Cognitive functions in neuromyelitis optica

BACKGROUND: Neuromyelitis optica (NMO) is characterized by optic neuritis and longitudinally extensive acute transverse myelitis. The brain is generally considered healthy in NMO, though very recent studies have demonstrated that magnetic resonance imaging abnormalities may be observed in various brain regions of NMO patients. To date, cognitive functions have never been investigated in NMO. OBJECTIVE: To investigate cognitive functions in a cohort of 30 patients with NMO. DESIGN: Observational, prospective study. PATIENTS: We studied 30 patients with NMO and compared them with 30 patients with multiple sclerosis and 30 healthy controls matched for age, sex, and educational level. Main Outcome Measure We applied a French translation of the Brief Repeatable Battery of Neuropsychological Tests for Multiple Sclerosis and 3 additional tests. RESULTS: Cognitive performance was significantly lower in the NMO and multiple sclerosis groups than in healthy controls for the 2-second (P< .001) and 3-second (P= .001) Paced Auditory Serial Addition Test, the digit symbol modality test (P= .005), word generation (P= .02), and forward (P= .002) and backward (P= .007) digit span test. We did not observe any difference in test performance between NMO and multiple sclerosis patients. We found no differences between the 3 groups for the other tests. We did not find any correlation between clinical, biological, or magnetic resonance imaging results and cognitive dysfunction. CONCLUSIONS: This study confirms the recent concept of a possible brain involvement in NMO. Additional studies are needed to confirm these initial results and to better understand the mechanisms of such abnormalities.     

Devic's neuromyelitis optica: a critical review

Devic's neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI) studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.     

Cognitive telerehabilitation in neurological patients: systematic review and meta-analysis

Neurological Sciences - Telerehabilitation (TR) seems to be an encouraging solution for the delivery of cognitive treatments in patients with neurological disorders. This study was aimed to analyze...     

Retina thickness in clinically affected and unaffected eyes in patients with aquaporin-4 immunoglobulin G antibody seropositive neuromyelitis optica spectrum disorders: a systematic review and meta-analysis

Journal of Neurology - Retina thickness has been studied in patients with neuromyelitis optica spectrum disorders (NMOSD) without distinguishing serostatus and limited data are available in...     

Declarative memory in unaffected adult relatives of patients with schizophrenia: a systematic review and meta-analysis

Despite evidence for diverse neuropsychological impairment in schizophrenia, verbal declarative memory has emerged as a core deficit in the disorder. Similar but less marked impairments have been demonstrated in unaffected biological relatives of patients with schizophrenia, but the nature and extent of the memory impairment in relatives compared to controls is unclear. We have conducted a systematic review and meta-analysis of the literature investigating declarative memory in unaffected biological relatives of schizophrenics and controls, with the aim of quantifying memory deficits in relatives. The standardised mean difference between groups was calculated for nine measures of declarative memory and two measures of intellectual ability, based on 21 studies of several hundred relatives of schizophrenics and controls. Unaffected relatives showed poorer performance relative to controls on all tests of memory examined. Small to moderate effect sizes, with overlapping 95% confidence intervals, were greatest on immediate (trial 1) list recall (0.65), followed by immediate (0.53) and delayed story recall (0.52). Verbal and general IQ showed smaller standardised mean differences as the latter tests, while the smallest standardised mean difference was shown on delayed visual recall (0.32). Results suggest greater deficits on tests of increasing memory load or which place demands on effective encoding processes but more studies with these tasks are needed. Investigation of sub-groups within these cohorts (e.g. age groups within or beyond the maximum age of risk) is recommended in order to identify deficits specific to the disease process.     

Th17 cells in neuromyelitis optica spectrum disorder: a review

Neuromyelitis optica spectrum disorder (NMOSD) has been identified as a central nervous system (CNS) autoimmune inflammatory disorder, which has been recognized as a B cell-mediated humoral immune disease. However, cases have been reported indicating that some of the neuromyelitis optica (NMO) patients have been resistant to B cell-related treatments. Recently, more and more evidence has shown that T cell-mediated immunity may take part in the pathogenesis of NMOSD, especially in the Th17 phenotype. In our PUBMED search, we used the following keywords: Th17 cell, Th17 cell-related cytokines, T cells, B cells, B cell-related productions, NMO, NMOSD, recurrent/bilateral optic neuritis, recurrent transverse myelitis and longitudinally extensive transverse myelitis. We systemically reviewed the role of Th17 cells and Th17 cell-related cytokines in NMOSD. We found that Th17 cells and Th17-related cytokines, such as IL-6, IL-1β, IL-17, IL-21, IL-22, IL-23 and TGF-β, are not only directly involved in the pathogenesis but also collaborated with B cells and B cell-related antibody production to induce CNS lesions. Th17 cell-related therapy has also been reviewed in this article, and the data suggested that Th17 may be a new therapeutic target of NMOSD.     

Rituximab in neuromyelitis optica: A review of literature

Neuromyelitis optica spectrum disorders, or neuromyelitis optica(NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse prevention in NMO include immunosuppressants and monoclonal antibodies. Rituximab, a monoclonal antibody that targets CD20 antigen expressed on the surface of pre-B, mature B-lymphocytes and a small subset of T-lymphocytes, has been widely used for the treatment of NMO. In this review, we aim to summarize global experience with rituximab in NMO. We identified 13 observational studies that involved a total of 209 NMO patients treated with rituximab. Majority of rituximab-treated patients evidenced stabilization or improvements in their disability scores compared to pre-treatment period and 66% of patients remained relapse-free during treatment period. Monitoring rituximab treatment response with CD19+ or CD27+ cell counts appears to improve treatment outcomes. We offer clinical pointers on rituximab use for NMO based on the literature and authors' experience, and pose questions that would need to be addressed in future studies.     

HIV感染合并视神经脊髓炎谱系疾病一例报道并文献复习

目的总结HIV感染合并视神经脊髓炎谱系疾病(NMOSD)患者的临床特点,以提高临床对其认识。方法报道作者医院收治的1例以视神经脊髓炎症状起病的AIDS患者的临床资料,并结合文献进行复习。结果文献检索HIV感染合并NMOSD患者7例,结合本文报道的1例共8例,年龄8~55岁,平均(39.1±14.4)岁,其中男5例、女3例。8例患者均发生脊髓炎,7例发生视神经炎。血CD4+T细胞降低3例(3/8)。脑脊液(CSF)细胞学检测异常4例(4/8),表现为白细胞轻度升高,以淋巴细胞炎性反应为主,6例蛋白水平升高(6/8)。血清水通道蛋白4抗体阳性3例(3/7)。CSF寡克隆区带阳性3例(3/5)。MRI检查显示颅内多发病灶2例(2/8),颈段或胸段脊髓病灶8例(8/8),其中4例为颈髓至胸髓连续长节段病灶。8例患者接受免疫治疗,其中7例接受糖皮质激素治疗,3例(3/8)肌力完全恢复或能独立行走,1例(1/8)肌力部分恢复,4例(4/8)肌力无明显恢复,3例(3/7)视力恢复至粗测正常,1例(1/7)视力部分恢复,3例(3/7)失明。复发5例,其中4例1年内复发。1例死亡。结论HIV感染合并NMOSD患者致残率高,易复发,部分患者免疫治疗有效。     

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.     

视神经脊髓炎患者生活质量调查

目的观察视神经脊髓炎(neuromyelitis optica,NMO)患者扩展残疾状况量表(expanded disability status scale,EDSS)评分、病程、年龄、性别及水通道蛋白4(AQP4)-IgG与生活质量的关系,初步探讨影响NMO患者生活质量的因素。方法对40例NMO患者进行EDSS评分,填写国外广泛使用于NMO患者的中文版简化36医疗结局研究量表(MOSSF-36,简称SF-36量表),分别对NMO患者的EDSS评分、病程、年龄、AQP4-IgG与SF-36量表评分的相关性进行分析。结果 NMO患者EDSS评分与生活质量中生理健康呈中度负相关(r=-0.572,P=0.0001),与心理健康无相关性(r=-0.284,P=0.075)。其中EDSS评分与SF-36量表8个维度中的生理机能(r=-0.484,P=0.002)、生理职能(r=-0.532,P=0.0004)、躯体疼痛(r=-0.386,P=0.014)、一般健康状况(r=-0.420,P=0.007)、精力(r=-0.378,P=0.016)和社会功能(r=-0.373,P=0.018)均呈负相关,与"健康变化"这一项呈低度正相关(r=0.347,P=0.028),而与"情感职能"和"精神健康"两项无相关性(均P0.05)。年龄仅与生理健康(r=-0.390,P=0.013)和其中生理功能(r=-0.498,P=0.001)这一维度呈负相关,病程、性别、AQP4-IgG与生活质量均无相关性(均P0.05),EDSS评分与年龄呈低度正相关(r=0.384,P=0.015)。结论 EDSS评分可作为NMO患者生活质量尤其是生理健康的一个预测因子,临床可常规评定NMO患者EDSS得分,从而指导临床医生关注患者生活质量并进行必要干预。     

Treatment of neuromyelitis optica: an evidence based review

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.     

Brain MRI abnormalities in Brazilian patients with neuromyelitis optica

Brain abnormalities in neuromyelitis optica (NMO) have been reported previously, but the pathophysiological mechanism and clinical relevance of these abnormalities are poorly understood. We assessed the prevalence and patterns of brain MRI abnormalities in a Brazilian cohort of patients with NMO. Conventional brain MRI and medical records from 24 Brazilian patients with NMO were retrospectively evaluated. Brain MRI were classified into four subgroups: normal, non-specific lesions, multiple sclerosis (MS)-like lesions, and typical lesions. Brain lesions were detected in 19 patients (79.2%). Fourteen patients (58.3%) had non-specific lesions, three (12.5%) had MS-like lesions, and two (8.3%) had typical lesions. Differences between these subgroups with respect to the Expanded Disability Status Scale (EDSS) scores (p=0.86) were not significant. This study demonstrates a high prevalence of brain abnormalities in Brazilian patients with NMO; however, we did not find a significant relationship between these abnormalities and EDSS scores.     

视神经脊髓炎脑脊液改变的特点

目的　分析视神经脊髓炎 (NMO)患者的脑脊液 (CSF)改变特征。方法　对 56例NMO患者的临床资料 ,66次腰穿CSF检查结果进行分析。结果　①NMO分为单纯型和复发型 ;CSF细胞数在两型都有轻度增高 ,但单纯型同时多伴有全身炎症反应 ,复发型多不伴发急性炎症 ;②两型均有蛋白轻中度增高 ;③CSF中IgG在复发型增高 ,尤其以发展为多发性硬化 (MS)者显著 ;④蛋白 细胞分离现象仅见于NMO两型患者 ,MS者无此现象 ;⑤CSF细胞学检查两型均无特异性。结论　利用CSF特点对NMO两型患者及发展为MS者可进行诊断、鉴别诊断和治疗指导     

Cognitive reserve in Parkinson's disease: A systematic review and meta-analysis

BackgroundThe concept of cognitive reserve is proposed to explain the mismatch between the degree of pathological changes and their clinical manifestations and has been used to help understand the variation in the rate of cognitive decline and the development of dementias. It is not clear whether this concept applies to cognitive performance, cognitive decline and dementia in Parkinson's disease (PD).MethodsA systematic review was conducted using the most commonly described proxies for cognitive reserve of education, occupation and leisure activities. Thirty four papers were found on education and cognition in PD but there were no studies of the other proxies of reserve. A random effects meta-analysis was used to assess the associations between education and cross-sectional cognitive assessments, longitudinal global cognitive decline and a long term dementia diagnosis.ResultsThere was a significant association between higher education and cross-sectional performance of MMSE, global cognition, mild cognitive impairment, attention, executive function, visuospatial function and memory. There was a small but significant association between higher education and a reduced rate of cognitive decline. There was no association with a final dementia diagnosis. There was not enough information to perform an analysis on the rate and timing of transition to dementia.ConclusionsHigher levels of education are associated with significantly better cognitive performance and a small but significant slowing in cognitive decline but are not associated with a reduction in long-term dementia in PD. More detailed, standardized, longitudinal studies are required to study conclusively the effects cognitive reserve in PD.     

视神经脊髓炎患者血清 NMO-IgG 检测及其诊断价值

目的 检测神经脊髓炎(neuromyelitis optica,NMO)患者血清NMO-IgG的表达,并探讨其在NMO诊断中的价值.方法 收集北京、辽宁丹东、山西大同三家医疗机构临床诊断为NMO患者26例、多发性硬化(multiple sclerosis,MS)患者32例、神经科其他疾病患者77例;以稳定表达人源水通道蛋白-4(aquaporin-4,AQP4)的人胚肾293(HEK293)细胞株为底物,应用间接免疫荧光法检测患者血清NMO-IgG水平.结果 16例(61.5%)NMO患者血清NMO-IgG阳性,其阳性检出率显著高于MS患者(9.4 %)和MS+神经科其他疾病患者(4.6 %)(P<0.01).NMO-IgG对NMO诊断的灵敏度为61.5%,以MS作为对照时,该抗体对NMO诊断特异度为90.6%,以MS+神经科其他疾病作对照时,其特异度为95.4%.结论 NMO患者血清中普遍存在NMO-IgG,其可作为国内NMO诊断的重要生物学指标.