Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats : Protection by methionine and aggravation by folates

Nitrous oxide, which inactivates cobalamin when administered to fruit bats, results in severe neurological impairment leading to ataxia, paralysis and death. This occurs after about 6 weeks in animals depleted of cobalamin by dietary restriction, and after about 10 weeks in cobalamin replete bats. Supplementation of the diet with pteroylglutamic acid caused acceleration of the neurological impairment - the first unequivocal demonstration of aggravation of the neurological lesion in cobalamin deficiency by pteroylglutamic acid. The administration of formyltetrahydropteroylglutamic acid produced similar aggravation of the neurological lesion. Supplementation of the diet with methionine protected the bats from neurological impairment, but failed to prevent death. Methionine supplementation protected against the exacerbating effect of folate, preventing the development of neurological changes. These findings lend support to the hypothesis that the neurological lesion in cobalamin deficiency may be related to a deficiency in the methyl donor S-adenosylmethionine which follows diminished synthesis of methionine.     

Building-Associated Neurological Damage Modeled in Human Cells: A Mechanism of Neurotoxic Effects by Exposure to Mycotoxins in the Indoor Environment

Damage to human neurological system cells resulting from exposure to mycotoxins confirms a previously controversial public health threat for occupants of water-damaged buildings. Leading scientific organizations disagree about the ability of inhaled mycotoxins in the indoor environment to cause adverse human health effects. Damage to the neurological system can result from exposure to trichothecene mycotoxins in the indoor environment. This study demonstrates that neurological system cell damage can occur from satratoxin H exposure to neurological cells at exposure levels that can be found in water-damaged buildings contaminated with fungal growth. The constant activation of inflammatory and apoptotic pathways at low levels of exposure in human brain capillary endothelial cells, astrocytes, and neural progenitor cells may amplify devastation to neurological tissues and lead to neurological system cell damage from indirect events triggered by the presence of trichothecenes.     

Retroviruses and nervous system disease.

During the past decade retroviruses have been recognized as causes of human neurological disease. A wide clinical spectrum of neurological and neuromuscular diseases have been reported with HIV infections, and studies of these diseases have raised novel and exciting hypotheses of pathogenesis. As yet the full clinical spectrum of diseases associated with HTLV-1 has yet to be defined, and the pathogenesis of the chronic spastic paraparesis remains a mystery. Chronic neurological diseases in animals caused by both oncoviruses and lentiviruses can provide some clues to the pathogenesis of these newly recognized human neurological illnesses.     

Neurological complications of coronary artery bypass graft surgery: six month follow-up study.

As part of a major prospective study of the neurological complications of coronary artery bypass graft surgery patients were reviewed over six months to determine the clinical course and functional impact of early postoperative complications. One hundred and ninety one out of 312 (61%) patients had developed early postoperative disorders. At six months 165 of the 191 patients with early neurological complications were reviewed. Of the 165, 85 still had detectable neurological signs, but these were often minor and of little functional importance. Only 10 patients had neurological disability at six months, and this was major in only four patients, all of whom had suffered major perioperative stroke. No patient with non-disabling neurological complications in hospital became functionally impaired on returning home. Neurological disorders are not a major cause of failure to return to work by six months after coronary artery bypass surgery. Of 139 patients who were of working age and had not returned to work by six months, only four were prevented by neurological injury related to surgery. The long term prognosis for early neurological disorders after coronary artery bypass surgery is usually favourable, except in those patients who have sustained major perioperative stroke.     

Paraneoplastic cerebellar degeneration as a presentation of breast cancer – a case report and review of the literature

Paraneoplastic cerebellar degeneration is part of a rare spectrum of neurological syndromes whereby gynaecological, lung or breast cancers present primarily with neurological manifestations. The presence of onconeural antibodies and PET scanning help in the challenging diagnosis of these conditions but despite the treatment of the primary cancer, the prognosis for the neurological symptoms is poor.     

A new insight into thymosin β4, a promising therapeutic approach for neurodegenerative disorders

Thymosin β4 (Tβ4), a G-actin-sequestering secreted peptide, improves neurovascular remodeling and central nervous system plasticity, which leads to neurological recovery in many neurological diseases. Inflammatory response adjustment and tissue inflammation consequences from neurological injury are vital for neurological recovery. The innate or nonspecific immune system is made of different components. The Toll-like receptor pro-inflammatory signaling pathway, which is one of these components, regulates tissue injury. The main component of the Toll-like/IL-1 receptor signaling pathway, which is known as IRAK1, can be regulated by miR-146a and regulates NF-κB expression. Due to the significant role of Tβ4 in oligodendrocytes, neurons, and microglial cells in neurological recovery, it is suggested that Tβ4 regulates the Toll-like receptor (TLR) pro-inflammatory signaling pathway by upregulating miR-146a in neurological disorders. However, further investigations on the role of Tβ4 in regulating the expression of miR146a and TLR signaling pathway in the immune response adjustment in neurological disorders provides an insight into mechanisms of action and the possibility of Tβ4 therapeutic effect enhancement.     

人嗜T淋巴细胞Ⅰ型病毒(HTLV-Ⅰ)与神经系统疾病关系的初步研究

1980年,美国的Poiesy和日本的Miyoshi等先后发现人类第一个C型逆转录病毒,后国际上统一命名为人嗜T淋巴细胞Ⅰ型病毒(HTLV-1)。这类病毒以人T_4细胞亚群为靶细胞,并与成人T细胞白血病有病原学关系。1985年,Gessain等报告在热痉挛性瘫痪病人(Tropical Spastic Paraparesis,TSP)血清和脑脊液中查出HTLV-Ⅰ抗体,1986年又在Colombia、Jamaica、Trinidad、Tobago和Ivory Coast等一些国家和地区,也发现某些慢性脊髓神经病变患者(症状相似于TSP病人)的血清和脑脊液中有HTLV-Ⅰ抗体存在。     

Early neurological complications of coronary artery bypass surgery.

A prospective study of 312 patients undergoing elective coronary artery bypass surgery was undertaken to determine the incidence, severity, and functional impact of postoperative neurological complications. Detailed evaluation of the patients showed that neurological complications after surgery were common, occurring in 191 of the 312 patients (61%). Although such a high proportion of the total developed detectable changes, serious neurological morbidity was rare. Neurological disorders resulted in death in only one patient (0.3%) and severe disability in only four (1.3%). Forty eight patients were mildly disabled during the early postoperative period, and the remaining 138 with neurological signs had no serious functional disability. The postoperative neurological disorders detected included one death from cerebral hypoxic damage. Prolonged depression of conscious level was observed in 10 patients (3%) and definite stroke in 15 (5%); 78 (25%) developed ophthalmological abnormalities and 123 (39%) primitive reflexes; postoperative psychosis was observed in four (1%); and 37 (12%) developed disorders of the peripheral nervous system. The incidence of serious neurological problems such as fatal cerebral damage, stroke, and brachial plexopathy is in accordance with experience elsewhere. Lesser abnormalities, whose detection required detailed neurological examination, were much commoner than expected from previous reports.     

Thrombocytosis,circulating platelet aggregates,and neurological dysfunction.

In 12 patients whose neurological dysfunction was associated with thrombocytosis or evidence of abnormal platelet activation, or both, correction of the platelet disorder corresponded with reversal of the neurological symptoms. This suggests that platelet abnormalities may, in certain cases, produce several syndromes of neurological dysfunction, presumably as a result of obstruction of the cerebral microcirculation.     

Proximal Hyperdense Middle Cerebral Artery Sign Predicts Poor Response to Thrombolysis

The aim of our study was to compare the rapid neurological improvement after intravenous recombinant tissue-type plasminogen activator (rtPA) in patients with proximal hyperdense middle cerebral artery sign (p-HMCAS) to those without the sign and those with the distal hyperdense middle cerebral artery sign (d-HMCAS). Admission and 24 hour non-contrast CT scans of 120 patients with middle cerebral artery (MCA) territory stroke who were treated with intravenous rtPA were assessed for the presence of p-HMCAS and d-HMCAS. The sign was classified according to the site of occlusion. Rapid neurological improvement was defined as ≥50% improvement in the NIHSS score at 24 hours after thrombolysis. Rapid neurological recovery after thrombolysis was assessed and compared between the subgroups. Rapid neurological recovery was less common in the pooled group of patients with either p-HMCAS or d-HMCAS than those without the sign (p<0.01). Patients with p-HMCAS were less likely to have rapid neurological recovery than those with d-HMCAS (p<0.01). However, there was no difference in early neurological recovery between patients with d-HMCAS and those without any hyperdense sign. Our study showed that poor neurological recovery post rtPA was confined to p-HMCAS and not to d-HMCAS, indicating that these signs have quite different prognostic significance.     

Relation of Neurological Findings after Cardiac Arrest to Outcome

Routine neurological examination of patients one hour after cardiac arrest seems to be of value in determining the prognosis for life and likelihood of intellectual impairment.In 48 patients 53 episodes of cardiac arrest were followed by serial neurological examinations. Patients were divided into two groups according to neurological findings one hour after cardiac arrest. Patients in group 1 were unresponsive or at most responded in a reflex fashion to painful stimuli at one hour; these patients died or survived with intellectual damage. Patients in group 2 responded purposefully at one hour and survived without neurological damage. These patients commonly showed transient confusional states and a variety of other non-focal abnormalities, and focal signs were seen occasionally.     

Risk of neurological diseases among survivors of electric shocks: a nationwide cohort study, Denmark, 1968-2008

Several studies suggest a link between electric injuries and neurological diseases, where electric shocks may explain elevated risks for neuronal degeneration and, subsequently, neurological diseases. We conducted a retrospective cohort study on the risk of neurological diseases among people in Denmark who had survived an electric accident in 1968-2008. The cohort included 3,133 people and occurrences of neurological diseases were determined by linkage to the nationwide population-based Danish National Register of Patients. The numbers of cases observed at first hospital contact in the cohort were compared with the respective rates of first hospital contacts for neurological diseases in the general population. We observed significantly increased risks for peripheral nerve diseases (standardized hospitalization ratio (SHR), 1.66; 95% confidence interval (CI), 1.22-2.22), for migraine (SHR, 1.80; 95% CI, 1.23-2.54), for vertigo (SHR, 1.60; 95% CI, 1.22-2.05), and for epilepsy (SHR, 1.45; 95% CI, 1.11-1.85). Only small numbers of cases of other neurological diseases were found, making the risk estimates unstable. These findings suggest an association between a single electric shock and increased risks for peripheral nerve diseases, migraines, vertigo, and epilepsy, but confirmation of these observations is needed.     

Neurological disorders in Gulf War veterans

We present a review of neurological function in Gulf War veterans (GWV). Twenty-two studies were reviewed, including large hospitalization and registry studies, large population-based epidemiological studies, investigations of a single military unit, small uncontrolled studies of ill veterans and small controlled studies of veterans. In nearly all studies, neurological function was normal in most GWVs, except for a small proportion who were diagnosed with compression neuropathies (carpal tunnel syndrome or ulnar neuropathy). In the great majority of controlled studies, there were no differences in the rates of neurological abnormalities in GWVs and controls. In a national US study, the incidence of amyotrophic lateral sclerosis (ALS) seems to be significantly increased in GWVs, compared to the rate in controls. However, it is possible that military service, in general, might be associated with an increased risk of ALS, rather than Gulf War service in particular. Taken together, the conclusion is that if a neurological examination in a GWV is within normal limits, then extensive neurological testing is unlikely to diagnose occult neurological disorders.     

The role of autoimmunity to glutamate receptors in neurological disease

Understanding and experimentally approaching the processes that underlie the origin and progression of many severe neurological disorders presents a challenge to both clinical and basic researchers. We have found that the origin of some neurological diseases, including a rare form of childhood epilepsy and a neurodegenerative disease associated with peripheral cancers, may be related to production of physiologically active autoantibodies that are directed towards excitatory ionotropic glutamate receptors of the brain. This suggests that some neurological diseases may result from dysfunction of the immune system.     

肠道病毒71型分子生物学研究进展

肠道病毒7l 型( EV71) 是导致手足口病的主要病原体之一, 常引起多种与神经系统相关的严重疾病。自1969 年首次分离以来, 其感染已在世界范围内引起数次暴发与流行, 尤其是近几年在亚太地区呈上升趋势, 且出现越来越严重的神经系统症状。目前, 对于EV71 病毒结构及其所致严重神经系统症状的机制, 以及疫苗的开发等已进行了大量和深入的研究。     

Evidence that Griscelli syndrome with neurological involvement is caused by mutations in RAB27A,not MYO5A

Griscelli syndrome (GS), a rare autosomal recessive disorder, is characterized by partial albinism, along with immunologic abnormalities or severe neurological impairment or both. Mutations in one of two different genes on chromosome 15q can cause the different subtypes of GS. Most patients with GS display the hemophagocytic syndrome and have mutations in RAB27A, which codes for a small GTPase. Two patients with neurological involvement have mutations in MYO5A, which codes for an actin-based molecular motor. The RAB27A and MYO5A gene products interact with each other and function in vesicle trafficking. We report the molecular basis of GS in a Muslim Arab kindred whose members have extremely variable neurological involvement, along with the hemophagocytic syndrome and immunologic abnormalities. The patients have normal MYO5A genes but exhibit a homozygous 67.5-kb deletion that eliminates RAB27A mRNA and immunocytofluorescence-detectable protein. We also describe the molecular organization of RAB27A and a multiplex polymerase chain reaction assay for the founder deletion in this kindred. Finally, we propose that all patients with GS have RAB27A mutations and immunologic abnormalities that sometimes result in secondary neurological involvement. The two patients described elsewhere who have MYO5A mutations and neurological complications but no immunologic defects may not have GS but instead may have Elejalde syndrome, a condition characterized by mild hypopigmentation and severe, primary neurological abnormalities.     

原发性干燥综合征患者神经系统病变的临床研究

目的：探讨原发性干燥综合征患者合并神经系统损害的发生率,并分析其出现外周和中枢神经系统受累的临床特点。方法：共纳入34例原发性干燥综合征患者,进行神经系统查体,头MRI、脑脊液化验以及电生理检查。结果：34例患者有15例出现神经系统症状,其中11例表现为外周神经受累,分别为3例颅神经受累,6例多发神经病变,1例多发单神经炎,1例怀疑小纤维神经病;4例为中枢神经受累,分别为．1例患者头和脊髓多发脱髓鞘病变,2例大脑单个灶性病变,1例脑干病变。患者间免疫学检查未见显著差异。结论：原发性干燥综合征患者合并神经系统病变的发生率约为44．1％,外周神经损伤尤其是感觉神经损伤更常见,未发现特异性神经系统改变。与不伴神经系统病变的原发性干燥综合征患者相比较,未发现显著的差异以及能够辅助诊断的实验室检查结果。     

Neuroinflammation and COVID-19

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.     

Neurological Complications of Endocarditis in Persons Taking Drugs Intravenously

A study was made of 46 cases of endocarditis in persons known to take drugs intravenously. Findings included significantly lower ages for those patients in whom infections were right-sided. The neurological complication rate was 39 percent overall and 58 percent in the left-sided group. Neurological complications are unusual in right-sided infection. In about a third of those with neurological complications there were sensorial changes without focal signs. Despite a high mortality, neurological complications in Group D streptococcal endocarditis were relatively infrequent. One case is presented in which a foreign body may have contributed to the formation of the embolic material. The clinical and neuropathological features encountered are compared with those reported in persons with endocarditis who were not addicts. The review indicates that neurological complications in nonaddicts and in addicts are similar in type but are more common and severe in addicts.