Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage.

Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke nervous tissue damage due to the inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces the release of inflammatory mediators and damage molecules, which are then released into the bloodstream and can interact with structures such as the CNS, thus modifying the blood-brain barrier's (BBB´s) and blood-cerebrospinal fluid barrier´s (BCSFB´s) function and inducing aseptic neuroinflammation. During neuroinflammation, the participation of glial cells (astrocytes, microglia, and oligodendrocytes) plays an important role. They release cytokines, chemokines, reactive oxygen species, nitrogen species, peptides, and even excitatory amino acids that lead to neuronal damage. The neurons undergo morphological and functional changes that could initiate functional alterations to neurodegenerative processes. The present work aims to explain these processes and the pathophysiological interactions involved in CNS damage in the absence of microbes or inflammatory cells.

Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model.

Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.

Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis.

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Neurophysiological intraoperative monitoring during an optic nerve schwannoma removal.

This paper reports the case of a patient with optic nerve schwannoma and the first use of neurophysiological intraoperative monitoring of visual evoked potentials during the removal of such tumor with no postoperative visual damage. Schwannomas are benign neoplasms of the peripheral nervous system arising from the neural crest-derived Schwann cells, these tumors are rarely located in the optic nerve and the treatment consists on surgical removal leading to high risk of damage to the visual pathway. Case report of a thirty-year-old woman with an optic nerve schwannoma. The patient underwent surgery for tumor removal on the left optic nerve through a left orbitozygomatic approach with intraoperative monitoring of left II and III cranial nerves. We used Nicolet Endeavour CR IOM (Carefusion, Middleton WI, USA) to performed visual evoked potentials stimulating binocularly with LED flash goggles with the patient´s eyes closed and direct epidural optic nerve stimulation delivering rostral to the tumor a rectangular current pulse. At follow up examinations 7 months later, the left eye visual acuity was 20/60; Ishihara score was 8/8 in both eyes; the right eye photomotor reflex was normal and left eye was mydriatic and arreflectic; optokinetic reflex and ocular conjugate movements were normal. In this case, the epidural direct electrical stimulation of optic nerve provided stable waveforms during optic nerve schwannoma resection without visual loss.

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor ß (ß-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood.

Calcified Pilocytic Astrocytomas and Calcifying Pseudoneoplasms of the Neuraxis: A Diagnostic Challenge.

Pilocytic astrocytoma (PA), recognized as the most prevalent central nervous system (CNS) tumor, has long been associated with calcifications, a characteristic often attributed to benign or indolent growth patterns. In this study, we explored the calcified attributes in these tumors that beckon a deeper understanding. This is a retrospective study, on a set of seven cases, with a histopathological diagnosis of pilocytic astrocytoma with calcifications and psammoma bodies (PB). Despite an encouraging overall survival outcome, the recurrence in four cases cast some doubt on the conventional classification. The histological study of these cases revealed a spectrum of calcifications, varying in size and morphology, all of which exhibited positive reactivity to glial fibrillary acidic protein (GFAP), osteoconduction, and osteopontin. Notably, the immunohistochemistry showed hyaline bodies displaying an atypical immune profile, strikingly negative for vimentin and GFAP, and a robust positivity for epidermal growth factor receptors (EGFR), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1ß). These results stimulated speculation that the identity of these calcified tumors may have extended and potentially embraced the realm of calcifying pseudoneoplasms of the neuraxis (CAPNON), underscored by intense pilot gliosis. This study transcends mere anatomical exploration; it delves into the intricacies of calcified tumors, casting a spotlight on the dynamic interplay between PA and CAPNON. As we traverse the frontiers of neuro-oncology, these findings pave the way for innovative avenues in the diagnostics and therapeutics of these tumors.

Stem Cell Markers in Neoplasms and their Relationship with Progression-free and Overall Survival in Patients with Recurrence.

BACKGROUND: Gliomas account for 30% of primary brain tumors in adults, and despite the scientific progress in the field, recurrence is prevalent. Glioma Stem Cells (GSCs) can generate tumor cells in vivo and in vitro and they are associated with treatment resistance, tumor progression, and recurrence. Furthermore, the expression of SOX transcription factors (SOX1, SOX2, SOX9) in these cells is responsible for maintaining an oncogenic genotype and is associated with an aggressive tumor phenotype. The relationship between SOX transcription factors and their prognostic role in recurrent gliomas has not been described in detail. Therefore, we set out to describe the relationship between SOX expression and Progression-free Survival (PFS) and Overall Survival (OS) in patients with recurrent gliomas. METHODS: In this observational study, we have retrospectively analyzed 69 patients, of which 20 met the inclusion criteria. The clinical, radiological, and histopathological findings have been described, and survival analysis has been performed according to SOX expression for PFS and OS. RESULTS: We found SOX1, SOX2, and SOX9 to show a non-statistically significant trend with increasing histopathological grade, co-expressed with Ki67, a cell proliferation factor. CONCLUSION: There has been found an inversely proportional correlation between the degree of immunopositivity of SOX1 and OS. A higher SOX1 immunopositivity could predict a worse clinical prognosis. There has also been found an interaction between a pluripotent genotype (GSC) and cell proliferation.

Papillary Tumor of the Pineal Gland: Series of Four Clinical Cases.

The papillary tumor of the pineal region (PTPR) is a rare neuroepithelial tumor originating from specialized ependymocytes. It primarily affects structures within the pineal region, including the pineal gland, epithalamus, quadrigeminal cistern, and posterior wall of the third ventricle. Here, we present a series of four cases characterized by symptoms associated with obstructive hydrocephalus such as headaches, seizures, visual disturbances, gait disturbances, and Parinaud syndrome. Imaging studies revealed lesions in the pineal region, prompting surgical intervention. Histopathological examination, including biopsy and intraoperative analysis, confirmed the diagnosis of PTPR. Despite advancements, the etiology and pathogenesis of PTPR remain incompletely understood, warranting further research to refine management strategies.

Neuro-Behçet With a Thalamic Lesion: A Case Report.

Behçet's disease (BD) is an autoimmune disease characterized by multisystemic variable-vessel vasculitis and oral, genital, and intestinal ulcers. Neurological involvement or "Neuro-Behçet" (NB) manifests due to parenchymal inflammation. We present the case of a 21-year-old male with a five-year-old history of intermittent chronic oral and genital ulcers who presented with headache, right hemiparesis, progressive loss of visual acuity, and a thalamic tumor-like lesion on magnetic resonance imaging (MRI). A brain biopsy showed multiple perivascular infarcts associated with vasculitis affecting arterioles, venules, and capillaries.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis With Diffuse Demyelinating Plaques: A Case Report of an Atypical Presentation.

Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an autoimmune disease triggered by antibodies against the NR1 subunit of this receptor. It has a wide variety of presentations, including abnormal behavior, psychosis, seizures, abnormal movement, insomnia, and irritability. The diagnosis is confirmed by the presence of one of the six main symptoms and anti-NR1 immunoglobulin G (IgG)-positive antibodies in the cerebrospinal fluid (CSF) after the exclusion of other disorders. We present a case of an 18-year-old female with progressive paresthesia and muscle weakness that compromised walking and psychiatric symptoms. She was admitted to a private institution where magnetic resonance imaging (MRI) revealed pseudotumoral lesions, which led to surgical intervention. The original histopathological diagnosis was of a pleomorphic xanthoastrocytoma (PXA) WHO grade 2. As symptoms persisted, she was referred to our institution where a new MRI was performed, and a biopsy was re-evaluated. It showed perivascular inflammatory infiltrates composed of T cells, intense peripheral gliosis, nodules of macrophages, and reactive astrocytes in the white matter with fragmentation and vacuolation of myelin sheets, suggesting a demyelinating process in contrast to neoplasia. CSF analysis was performed, and it was positive for anti-NMDA antibodies. Immunohistochemical positivity for N-methyl-D-aspartate (NMDA) was observed in the neuronal nuclei, which led to the diagnosis.

Schwannoma and Post-vaccine Changes: A Case Report.

Schwannomas are benign sheaths of Schwann cells that can present with degenerative and morphological changes; necrosis or hemorrhage are rare findings in these tumors. We present the case of a 28-year-old man with a C2-C4 cervical Schwannoma who experienced upper limb paresthesia in 2020 while presenting with COVID-19 symptoms. The patient later recovered and came to our institution, where surgery was scheduled one year after the initial diagnosis. One week before surgery, the patient received the first dose of the Moderna vaccine. Despite being asymptomatic, the patient underwent successful total resection of the schwannoma, which was confirmed histologically. However, extensive necrosis with abundant foamy macrophages was observed, suggesting a possible link to post-vaccine effects.

Microsurgical Resection of a Giant Trochlear Nerve Schwannoma: 2-Dimensional Operative Video.

We present the case of a 17-year-old male, who complained of a 1-year onset of pulsatile headache, dysphagia, speech changes, and emotional lability. Neuroimaging revealed a large left-sided contrast-enhancing tumor located at the infratentorial space consistent with a large trochlear nerve schwannoma. The tumor was compressing the brainstem, obstructing the outflow of the third and lateral ventricles causing hydrocephalus, and disturbing the cortico-bulbar pathways bilaterally leading to the diagnosis of pseudobulbar palsy. After the patient consented the surgical procedure, he was operated through a subtemporal transtentorial approach placed in the lateral position. A lumbar drain was used for brain relaxation during the procedure and image guidance to define the limits of surgical exposure. A microsurgical technique was used, aiming to preserve the cranial nerves and the vascular structures running through the perimesencephalic cisterns. Gross total resection was achieved and clinical course remained uneventful aside from a transient third nerve palsy. Symptoms improved and the three-month follow-up revealed an almost complete function of the oculomotor nerve (Video 1). Trochlear nerve schwannomas are the rarest variety of the cranial nerve schwannomas. Depending on tumor size, clinical and neuroimaging signs of mass effect and brainstem compression, treatment can be observation, microsurgical resection through cranial base approaches or radiosurgery.1-5.

Spinal Ependymomas: An Updated WHO Classification and a Narrative Review.

Ependymomas are neuroepithelial tumors that develop from ependymal cells found in the brain parenchyma and can spread to any part of the spinal cord. Three to six percent of all malignancies affecting the central nervous system (CNS) are ependymomas. Even the most talented surgeons are challenged by spinal cord ependymomas; as a result, research into this clinical phenomenon should continue. Since 1979, the World Health Organization (WHO) has published a classification and grading system for CNS malignancies to ensure consistent diagnostic standards worldwide. The WHO prepared an update on these tumors, paying particular attention to molecular techniques to categorize the therapeutic management of each patient with greater accuracy and clarity. We thoroughly reviewed the literature on the epidemiology, etiology, diagnosis, and treatment of spinal ependymomas since there has not been a recent review of these tumors. This included modifications to the 2021 WHO Classification of Tumors of the Central Nervous System.

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Pituitary Teratoma: A Case Series of Three Cases.

Mature cystic teratoma (MCT) is a benign germ cell tumor, histologically comprising components derived from mesoderm, ectoderm, and endoderm layer tissue. MCT usually has foci of intestinal components and colonic epithelia. Pituitary teratomas containing complete colon features are very rare. Here, we present three cases of sellar teratoma in two men aged 50 and 65 years and a woman aged 30 years. All patients presented with asthenia, adynamia, and loss of strength. A pituitary mass was incidentally observed on magnetic resonance imaging. Histological features showed a mature teratoma formed by gut and colonic epithelium, extended lymphoid tissue with the formation of Peyer's patches, and muscular layer vestiges with a fibrous capsule. The immunohistochemical panel showed reactivity to cytokeratin (CK)7, CKAE6/AE7, carcinoembryonic antigen, octamer-binding transcription factor 4, cluster of differentiation (CD)20, CD3, vimentin, muscle actin, and pituitary tumor-transforming gene 1 in isolated cells. However, alpha-fetoprotein, beta-human chorionic gonadotropin, human placental lactogen, CK20, tumor suppressor protein 53, and Kirsten rat sarcoma were negative. This article describes the clinical and histological features of rare sellar masses as well as survival after therapy.

The role of TNF receptors as mediators of chronic vasculitis in possible milder forms of the CNS tuberculosis.

INTRODUCTION: Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB due to its high mortality and functional sequelae. There are several differential diagnoses for TB; and, it can also cause secondary conditions, such as vasculitis. METHODOLOGY: 155 biopsies, corresponding to 155 different patients out of 5,386 registered biopsies from 2008-2013, met the criteria of unknown etiology vasculitis and evidence of cerebral vascular disease. These were analyzed to assess the presence of central nervous system TB. The selected cases were assessed with Suzaan Marais (SM) criteria for clinical tuberculosis. After that, Ziehl-Neelsen (ZN) staining and polymerase chain reaction (PCR) were performed to amplify a fragment of the insertion sequence IS6110 of M. tuberculosis. 21 patients met the criteria for definitive tuberculosis by ZN staining and PCR, and 2 met the criteria for possible tuberculosis. Tumor necrosis factor (TNF)-α, TNF-R1, and TNF-R2 were determined by immunohistochemistry in histological sections from formalin-fixed paraffin-embedded (FF-PE) tissues in the 23 selected patients. RESULTS: Granulomatous TB was present in almost half of the cases. TNF-R1 and TNF-R2 were expressed mainly in blood vessels, histiocytes, and macrophages. TNF-R2 expression was higher than the other markers, which suggests an anti-inflammatory response against M. tuberculosis. CONCLUSIONS: The histopathological presentation of TB is not always limited to granulomas, abscesses, or meningitis; there are also clinical presentations characterized only with chronic inflammation of nervous and vascular tissue.

Surgical Approach and Further Management of Intracranial Hemangioendothelioma With Double Location: A Case Report.

Hemangioendotheliomas are highly vascularized lesions, and their intracranial presentation is extremely rare. We present the case of a 65-year-old female patient who was evaluated for cranial deformity, headache, and left hemiplegia. Two bone lesions that were destroying and expanding the bone diploe with intracranial extension were identified in the fronto-temporal and parietal regions. Both lesions were multilobed and showed heterogeneous behavior. Mixed hemangioendotheliomas were identified after the successful resection of both tumors in two separate surgical procedures. The prognosis of this type of tumor with an intracranial location is not well-defined because there are too few reported cases.

Teratoma With Malignant Ectomesenchymoma in the Pineal Region: A Case Report.

Tumors involving the pineal gland include germinomas, non-germinomatous, and parenchymal tumors. Sometimes these tumors can be differentiated into rhabdomyosarcoma, which is an aggressive and rapidly recurring sarcoma but is a rare event. We present the case of a 23-year-old male, with an eight-year-long history of a non-treated brain tumor compatible with a teratoma. Chemotherapy and radiotherapy were offered, and two years later, malignant transformation to astrocytoma, rhabdomyosarcoma, neural cell carcinoma, ganglioglioma, and low-grade chondrosarcoma was noted. Immunohistochemistry was valuable in differentiating these entities that confirmed the diagnosis. Malignant transformations may be secondary to the normal transformation of multipotent embryonic cells into more developed tissues after radiotherapy of teratoma and malignant ectomesenchymoma transformation.

Case Report of a Hemangioblastoma With Large Blood Vessels and Rare Vascular Anomalies: Is It Fibromuscular Dysplasia or Arteriovenous Malformation Association?

Hemangioblastoma is considered a benign neoplasm characterized by abnormal vasculature and stromal cells; several pathophysiological mechanisms have been proposed, such as genetic predisposition, hormonal factors, and arterial wall ischemia. Fibromuscular dysplasia is characterized by hyperplasia or thinning of the smooth muscle, elastic fibre destruction, fibrous tissue proliferation, and arterial wall disorganization. We present a cerebellar hemangioblastoma case not associated with Von Hippel Lindau syndrome. Histologically we evidenced big vessels with anomalies of the vascular walls corresponding to fibromuscular dysplasia, and those changes have not been described in these types of tumors. In this light, rare findings could be called vascular malformations or degenerative vascular changes, fibromuscular dysplasia or vascular anomalies. Arterio-venous malformation and hemangioblastoma pathology are rarely presented together. Notwithstanding, we could say that it is a stromal stem cell tumor in a varied stage of differentiation.

Macro Pituitary Adenoma and Frontal Calcified Cavernous Malformation: A Coincidence or a True Partnership?

Collision tumors are rare neoplasms composed of two different types of histological tissues in the same organ. The most frequent association with cerebral cavernous malformations (CCMs) are meningiomas, gliomas, and gangliogliomas, while the most frequent sellar collision is between pituitary adenoma (PA) and craniopharyngiomas, and still very few cases have been reported. We present the case of a 43-year-old woman who started two months ago with a fall from her height followed by severe headache and bilateral hemianopsia. An isointense, enhancing sellar tumor, and a right frontal lesion compatible with CCM were observed on MRI. Surgery was performed through anterior interhemispheric and endoscopic transnasal approaches for the cavernoma and the sellar tumor, respectively, removing both lesions and sending them to pathology. The sellar tumor corresponded to a PA showing positive immunohistochemistry for prolactin and follicle-stimulating hormone (FSH). In the post-op period, the patient developed a seizure and diabetes insipidus, for which she received appropriate treatment. Our findings were conclusive with a collision tumor, since both lesions presented two different histological tissues. Different densities were observed in both lesions using imaging studies, which were later confirmed with histopathology and immunohistochemistry.