Prediction of affective psychoses response to lithium prophylaxis. The role of socio-demographic, clinical, psychological and biological variables

A set of socio-demographic, clinical, psychological and biological variables was examined in 100 patients diagnosed according to Perris as bipolar affective psychotics or unipolar depressive psychotics, maintained on prophylactic lithium for 2 years and divided into responders and non-responders to this treatment on the basis of strict criteria. The results confirmed the potential role of four indices as predictors of response to prophylaxis: a positive family history of bipolar affective illness and a high red blood cell/plasma lithium ratio (positive predictors) and the presence of the HLA-A3 antigen and a high score on the Neuroticism Scale of the Eysenck Personality Questionnaire (negative predictors). A stepwise discriminant analysis showed that neuroticism score, lithium ratio and HLA-A3 antigen, taken together, correctly classified 74.6% of responders and 68.3% of non-responders. It is hypothesized that these variables as a group may be of practical value in predicting response to lithium prophylaxis, and that pharmacogenetic and, perhaps, personality factors may be involved in treatment failures.     

Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system

Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li⁺ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K⁺-distribution of neurons and glial cells. In view of the therapeutic action of Li⁺ in manicdepressive disease, a special effort was made to determine the threshold concentration for the actions of Li⁺ on the parameters described above. It was observed that Li⁺ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li⁺ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li⁺ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li⁺ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li⁺ may be an interaction with the transport-function of the Na⁺/K⁺ pump.     

手足口病患儿合并中枢神经系统损害临床分析

目的：探讨手足口病患儿合并中枢神经系统损害的临床特点及治疗方法。方法选取合并中枢神经系统损害的手足口病患儿137例,随机分为2组。回顾分析所有患者的临床特点、试验时间、检查结果,并进行统计。2组患儿均实施综合治疗,在此基础上,对照组给予胞二磷胆碱静滴,观察组给予神经节苷脂静滴。对2组患儿神经系统好转时间、发热缓解时间及痊愈时间进行统计。于治疗10 d时测定2组患儿神经元特异性烯醇化酶水平,评价2组患儿治疗效果。结果发热、皮疹、易惊是手足口病患儿合并中枢神经系统损害最为常见的临床表现;脑脊液细胞数升高是实验室检查中最常见的异常。观察组患者神经系统好转时间、发热缓解时间、痊愈时间及神经元特异性烯醇化酶水平均明显低于对照组。结论手足口病患儿合并中枢神经系统损害的临床表现缺乏特异性,治疗时应在综合治疗的基础上加用神经节苷脂静脉注射。     

神经节苷脂治疗小儿手足口病并中枢神经系统损害的疗效观察

目的观察神经节苷脂治疗小儿手足口病并中枢神经系统损害的临床疗效。方法 85例患儿随机分为治疗组与对照组,对照组采用常规治疗加胞二磷胆碱注射液静滴,治疗组在对照组基础上加单唾液酸四己糖神经节苷脂注射液静滴,均治疗7d。根据患儿精神症状、体温、皮疹、血常规检查及脑电图恢复情况进行疗效评定,详细记录2组主要症状消失时间、病程及住院时间、神经元特异性烯醇化酶(NSE)水平。结果治疗组总有效率83.72%,对照组为64.28%,差异有统计学意义(Z=1.981,P0.05);治疗后治疗组NSE水平(19.78±4.25)μg/L,对照组为(28.45±4.17)μg/L,差异有统计学意义(t=9.491,P0.05);治疗组脑电图恢复正常率60.47%,明显高于对照组的38.00%(χ2=4.253,P=0.032);治疗组发热、惊跳、肢体抖动消失时间、病程及住院时间均较对照组明显缩短,差异有统计学意义(P0.05)。结论小儿手足口病并中枢神经系统损害给予神经节苷脂治疗,可明显改善或消除患儿神经系统症状,提高疗效,缩短病程。     

主动脉夹层并发神经系统损害的临床和影像学特征

目的探讨主动脉夹层并发神经系统损害的临床和影像学特征。方法回顾性分析14例主动脉夹层并发神经系统病变患者的临床资料。结果本组患者中>40岁中老年人13例(92.9%),均为急性起病,有高血压病史9例,发病时血压升高9例、降低3例、测不到2例;临床表现:剧烈胸痛5例,胸背痛4例,腹痛、腰痛伴呕吐2例,休克2例;神经系统表现:眩晕5例,意识障碍4例,偏瘫2例,言语不清1例,截瘫2例,感觉减退3例(1例偏身,2例胸4、胸6平面以下)。14例胸腹部CT CTA均显示主动脉真假腔,并清晰见内膜裂口位置(DebakeysⅠ型2例,Ⅱ型7例,Ⅲ型5例)及附壁血栓,其中8例胸腹部MRI可见明显的真假腔,真腔呈流空信号,假腔T1及T2WI均呈高信号。结论主动脉夹层并发神经系统损害的主要临床表现为脑和脊髓缺血性损害的症状及体征。CT和MRI可显示主动脉夹层的假腔及血管内膜破裂口。     

Acute and long-term effects of trophic exposure to silver nanospheres in the central nervous system of a neotropical fish Hoplias intermedius

Nanotechnologies are at the center of societal interest, due to their broad spectrum of application in different industrial products. The current concern about nanomaterials (NMs) is the potential risks they carry for human health and the environment. Considering that NMs can reach bodies of water, there is a need for studying the toxic effects of NMs on aquatic organisms. Among the NMs’ toxic effects on fish, the interactions between NMs and the nervous system are yet to be understood. For this reason, our goal was to assess the neurotoxicity of polyvinylpyrrolidone coated silver nanospheres [AgNS (PVP coated)] and compare their effects in relation to silver ions (Ag⁺) in carnivorous Hoplias intermedius fish after acute and subchronic trophic exposure through the analysis of morphological (retina), biochemical (brain) and genetic biomarkers (brain and blood). For morphological biomarkers, damage by AgNS (PVP coated) in retina was found, including morphological changes in rods, cones, hemorrhage and epithelium rupture, and also deposition of AgNS (PVP coated) in retina and sclera. In the brain biomarkers, AgNS (PVP coated) did not disturb acetylcholinesterase activity. However, lowered migration of the DNA tail in the Comet Assay of blood and brain cells was observed for all doses of AgNS (PVP coated), for both acute and subchronic bioassays, and in a dose-dependent manner in acute exposure. Ag⁺ also reduced the level of DNA damage only under subchronic conditions in the brain cells. In general, the results demonstrated that AgNS (PVP coated) do not cause similar effects in relation to Ag⁺. Moreover, the lowered level of DNA damage detected by Comet Assay suggests that AgNS (PVP coated) directly interacts with DNA of brain and blood cells, inducing DNA-DNA or DNA-protein crosslinks. Therefore, the AgNS (PVP coated) accumulating, particularly in the retina, can lead to a competitive disadvantage for fish, compromising their survival.     

Clinical and neuropathological features of a neurodegenerative disorder in the central nervous system with progressive head drooping (Kubisagari)

The clinical and neuropathological features of a case of a neurodegenerative disorder with pronounced and progressive head drooping, in Japanese Kubisagari, are reported. This female patient died at the age of 72 years after an approximately 20-year history of peculiar posture with progressive head drooping (Kubisagari) and lordosis (bowed posture), parkinsonism, dysphonia and slight muscle wasting of the face, tongue, neck, and distal portions of the upper extremities. She did not display mental deterioration until the terminal stage of the illness. A simple macroscopic inspection of formalin-fixed sections of the central nervous system (CNS) showed prominent atrophic frontal and temporal lobes, brownish discoloration of the putamen and an atrophic pyramidal tract. Light microscopy revealed severe neuron loss with fibrillary gliosis at both the above-mentioned lobes and the putamen. Both the facial and hypoglossal nuclei had almost disappeared. Motor neurons in the spinal cord were moderately to markedly decreased. Neither Bunina nor Lewy bodies, senile plaque, nor Pick's argyrophilic neuronal inclusions were observed, but very occasionally ubiquitin-positive neurons were found in the temporal cortex. In conclusion, the hitherto-unrecognized neuropathological findings in the CNS corresponding to progressive head drooping (Kubisagari) suggest that this is a neurodegenerative disorder of the CNS, possibly an atypical form of amyotrophic lateral sclerosis.     

The role of matrix metalloproteinases in autoimmune damage to the central and peripheral nervous system

Members of the family of matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of inflammatory demyelination. MMPs apparently mediate important steps in the genesis of inflammatory demyelination, such as cell migration, blood-brain/nerve barrier breakdown, demyelination, and cytokine activation. This review will highlight in vitro as well as in vivo findings, which support the importance of this group of proteases in the pathogenesis of inflammatory demyelinating disorders of the central and peripheral nervous system.     

手足口病患儿神经系统损害的观察及护理

目的：探讨手足口病患儿神经系统损害的观察及护理。方法通过对2011‐06—2014‐11在我院进行治疗的98例手足口病患儿进行分组，对照组给予对症护理，实验组实施综合护理干预。比较2组患儿治疗效果、护理满意度及并发症发生情况。结果实验组患儿治疗效果和护理满意度较对照组明显提高，并发症发生率显著降低，差异具有统计学意义（P＜0.05）。结论针对手足口病患儿采用综合护理干预可有效提高治疗效果及护理满意度，降低并发症发生率，提高患儿生活质量，值得临床推广应用。     

原发性中枢神经系统淋巴瘤诊疗进展

原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见的结外非霍奇金淋巴瘤,可累及脑,眼、软脑膜以及脊髓,具有高度侵袭性.PCNSL对放化疗及免疫治疗敏感,但单方案常短期内复发.目前公认的治疗包括诱导治疗和巩固治疗.本文就原发性中枢神经系统淋巴瘤的发病、进展以及治疗的研究进展做一综述.     

Neuroinflammation as modifier of genetically caused neurological disorders of the central nervous system: Understanding pathogenesis and chances for treatment

Genetically caused neurological disorders of the central nervous system (CNS) are usually orphan diseases with poor or even fatal clinical outcome and few or no treatments that will improve longevity or at least quality of life. Neuroinflammation is common to many of these disorders, despite the fact that a plethora of distinct mutations and molecular changes underlie the disorders. In this article, data from corresponding animal models are analyzed to define the roles of innate and adaptive inflammation as modifiers and amplifiers of disease. We describe both common and distinct patterns of neuroinflammation in genetically mediated CNS disorders and discuss the contrasting mechanisms that lead to adverse versus neuroprotective effects. Moreover, we identify the juxtaparanode as a neuroanatomical compartment commonly associated with inflammatory cells and ongoing axonopathic changes, in models of diverse diseases. The identification of key immunological effector pathways that amplify neuropathic features should lead to realistic possibilities for translatable therapeutic interventions using existing immunomodulators. Moreover, evidence emerges that neuroinflammation is not only able to modify primary neural damage‐related symptoms but also may lead to unexpected clinical outcomes such as neuropsychiatric syndromes.     

Concordance of quantitative damage within the diencephalon and telencephalon following systemic pilocarpine (380 mg/kg) or lithium (3 mEq/kg) / pilocarpine (30 mg/kg) induced seizures

We tested the hypothesis that a single systemic injection of 380 mg/kg of the muscarinic agonist pilocarpine would produce more diffuse and severe seizure-induced brain damage than a single injection of lithium (3 mEq/kg) followed 4 h later by < 1/10 the dosage of pilocarpine. The hypothesis was not supported; the pattern of quantitative brain damage 50–60 days after the seizures were elicited by either treatment was comparable within the limits of measurement error. Within the diencephalon and subcortica telencephalon the same structures were either damaged in a similar quantitative manner or were spared. Only five of the 119 damaged structures exhibited statistically significant treatment differences at P < 0.01. The results are compatible with the explanation that lithium may enhance the excitotoxic effects of subsequent muscarinic stimulation.     

Pathological and pathogenetic changes in the central nervous system of guinea pigs given tunicamycin

Summary Guinea pigs were injected with tunicamycin and the sequential morphological alterations in the brain examined to investigate further the pathogenesis of cerebral lesions in this experimental model of annual ryegrass toxicity, a central nervous system disease of livestock caused by members of the tunicamycin group of antibiotics. Brain damage was most commonly observed in the cerebellum, and the important alterations in the development of degenerative parenchymal lesions appeared to be largely referrable to changes in small blood vessels. Endothelial damage, with increased vascular permeability, resulted in capillary obstruction leading to localised ischaemia and hypoxic neuronal damage. There was evidence for several possible mechanisms which may have contributed to vascualr occlusion.Supported in part by a Wool Research Trust Fund grant     

Superficial siderosis of the central nervous system: pathogenetic heterogeneity and therapeutic approaches

OBJECTIVE: Superficial siderosis of the central nervous system (CNS) is a rare chronic progressive disorder caused by chronic subarachnoid hemorrhage. We present four patients with superficial siderosis of the CNS to describe the characteristic symptoms, and to discuss the pathogenetic heterogeneity and possible new therapeutic approaches. RESULTS: The causes of chronic subarachnoid bleeding in superficial siderosis were different. In two patients surgical treatment of ependymoma or cerebral cavernomas were the underlying diseases. No cause was detected in one patient. For the first time, we present one patient with vasculitis of the central nervous system associated with systemic hemochromatosis in superficial siderosis. Therapeutic approaches included exstirpation of cavernomas as the source of chronic bleeding in one patient, immunosuppressive therapy and venupunctures in the patient with vasculitis and hemochromatosis, and symptomatic treatment with chelating agents and antioxidants. The patients remained clinically stable for the follow-up period of up to 2 years. CONCLUSIONS: Our cases underline the pathogenetic heterogeneity of superficial siderosis and favor the early diagnosis for prompt initiation of therapy. Besides treatment of the underlying condition, antioxidants and radical scavengers may be effective in halting the progression of the disease.     

Amyloid angiopathy and granulomatous angiitis of the central nervous system: a case responding to corticosteroid treatment

Summary A 73-year-old woman presented with multifocal cerebral dysfunction of 1 month's duration. Cranial CT scanning revealed unusual widespread abnormalities. Brain biopsy showed amyloid angiopathy affecting vessels in the meninges and cerebral cortex, with associated granulomatous angiitis. There was no clinical evidence of extracranial vasculitis. Corticosteroid therapy produced striking clinical and radiological improvement.     

Lipid oxidative damage and distribution of inorganic arsenic and its metabolites in the rat nervous system after arsenite exposure: influence of alpha tocopherol supplementation

Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage). A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the final 20d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold reduction in TBARS levels when compared with rats that received iAs alone. These results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.     

原发性中枢神经系统神经母细胞瘤临床特征及预后分析

目的探讨原发性中枢神经系统神经母细胞瘤的临床特征及预后。方法回顾性分析采用手术治疗的8例原发性中枢神经系统神经母细胞瘤病人的临床资料,其中术后行单纯放疗4例,单纯化疗1例,放化疗1例。结果肿瘤全切4例,近全切除3例,部分切除1例。术后均经病理确诊为原发性中枢神经系统神经母细胞瘤。随访8例,中位随访时间21个月。术后复发5例,中位复发时间8个月,其中死亡4例,中位生存期24.5个月,存活1例。结论原发性中枢神经系统神经母细胞瘤临床罕见,需通过病理确诊。治疗宜采用肿瘤全切除术,术后辅助放化疗。     

Combination of lithium and electroconvulsive therapy (ECT) is associated with higher odds of delirium and cognitive problems in a large national sample across the United States

BackgroundLithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue.ObjectiveIn this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT + Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder?MethodsA national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N = 158), ECT (N = 64148), or ECT + Li (N = 422) after adjusting for demographics and psychiatric diagnoses.ResultsThe prevalence of delirium was higher in the ECT + Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT + Lithium have 11.7-fold higher odds (95% CI 7.55–17.99, P < 0.001) of delirium compared to ECT alone. In the ECT + Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania.ConclusionThese results are surprising given the fading concern about delirium association with ECT + lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.