Acute Central Nervous System Disorders Research Articles

Post Covid Auto Immune Mediated Encephalopathy by Caspr2 Auto Antibody: The Report of Neurological Division o f “Carlo Poma Civil” Hospital of Mantua

A recent cross sectional study ( Liu, 2021 ) suggests that SARS CoV 2 infection has a potential long term impact on the cognition of patients: we have to face with post covid syndrome and with long covid syndrome, the first characterized by symptoms in regression after an year by infection, the last with persisting symptoms after an year by infection. As the COVID 19 pandemic is still raging in many countries and is expected to last for a long period, the long term cognitive sequelae may bec ome a major publi c health issue long after the pandemic has ended. Longitudinal studies to follow up patients who have recovered from COVID 19 are necessary for better understanding the long term cognitive consequences of COVID 19, particularly among those who have recovered from severe disease. But these are not the unique problems of the so called NEUROCOVID. Neuromuscular manifestations of new coronavirus disease 2019 (COVID‐19) infection are frequent, and include dizziness, headache, myopathy, severe (also axonal) Gui llain Barrè Syndrome and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate ( Shimohata, 2022 An other severe condition is rappresented by autoimmune encefalopathies COVID related. The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS‐CoV‐2 v irus, encephalopa thy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune‐mediated encephalitis that occurs after infection.

Особенности биоэлектрической активности ретросплениальной коры головного мозга

Human brain is one of the most difficult organs to study. The possibility of developing the technologies that have sufficient scientific accuracy and economic accessibility and never violate the moral and ethical standards of human society is of great interest. The study was aimed to study the possibility of assessing the retrosplenial cortex (RSC) structures’ activity based on the EEG analysis of brain activity in the alpha frequency range in 36 healthy volunteers with an average age of 29.1 years, no acute central nervous system disorders or exacerbation of chronic central nervous system disorders, severe traumatic brain injuries, mental disorders or epilepsy. Significant source localizations were obtained by solving the EEG inverse problem that could be used for identification of the cerebral retrosplenial cortex structures’ bioelectric activity. The use of such technology will allow us to expand the scope of the research focused on assessing the brain functional activity in both research and clinical centers, thereby paving the way for understanding the features of the brain structures’ activity in physiologically normal conditions and in individuals with mental disorders caused by various functional alterations in the brain.

Neuro-COVID-19.

Neuromuscular manifestations of new coronavirus disease 2019 (COVID‐19) infection are frequent, and include dizziness, headache, myopathy, and olfactory and gustatory disturbances. Patients with acute central nervous system disorders, such as delirium, impaired consciousness, stroke and convulsive seizures, have a high mortality rate. The encephalitis/encephalopathy that causes consciousness disturbance and seizures can be classified into three conditions, including direct infection with the SARS‐CoV‐2 virus, encephalopathy caused by central nervous system damage secondary to systemic hypercytokinemia (cytokine storm) and autoimmune‐mediated encephalitis that occurs after infection. The sequelae, called post‐acute COVID‐19 syndrome or long COVID, include neuromuscular manifestations, such as anxiety, depression, sleep disturbance, muscle weakness, brain fog and cognitive impairment. It is desirable to establish diagnostic criteria and treatment for these symptoms. Vaccine‐induced thrombotic thrombocytopenia, Guillain–Barré syndrome, bilateral facial paralysis, encephalitis and opsoclonus‐myoclonus syndrome have been reported as adverse reactions after the COVID‐19 vaccine, although these are rare.

Changes in plasma lipoxin A4, resolvins and CD59 levels after ischemic and traumatic brain injuries in rats

Ischemic and traumatic brain injuries are the major acute central nervous system disorders that need to be adequately diagnosed and treated. To find biomarkers for these acute brain injuries, plasma levels of some specialized pro-resolving mediators (SPMs, i.e., lipoxin A4 [LXA4], resolvin [Rv] E1, RvE2, RvD1 and RvD2), CD59 and interleukin (IL)-6 were measured at 0, 6, 24, 72, and 168 h after global cerebral ischemic (GCI) and traumatic brain injuries (TBI) in rats. Plasma LXA4 levels tended to increase at 24 and 72 h after GCI. Plasma RvE1, RvE2, RvD1, and RvD2 levels showed a biphasic response to GCI; a significant decrease at 6 h with a return to the levels of the sham group at 24 h, and again a decrease at 72 h. Plasma CD59 levels increased at 6 and 24 h post-GCI, and returned to basal levels at 72 h post-GCI. For TBI, plasma LXA4 levels tended to decrease, while RvE1, RvE2, RvD1, and RvD2 showed barely significant changes. Plasma IL-6 levels were significantly increased after GCI and TBI, but with different time courses. These results show that plasma LXA4, RvE1, RvE2, RvD1, RvD2, and CD59 levels display differential responses to GCI and TBI, and need to be evaluated for their usefulness as biomarkers.

Blood-Brain Barrier: From Physiology to Disease and Back.

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At the same time, the BBB regulates transport of molecules into and out of the central nervous system (CNS), which maintains tightly controlled chemical composition of the neuronal milieu that is required for proper neuronal functioning. In this review, we first examine molecular and cellular mechanisms underlying the establishment of the BBB. Then, we focus on BBB transport physiology, endothelial and pericyte transporters, and perivascular and paravascular transport. Next, we discuss rare human monogenic neurological disorders with the primary genetic defect in BBB-associated cells demonstrating the link between BBB breakdown and neurodegeneration. Then, we review the effects of genes underlying inheritance and/or increased susceptibility for Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and amyotrophic lateral sclerosis (ALS) on BBB in relation to other pathologies and neurological deficits. We next examine how BBB dysfunction relates to neurological deficits and other pathologies in the majority of sporadic AD, PD, and ALS cases, multiple sclerosis, other neurodegenerative disorders, and acute CNS disorders such as stroke, traumatic brain injury, spinal cord injury, and epilepsy. Lastly, we discuss BBB-based therapeutic opportunities. We conclude with lessons learned and future directions, with emphasis on technological advances to investigate the BBB functions in the living human brain, and at the molecular and cellular level, and address key unanswered questions.

Cardiac disease in brain-heart disorders.

Abstract There are a number of acute central nervous system (CNS) disorders, which trigger an acute cardiac reaction (brain-heart disorders). Both the brain and the heart may be previously normal or affected by chronic hereditary or acquired disease. The most common of these acute CNS disorders include subarachanoid bleeding, epilepsy, ischaemic stroke, intracerebral bleeding, infectious meningitis/encephalitis, immune-encephalitis, posterior reversible encephalopathy syndrome, migraine, central sleep apnoea syndrome, restless leg syndrome, and traumatic brain injury. Affection of the heart caused by these CNS abnormalities includes takotsubo syndrome, arrhythmias, heart failure or systolic/diastolic dysfunction, myocardial infarction, arterial hypertension, or pulmonary hypertension of which takotsubo syndrome, arrhythmias, or heart failure are the most frequent. Arrhythmias triggered by acute CNS disease include supraventricular or ventricular arrhythmias, including sudden cardiac death. Cardiologists a...

Therapeutic plasma exchange in children with acute autoimmune central nervous system disorders.

There is a growing evidence for autoimmunity in acute central nervous system (CNS) disorders and treatment with therapeutic plasma exchange (TPE) may be considered. The aim was to share our experience on the clinical application of TPE in these disorders and to present a reproducible protocol which can be used even in small children. We present a series of 8 children aged 2-12 years with transverse myelitis, Bickerstaff's brainstem encephalitis, neuromyelitis optica, and acute paraneoplastic or unspecified encephalitis in whom TPE was used as a second-line or rescue treatment. A total of 104 TPE sessions were performed where 80-110 ml/kg of plasma was exchanged using 4% albumin solution and fresh frozen plasma. Six episodes of TPE-related adverse events were documented. Fibrinogen concentrations decreased after the first TPE, whereas platelets decreased gradually. One patient died in the course of the acute illness. Three children achieved a complete resolution of symptoms, 2 children have mild sequelae; whereas 2 children remain paraplegic after a follow-up of 3 to 17 months. We report 8 children with presumably autoimmune-mediated, acute CNS disorders treated with TPE as a rescue therapy. Although the effect of TPE can only be inferred, 5 children had a good clinical outcome. TPE is feasible even in small children with acute autoimmune CNS disorders.

CSWS Versus SIADH as the Probable Causes of Hyponatremia in Children With Acute CNS Disorders.

There is a major problem about the incidence, diagnosis, and differentiation of cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with acute central nervous system (CNS) disorders. According to rare reports of these cases, this study was performed in children with acute CNS disorders for diagnosis of CSWS versus SIADH. This prospective study was done on children with acute CNS disorders. The definition of CSWS was hyponatremia (serum sodium ≤130 mEq/L), urine volume output ≥3 ml/kg/hr, urine specific gravity ≥1020 and urinary sodium concentration ≥100 mEq/L. Also, patients with hyponatremia (serum sodium ≤130 mEq/L), urine output < 3 ml/kg/hr, urine specific gravity ≥1020, and urinary sodium concentration >20 mEq/L were considered to have SIADH. Out of 102 patients with acute CNS disorders, 62 (60.8%) children were male with mean age of 60.47±42.39 months. Among nine children with hyponatremia (serum sodium ≥130 mEq/L), 4 children had CSWS and 3 patients had SIADH. In 2 cases, the cause of hyponatremia was not determined. The mean day of hyponatremia after admission was 5.11±3.31 days. It was 5.25±2.75 and 5.66±7.23 days in children with CSWS and SIADH, respectively. Also, the urine sodium (mEq/L) was 190.5±73.3 and 58.7±43.8 in patients with CSWS and SIADH, respectively. According to the results of this study, the incidence of CSWS was more than SIADH in children with acute CNS disorders. So, more attention is needed to differentiate CSWS versus SIADH in order to their different management.

Masquerades of Acquired Demyelination in Children

The diagnosis of acquired demyelinating syndromes of the central nervous system in children requires exclusion of other acute central nervous system disorders. In a 23-site national demyelinating disease study, standardized clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained prospectively from onset, and serially at 3, 6, and 12 months and annually. Twenty of 332 (6%) participants (mean [SD] age, 10.21 [4.32] years; 12 (60%) female) were ultimately diagnosed with vascular disorders (primary or secondary central nervous system vasculitis, vasculopathy, stroke, or migraine, n = 11 children), central nervous system malignancy (n = 3), mitochondrial disease (n = 2), or central nervous system symptoms in the accompaniment of confirmed infection (n = 4). Red flags that may serve to distinguish disorders in the differential of acquired demyelination are described.

Microglial physiopathology: how to explain the dual role of microglia after acute neural disorders?

Microglia are the resident macrophages of the central nervous system (CNS). In physiological conditions, resting microglia maintain tissue integrity by scanning the entire CNS parenchyma through stochastic and complex movements of their long processes to identify minor tissue alterations. In pathological conditions, over-activated microglia contribute to neuronal damage by releasing harmful substances, including inflammatory cytokines, reactive oxygen species, and proteinases, but they can provide tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. The reasons for this apparent paradox are unknown. In this paper, we first review the physiological role as well as both detrimental and beneficial actions of microglial during acute CNS disorders. Further, we discuss the possible reasons for this microglial dual role following CNS insults, considering that the final microglial phenotype is a direct consequence of both noxious and beneficial stimuli released into the extracellular space during the pathological insult. The nature of these micro-glial ligands is unknown, but we hypothesize that harmful and beneficial stimuli may be preferentially located at specific anatomical niches along the pathological environment triggering both beneficial and deleterious actions of these glial cells. According to this notion, there are no natural populations of detrimental microglia, but is the pathological environment that determines the final microglial phenotype.

Factors Influencing Receipt of Outpatient Rehabilitation Services Among Veterans Following Lower Extremity Amputation

Zhou J, Bates BE, Kurichi JE, Kwong PL, Xie D, Stineman MG. Factors influencing receipt of outpatient rehabilitation services among veterans following lower extremity amputation. Objective To determine patient-, treatment-, and facility-level characteristics associated with receiving outpatient rehabilitation services after lower extremity amputation within the Veterans Affairs (VA) system. Design Observational study. Setting All Veterans Affairs Medical Centers (VAMCs). Participants Veterans (N=4165) with lower extremity amputation discharged from VAMCs between October 1, 2002, and September 20, 2004. Interventions Not applicable. Main Outcome Measures Receipt of outpatient rehabilitation services up to 1 year postdischarge. A Cox proportional hazards model was used to determine the adjusted hazard ratio and 95% confidence interval of veterans to receive outpatient services. Results Sixty-five percent of veterans with lower extremity amputation received outpatient services. Older veterans, patients admitted for surgical amputation from extended care rather than transferred from another hospital, and those with transfemoral and/or bilateral rather than unilateral transtibial amputations were less likely to receive outpatient services. Those with serious comorbidities and those who had procedures for acute central nervous system disorders, active cardiac pathology, serious nutritional compromise, and severe renal disease during the surgical hospitalization less often initiated outpatient care. Patients who received inpatient consultative rehabilitation compared with inpatient specialized rehabilitation, and who were treated in the Northeast compared with the Southeast less often initiated outpatient care. Finally, those discharged to home or other locations rather than extended care had an initial increased likelihood of receiving outpatient service, but by 180 days postdischarge those discharged to extended care were more likely to initiate outpatient services. Conclusions Both clinical characteristics and types of rehabilitation services received appear to influence the receipt of outpatient rehabilitation services. Geographic location also affected the receipt of outpatient rehabilitation, suggesting that care patterns are not standardized across the nation.

Clinical Factors Associated with Prescription of a Prosthetic Limb in Elderly Veterans

To determine how advanced age influences prosthetic prescription. Retrospective cohort analysis with theory-driven logistic regression models. A Post Amputation Quality-of-Life (PAQ) framework of outcomes was proposed and empirically tested. Veterans Affairs Medical Centers. Two thousand three hundred seventy-five veterans with lower extremity amputations discharged between October 1, 2002, and September 30, 2003. Prosthetic prescription within 1 year of amputation. Patients younger than 76 were 4.5 times as likely to receive a prescription compared to those aged 86 and older (odds ratio=4.51, 95% confidence interval=1.36-14.99) after controlling for sex, marital status, living circumstance before hospitalization, anatomical level, etiologies, comorbidities, medical acuity, and initial functional status. Patients admitted from extended care and patients with peripheral vascular disease, systemic sepsis, renal failure, congestive heart failure, psychoses, metastatic cancer, paralysis, or other neurological disorders were less likely to receive a prescription, as were patients who underwent procedures for acute central nervous system disorders, severe renal disease, or serious nutritional compromise. Veterans evaluated initially as more cognitively and physically able had higher likelihood of prosthetic prescription, and those with transtibial amputations had higher likelihood of prosthetic prescription than those with transfemoral amputations. Amputees aged 75 and older are less likely to receive a prosthetic limb prescription than younger individuals, even after controlling for comorbidities and functional status. Findings support the PAQ framework, in which contexts, etiologies, anatomic level, comorbidities, medical acuity, and initial function are determinants of outcome. Medical and functional conditions that adversely affect level of energy, ability to move independently, or ability to exercise judgment reduce the likelihood of prosthetic prescription.

Ischemia-Induced Interleukin-6 as a Potential Endogenous Neuroprotective Cytokine against NMDA Receptor-Mediated Excitoxicity in the Brain

In the brain, the expression of the pleiotropic cytokine interleukin-6 (IL-6) is enhanced in various chronic or acute central nervous system disorders. However, the significance of IL-6 production in such neuropathologic states remains controversial. The present study investigated the role of IL-6 after cerebral ischemia. First, the authors showed that focal cerebral ischemia in rats early up-regulated the expression of IL-6 mRNA, without affecting the transcription of its receptors (IL-6Ralpha and gp130). Similarly, the striatal injection of N-methyl-D-aspartate (NMDA) in rats, a paradigm of excitotoxic injury, activated the expression of IL-6 mRNA. The involvement of glutamatergic receptor activation was further investigated by incubating cortical neurons with NMDA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). NMDA and ionomycin (a calcium ionophore) up-regulated IL-6 mRNA, suggesting that neurons may produce IL-6 in response to the calcium influx mediated through NMDA receptors. The potential role of IL-6 during ischemic/excitotoxic insults was then studied by testing the effect of IL-6 against apoptotic or excitotoxic challenges in cortical cultures. IL-6 did not prevent serum deprivation- or staurosporine-induced apoptotic neuronal death, or AMPA/kainate-mediated excitotoxicity. However, in both mixed and pure neuronal cultures, IL-6 dose-dependently protected neurons against NMDA toxicity. This effect was blocked by a competitive inhibitor of IL-6. Overall, the results suggest that the up-regulation of IL-6 induced by cerebral ischemia could represent an endogenous neuroprotective mechanism against NMDA receptor-mediated injury.