloma no arco da vértebra, fraturas do corpo das vértebras; hematoma subaracnoide; alteração óssea congênita causando compressão medular e espondilite. Anamnese detalhada e exame clínico do SNC, associados aos achados de necropsia foram importantes para determinar a causa da doença, correlacionar com o quadro clínico e localizar os segmentos acometidos do SNC dos bovinos. Torna-se importante incluir estas enfermidades na lista de diagnósticos diferenciais em bovinos que apresentem sintomatologia nervosa.

Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists.

Oxytocin (OT) and vasopressin (AVP) are hypothalamic neuropeptides classically associated with their regulatory role in reproduction, water homeostasis, and social behaviors. Interestingly, this role has expanded in recent years and has positioned these neuropeptides as therapeutic targets for various neuropsychiatric diseases such as autism, addiction, schizophrenia, depression, and anxiety disorders. Due to the chemical-physical characteristics of these neuropeptides including short half-life, poor blood-brain barrier penetration, promiscuity for AVP and OT receptors (AVP-R, OT-R), novel ligands have been developed in recent decades. This review summarizes the role of OT and AVP in neuropsychiatric conditions, as well as the findings of different OT-R and AVP-R agonists and antagonists, used both at the preclinical and clinical level. Furthermore, we discuss their possible therapeutic potential for central nervous system (CNS) disorders.

Central nervous system lesions caused by canine distemper virus in 4 vaccinated dogs.

We examined the cerebellum and cerebrum of 4 vaccinated dogs, 3-60-mo-old, that displayed clinical signs of canine distemper virus (CDV) infection, and died 7-40 d after developing neurologic signs. The main histologic lesions were demyelination, gliosis, meningitis, perivascular lymphocytic cuffing, and inclusion bodies. These lesions were similar in all 4 cases regardless of the time since vaccination, except that meningoencephalitis and gliosis were subacute in 3 dogs and chronic in 1 dog. However, these differences did not appear to be related to their vaccination status. Immunohistologically, a CDV-positive immunoreaction was seen mainly in astrocytes, neurons and their axons, lymphocytes around and in the blood vessels of the pia mater and choroid plexus, ependymal cells of each ventricle, and the cells of the choroid plexus. The histologic and immunohistologic changes were similar in the cerebellum and cerebrum. The genetic characterization of the virus strains in 2 of these naturally occurring canine distemper cases confirmed that they were South American wild-type strains (Kiki and Uy251) belonging to the EU1/SA1 lineage. These strains are not included in the commercial CDV vaccines available in Uruguay.

The Influence of Size and Chemical Composition of Silver and Gold Nanoparticles on in vivo Toxicity with Potential Applications to Central Nervous System Diseases.

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.

Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection.

The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on the immediate risks and impact on the respiratory system; however, the effects induced to the central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 infection can dramatically affect brain function and exacerbate neurodegenerative diseases in patients, but the mechanisms have not been entirely described. In this review, we gather information from past and actual studies on coronaviruses that informed neurological dysfunction and brain damage. Then, we analyzed and described the possible mechanisms causative of brain injury after SARS-CoV-2 infection. We proposed that potential routes of SARS-CoV-2 neuro-invasion are determinant factors in the process. We considered that the hematogenous route of infection can directly affect the brain microvascular endothelium cells that integrate the blood-brain barrier and be fundamental in initiation of brain damage. Additionally, activation of the inflammatory response against the infection represents a critical step on injury induction of the brain tissue. Consequently, the virus' ability to infect brain cells and induce the inflammatory response can promote or increase the risk to acquire central nervous system diseases. Here, we contribute to the understanding of the neurological conditions found in patients with SARS-CoV-2 infection and its association with the blood-brain barrier integrity.

[Trident sign in spinal cord neurosarcoidosis]. / Signo del tridente en la neurosarcoidosis medular.

TITLE: Signo del tridente en la neurosarcoidosis medular.

Updates in the Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes.

The disorders of the central nervous system associated with cancer by remote immune-mediated mechanisms are a heterogeneous group. These disorders encompass the classic paraneoplastic disorders and the recently recognized autoimmune encephalitis associated with antibodies against neuronal cell surface or synaptic proteins that occur with or without cancer association. In the last decade, the new surge of interest in neuronal diseases associated with anti-neuronal antibodies led to the rapid discovery of new forms of disease that have different manifestations and were not previously suspected to be immune mediated. The recognition of these syndromes is important because it may lead to early detection of an underlying malignancy and prompt initiation of treatment, improving chances for a better outcome.

Neurotoxicosis in horses associated with consumption of Trema micrantha.

BACKGROUND: Trema micrantha is a tree widely distributed throughout the Americas. The tree produces highly palatable leaves that have been associated with natural poisoning in goats, sheep and horses, in which hepatic necrosis and hepatic encephalopathy have been observed. OBJECTIVES: This study describes malacia and haemorrhage in the central nervous system (CNS) due to T. micrantha consumption, with minimal to absent hepatic lesions. STUDY DESIGN: Retrospective case series. METHODS: A total of 14 horses with a history of neurological signs and spontaneous consumption of T. micrantha leaves were submitted to necropsy and multiple samples were collected for histopathology. Details of clinical history and signs of the horses were obtained through inquiries to the owners and attending veterinarians. RESULTS: All the 14 horses had neurological signs of ataxia, severe sialorrhoea, involuntary running movements, sternal and lateral recumbency, and death after a clinical course that lasted from 24 h to 9 days. For a few days prior to onset of clinical signs, all horses had spontaneously consumed, potentially toxic doses of T. micrantha leaves. All 14 brains had diffuse yellowish discoloration affecting the rhombencephalon, mesencephalon, diencephalon, telencephalon and corpus striatum. In all cases, the most severe lesions were observed in the pons. Spinal cord lesions were observed affecting the lumbar intumescence, which was swollen with darken and depressed areas at the dorsal and ventral horns, and at the sacral level, which on cut surface displayed a friable and yellowish grey matter. The lesions observed grossly in brain and spinal cord consisted microscopically of severe vasculitis and liquefactive necrosis of white and grey matter of the brainstem, cerebellum and spinal cord. MAIN LIMITATIONS: This is a small retrospective series relying on clinical observations reported by owners and attending veterinarians. The mechanism of action of the plant toxin in the CNS is still unidentified. CONCLUSION: T. micrantha poisoning in horses causes predominantly a neurological disease, with minimal to absent hepatic lesions.

Balance between inflammatory and regulatory cytokines in systemic lupus erythematosus.

To investigate the cytokine profile in serum and cerebrospinal fluid (CSF) from patients with systemic lupus erythematosus (SLE) and central nervous system infection, we measured interferon-g (IFN-g), interleukin-1b (IL-1b), IL-4, IL-6, IL-8, IL-10, and IL-17 levels in serum and CSF from 50 SLE patients and 38 matched controls. In patients with active compared to quiescent disease, serum levels were higher for IL-1b (P = 0.042) and IL-17 (P = 0.041) but we found no significant correlation between IL-1b and IL-17 and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (r = 0.055, r = 0.219, respectively). IL-10 level in active patients was lower compared to that in quiescent controls (P = 0.032). When comparing specific disease manifestations, IL-1b levels in patients with fever (P = 0.035) and IL-6 (P = 0.048) and IL-8 (P = 0.048) levels in those showing nervous system involvement were higher than in controls. Based on MRI results, we found that only increased cerebral ischemia was associated with increased IFN-g levels (P = 0.009). In neuropsychiatric lupus erythematous patients, CSF levels of IL-6 (P = 0.002), IL-8 (P = 0.009), and IL-17 (P = 0.034) were significantly higher when compared with control patients. IL-10:IL-1b ratio in patients with moderate and quiescent disease was higher than in patients with disease activity (P = 0.000). Pro-inflammatory adaptive cytokines were elevated during disease flare, while regulatory mediators were elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may be targets for novel immunotherapeutic agents for managing autoimmune diseases.

Magnetic Resonance Imaging of Pediatric Neurologic Emergencies.

Although computed tomography is often the first line of imaging in the emergency setting, magnetic resonance imaging (MRI) is of increasing importance in the evaluation of central nervous system emergencies in the pediatric population. As such, it is necessary to understand the indications for which MRI may be necessary. This article reviews the unique pathophysiologic entities affecting the pediatric population and the associated MRI findings. Specifically, utility of emergent MRI and characteristic appearances of traumatic brain injury, traumatic spinal injury, nonaccidental trauma, arterial ischemic stroke, cerebral sinovenous thrombosis, stroke mimics, and central nervous system infections are described.

BBB-targeting, protein-based nanomedicines for drug and nucleic acid delivery to the CNS.

The increasing incidence of diseases affecting the central nervous system (CNS) demands the urgent development of efficient drugs. While many of these medicines are already available, the Blood Brain Barrier and to a lesser extent, the Blood Spinal Cord Barrier pose physical and biological limitations to their diffusion to reach target tissues. Therefore, efforts are needed not only to address drug development but specially to design suitable vehicles for delivery into the CNS through systemic administration. In the context of the functional and structural versatility of proteins, recent advances in their biological fabrication and a better comprehension of the physiology of the CNS offer a plethora of opportunities for the construction and tailoring of plain nanoconjugates and of more complex nanosized vehicles able to cross these barriers. We revise here how the engineering of functional proteins offers drug delivery tools for specific CNS diseases and more transversally, how proteins can be engineered into smart nanoparticles or 'artificial viruses' to afford therapeutic requirements through alternative administration routes.

Neuroprotective effects of lipoxin A4 in central nervous system pathologies.

Many diseases of the central nervous system are characterized and sometimes worsened by an intense inflammatory response in the affected tissue. It is now accepted that resolution of inflammation is an active process mediated by a group of mediators that can act in synchrony to switch the phenotype of cells, from a proinflammatory one to another that favors the return to homeostasis. This new genus of proresolving mediators includes resolvins, protectins, maresins, and lipoxins, the first to be discovered. In this short review we provide an overview of current knowledge into the cellular and molecular interactions of lipoxins in diseases of the central nervous system in which they appear to facilitate the resolution of inflammation, thus exerting a neuroprotective action.

Incontinentia pigmenti.

Incontinentia pigmenti is a rare genodermatosis in which the skin involvement occurs in all patients. Additionally, other ectodermal tissues may be affected, such as the central nervous system, eyes, hair, nails and teeth. The disease has a X-linked dominant inheritance pattern and is usually lethal to male fetuses. The dermatological findings occur in four successive phases, following the lines of Blaschko: First phase - vesicles on an erythematous base; second phase - verrucous hyperkeratotic lesions; third phase - hyperchromic spots and fourth phase - hypochromic atrophic lesions.

Incontinentia pigmenti

Incontinentia pigmenti is a rare genodermatosis in which the skin involvement occurs in all patients. Additionally, other ectodermal tissues may be affected, such as the central nervous system, eyes, hair, nails and teeth. The disease has a X-linked dominant inheritance pattern and is usually lethal to male fetuses. The dermatological findings occur in four successive phases, following the lines of Blaschko: First phase - vesicles on an erythematous base; second phase - verrucous hyperkeratotic lesions; third phase - hyperchromic spots and fourth phase - hypochromic atrophic lesions.

Pathogenesis and pathobiology of zoonotic brucellosis in humans.

Although human brucellosis has protean clinical manifestations, affected tissues usually exhibit signs of inflammation. The cellular and molecular bases of some immunopathological phenomena probably involved in the pathogenesis of infection with brucellae have been elucidated recently. Human osteoblasts and fibroblast-like synoviocytes produce cytokines, chemokines and matrix metalloproteinases in response to infection with brucellae and/or to stimulation by brucellae-infected monocytes. In turn, released cytokines promote the secretion of the metalloproteinases and induce osteoclastogenesis. These phenomena may underlie the bone loss and cartilage degradation found in brucellar arthritis and osteomyelitis. Brucella abortus and its lipoproteins elicit an inflammatory response in the central nervous system of mice, leading to astrogliosis, a characteristic feature of neurobrucellosis. Brucellae can also replicate in human endothelial cells, inducing an inflammatory response with increased expression of chemokines, interleukin-6 and adhesion molecules. Persistent brucellar infection of the endothelium would support development of endocarditis and other vascular manifestations. Thus, although the inflammatory phenomena triggered by brucellae are relatively mild, they are long-lasting as a result of the prolonged intracellular persistence of the bacteria in infected tissues and eventually lead to tissue damage.