A 54-year-old man complained of episodic stinging in his left eye along with weakness and numbness in his right upper and lower extremities for 1 month. The neurological examination was negative. MRI showed bilateral paraventricular demyelination. CTA showed significant stenosis of the left internal carotid (60%) and vertebral arteries (70%). He underwent left internal carotid stenting and was intubated during the procedure. After the procedure, he did not wake up from anesthesia, and he developed flexion and spasticity in the right arm immediately. Thereafter, he was sent to the neurocritical unit (NCU). Anti-seizure treatment was adopted due to recurrent general tonic-clonic seizures. Two days later (day 15 of hospitalization), brain edema and meningitis appeared in MRI, and contrast-induced encephalopathy (CIE) was mainly considered, with the support of CSF results. After 18 days (day 21 of hospitalization), serum anti-neurexin-3α IgG was detected at a dilution of 1:10. Anti-neurexin-3α-associated encephalitis was diagnosed. The patient was fully recovered 7 months after taking immunoglobulin, steroids, mortimycophenate, and cyclophosphamide. Meanwhile, anti-neurexin-3α antibody IgG was negative in both CSF and serum. MRI was also normal. Although scarce evidence clarified the relationship between CIE and anti-neurexin-3α-associated encephalitis, we inferred that the BBB damaged by CIE may result in the anti-neurexin-3α antibody entrance into the CSF from serum, which led to autoimmune encephalitis (AIE).

Posterior reversible encephalopathy syndrome (PRES) is a neurovascular sequence noted in patients with preeclampsia/eclampsia, solid-organ/bone marrow transplantation, and malignant hypertension. The mechanism in which PRES occurs has not yet been determined. It has been hypothesized that it may be related to endothelial cell dysfunction or injury leading to the compromise of the blood-brain barrier. The clinical presentations vary but are similar to symptoms of increased intracranial pressure, such as headache, visual changes, focal neurological deficits, seizures, and altered mental status. Although the pathology suggests reversibility, that is not always the case in which severe ischemic damage has occurred. We present a patient who came to the emergency room with a history of substance abuse and tested positive on a urinary toxicology screen for methamphetamine and cocaine. In the US, polysubstance use has been more prevalent in recent years. Furthermore, literature has highlighted the additive effects on one\'s blood pressure when such drugs are combined. Our patient presented with altered mental status, hypertension, and pinpoint pupils. Over the course of her stay, the patient\'s mentation slowly improved and was able to follow commands intermittently. We believe that this is the first documented case of polysubstance abuse in correlation to PRES. We hypothesize that the mechanism of PRES resulted from the multiplicative effect of several illicit drugs known to cause transient hypertensive episodes and their ability to disrupt the structural proteins imperative for the blood-brain barrier.

Although myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has a specific and distinctive profile of clinical features, the disease remains an enigma because causal explanation of the pathobiological matrix is lacking. Several potential disease mechanisms have been identified, including immune abnormalities, inflammatory activation, mitochondrial alterations, endothelial and muscular disturbances, cardiovascular anomalies, and dysfunction of the peripheral and central nervous systems. Yet, it remains unclear whether and how these pathways may be related and orchestrated. Here we explore the hypothesis that a common denominator of the pathobiological processes in ME/CFS may be central nervous system dysfunction due to impaired or pathologically reactive neuroglia (astrocytes, microglia and oligodendrocytes). We will test this hypothesis by reviewing, in reference to the current literature, the two most salient and widely accepted features of ME/CFS, and by investigating how these might be linked to dysfunctional neuroglia. From this review we conclude that the multifaceted pathobiology of ME/CFS may be attributable in a unifying manner to neuroglial dysfunction. Because the two key features - post exertional malaise and decreased cerebral blood flow - are also recognized in a subset of patients with post-acute sequelae COVID, we suggest that our findings may also be pertinent to this entity.

Imaging limitations, invasive tissue biopsies and poor information over the course of treatment to evaluate \'real-time\' tumor dynamics justify the emerging use of liquid biopsies in the field of brain tumors. Circulating tumor cells (CTCs) from high-grade astrocytomas might reach the circulation by crossing the blood-brain barrier. Here, for the first time, CTCs cytology in a case of pylocitic astrocytoma is described. An obstructive hydrocephalous due to a lateral mesencephalic tectum mass occluding the Silvio Aqueduct was diagnosed in a young, 18 years old, male. Considering the location of the tumor and the rapid deterioration of the neurological status, it has been decided to urgency treat the patient with ventriculoperitoneal shunting. Magnetic resonance imaging showed a nodular shaped lesion localized within the left lateral mesencephalic tectum. Stereotactic biopsy was not approachable due significant risk of neurological consequences. The diagnosis was performed by blood sampling, a non-invasive procedure for the patient, in order to provide tumor information. Cytopathological features on detected circulating atypical GFAP positive cells led to pilocytic diagnosis confirmed by the patient\'s 68 months outcome.

Pembrolizumab, an immune-checkpoint inhibitor (ICI), is a humanized monoclonal antibody that binds to programmed cell death-1 receptor (PD-1) and thereby inhibits binding to its ligand, which inhibits the suppression of activated T cells by cancer cells, resulting in enhancing antitumour immunity. Although several cases of encephalitis have been reported as immune-related adverse effects of ICIs, epilepsy has not been reported following ICI treatment. We describe the case of an elderly woman with bladder carcinoma who experienced two episodes of generalized seizures after treatment with pembrolizumab. The episodes were atypical of encephalitis, because the seizures were completely responsive to AEDs and the CSF parameters normalized completely without immunotherapy. Since interictal EEG revealed persistent epileptic discharges after the seizures, pembrolizumab was considered to have induced a chronic state of epileptogenicity as the possible pathology, with a clinical picture similar to that of autoimmune epilepsy. The possibility that ICIs may cause an immune-related adverse effect, such as a chronic epileptic condition, should be considered, since ICIs are used widely.

BACKGROUND: Occurrence of basal ganglia involvement in neuromyelitis optica spectrum disorders (NMOSD) has rarely been reported and none documented pathologically.
METHODS: A 73-year-old female was clinically diagnosed with a NMOSD based on the clinical and radiological features and positive serum autoantibodies to AQP4. One month before her death, she became acutely ill with disturbed consciousness and right hemiparesis, and was diagnosed and treated as having basal ganglia infarction based on the brain CT. She made a partial recovery but later died from heart failure. At autopsy, the corresponding basal ganglia process revealed a large fresh area of necrosis. Histologically, several pathological signatures of NMOSD could be recognized in the lesion, including inflammatory cell infiltrations by B and T lymphocytes, perivascular complement and fibrinogen deposition, and the appearance of numerous phagocytosed corpora amylacea within the infiltrating macrophages.
CONCLUSIONS: The present case illustrates that basal ganglia may be directly involved in the pathological processes of NMOSD, although the possibility of modification of the lesions by superimposed regional ischemia could not be excluded.

Hyperbaric oxygen exposure is a recent hazzard for higher animals that originated as humans began underwater construction, exploration, and sports. Exposure can lead to abnormal brain EEG, convulsions, and death, the time to onset of each stage of pathology decreasing with increase in oxygen pressure. We provide evidence that hyperoxia, through oxidative phosphorylation, increases the energy state ([ATP]/[ADP][Pi]) of cells critical to providing glucose to cells behind the blood brain barrier (BBB). Brain cells without an absolute dependence on glucose metabolism; i.e. those having sufficient ATP synthesis using lactate and glutamate as oxidizable substrates, are not themselves very adversely affected by hyperoxia. The increased energy state and decrease in free [AMP], however, suppress glucose transport through the blood brain barrier (BBB) and into cells behind the BBB. Glucose has to pass in sequence through three steps of transport by facilitated diffusion and transporter activity for each step is regulated in part by AMP dependent protein kinase. The physiological role of this regulation is to increase glucose transport in response to hypoxia and/or systemic hypoglycemia. Hyperoxia, however, through unphysiological decrease in free [AMP] suppresses 1) glucose transport through the BBB (endothelial GLUT1 transporters) into cerebrospinal fluid (CSF); 2) glucose transport from CSF into cells behind the BBB (GLUT3 transporters) and (GLUT4 transporters). Cumulative suppression of glucose transport results in local regions of hypoglycemia and induces hypoglycemic failure. It is suggested that failure is initiated at axons and synapses with insufficient mitochondria to meet their energy requirements.

Tumor necrosis factor-α (TNFα) plays a major role in inflammatory and vascular processes after cerebral ischemia. TNFa-Inhibitors have, on the one hand, been associated with thromboembolic events; on the other hand, they may prevent brain edema after stroke or injury. Here, we report on a 38-year old Caucasian male with a history of Crohn´s disease, treated with adalimumab, who presented without brain edema and only minor sequelae after a major ischemic stroke. This case report illustrates two interesting aspects: 1) the treatment with adalimumab could, in that case, be the etiology for the thromboembolic event; and (2) pretreatment with this TNFa-Inhibitor was the most likely reason why the formation of brain edema was suppressed.

Microphysiological systems (MPS) may be able to provide the pharmaceutical industry models that can reflect human physiological responses to improve drug discovery and translational outcomes. With lack of efficacy being the primary cause for drug attrition, developing MPS disease models would help researchers identify novel targets, study mechanisms in more physiologically-relevant depth, screen for novel biomarkers and test/optimize various therapeutics (small molecules, nanoparticles and biologics). Furthermore, with advances in inducible pluripotent stem cell technology (iPSC), pharmaceutical companies can access cells from patients to help recreate specific disease phenotypes in MPS platforms. Combining iPSC and MPS technologies will contribute to our understanding of the complexities of neurodegenerative diseases and of the blood brain barrier (BBB) leading to development of enhanced therapeutics.

The success of nanomedicine as a new strategy for drug delivery and targeting prompted the interest in developing approaches toward basic and clinical neuroscience. Despite enormous advances on brain research, central nervous system (CNS) disorders remain the world\'s leading cause of disability, in part due to the inability of the majority of drugs to reach the brain parenchyma. Many attempts to use nanomedicines as CNS drug delivery systems (DDS) were made; among the various non-invasive approaches, nanoparticulate carriers and, particularly, polymeric nanoparticles (NPs) seem to be the most interesting strategies. In particular, the ability of poly-lactide-co-glycolide NPs (PLGA-NPs) specifically engineered with a glycopeptide (g7), conferring to NPs\' ability to cross the blood brain barrier (BBB) in rodents at a concentration of up to 10% of the injected dose, was demonstrated in previous studies using different routes of administrations. Most of the evidence on NP uptake mechanisms reported in the literature about intracellular pathways and processes of cell entry is based on in vitro studies. Therefore, beside the particular attention devoted to increasing the knowledge of the rate of in vivo BBB crossing of nanocarriers, the subsequent exocytosis in the brain compartments, their fate and trafficking in the brain surely represent major topics in this field.