Serial 1H-NMR spectroscopy study of metabolic impairment in primates chronically treated with the succinate dehydrogenase inhibitor 3-nitropropionic acid.

Previous studies in primates have shown that chronic systemic administration of the succinate dehydrogenase (SDH) inhibitor, 3-nitropropionic acid (3NP), replicates most of the motor, cognitive, and histopathological features of Huntington's disease. In the present study, serial 1H-NMR spectroscopy (1H-MRS) assessment of striatal and occipital cortex concentrations of N-acetylaspartate, phosphocreatine/creatine, choline, and lactate, were obtained every 2-weeks during the entire course of a chronic 3NP treatment in baboons. A region-selective increase in lactate was detected in the striatum of the 3NP-treated animals, either immediately before or in conjunction with a lesion in the dorsolateral putamen detected by T2-MR imaging. Absolute 1H-MRS quantitation demonstrated a progressive and region-specific decrease in striatal N-acetylaspartate, creatine, and choline, occuring as early as 3 weeks before the first detection of lactate. These results demonstrate that 1H-MRS can be used to monitor early stages of brain metabolic impairment. In addition, given that 3NP-induced SDH inhibition following systemic injection similarly affects all brain regions, the striatal selective decreases in N-acetylaspartate or creatine concentrations are not simply related to the level of mitochondrial impairment but to a preferential vulnerability of the striatum to 3NP-induced toxicity.     

大脑中动脉粥样硬化性狭窄患者卒中类型分析

目的研究大脑中动脉粥样硬化性狭窄或闭塞(MCAOD)患者的卒中类型及其发病机制。方法经TCD和(或)MRA确诊的症状性MCAOD的患者,依据头部弥散加权核磁成像(DWI)所示梗死灶的特点进行分类,并与MCA狭窄程度进行相关性分析。结果84例症状性MCAOD患者中,73.8%的患者表现为多发性脑梗死,主要累及内交界区(53.6%)、半卵圆中心(29.1%)和皮层(22.6%)。皮层区域内梗死、交界区梗死、深部小梗死灶的发生率分别为46.4%、56.0%和44.0%,以多发小灶性梗死为主,很少引起MCA主干支完全梗死。且皮层支完全梗死、半卵圆中心梗死与严重MCA狭窄有关,而腔隙样梗死多见于轻度MCAOD患者。结论MCAOD患者可表现为各种梗死类型,以交界区梗死最常见,且多发性脑梗死为MCAOD患者最常见的表现类型,主要累及皮层下白质等部位,病灶以链型或弧线型分布为特点,动脉-动脉栓塞为其发病机制之一;深部小梗死多为孤立病灶,与MCA主干粥样硬化斑继发的血栓堵塞豆纹动脉入口有关。     

Statistical voxel-wise analysis of ictal SPECT reveals pattern of abnormal perfusion in patients with temporal lobe epilepsy

OBJECTIVE: To investigate the pattern of perfusion abnormalities in ictal and interictal brain perfusion SPECT images (BSI) from patients with temporal lobe epilepsy (TLE). METHOD: It was acquired interictal and ictal BSI from 24 patients with refractory TLE. BSIs were analyzed by visual inspection and statistical parametric mapping (SPM2). Statistical analysis compared the patients group to a control group of 50 volunteers. The images from patients with left-TLE were left-right flipped. RESULTS: It was not observed significant perfusional differences in interictal scans with SPM. Ictal BSI in SPM analysis revealed hyperperfusion within ipsilateral temporal lobe (epileptogenic focus) and also contralateral parieto-occipital region, ipsilateral posterior cingulate gyrus, occipital lobes and ipsilateral basal ganglia. Ictal BSI also showed areas of hypoperfusion. CONCLUSION: In a group analysis of ictal BSI of patients with TLE, voxel-wise analysis detects a network of distant regions of perfusional alteration which may play active role in seizure genesis and propagation.     

Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients

Multiple sclerosis has a tendency to remit during pregnancy, followed by an increase in the risk for disease relapses in the postpartum period. In this communication, preliminary data are presented to indicate that activated peripheral blood mononuclear cells (PBMC) from the postpartum period secrete elevated levels of gamma-interferon (IFN-gamma) relative to those collected during the third trimester. In addition, myelin antigen-specific T cell lines established from the third trimester of pregnancy secrete elevated levels of interleukin-10. The data suggest that the study of the mechanisms underlying natural fluctuations in disease activity during pregnancy and the postpartum period holds promise for a better understanding of factors capable of initiating and regulating remission and exacerbation in MS.     

Alpha- 1-antitrypsin phenotypes and associated disease patterns in neurological patients

Introduction – Alpha-1-antitryp sin (AAT) deficiency is usually associated with lung or liver disease. It is often detected as a qualitative reduction of the alpha-1 band on the serum protein electrophoretic pattern. Material and methods – We examined the protein electrophoretic pattern in sera of 22980 unselected consecutive patients with neurological disorders and noted a reduced alpha-1 band in 88. Their phenotypes were compared with the clinical disease. Results – 75 patients had a deficient or non-M and 13 the usual MM phenotype. Contrary to in the general population, PiMZ was four times more common than PiMS. Vascular disease was more common in patients with PiMZ while multiple sclerosis significantly more frequents in patients with PiMS than with other phenotypes, including PiMM. Conclusions – Other genetic abnormalities have previously been found in AAT associated with multiple sclerosis, but not PiMS. Since PIMS leads to modest reduction of AAT activity, the association may be through other mechanisms than reduced protease activity.     

Verbal recall and recognition abilities in patients with Wilson's disease

Tests of memory and verbal fluency were administered to 19 neurologically impaired Wilson's patients, 12 non-neurologically impaired Wilson's patients and 15 normal control subjects. Wilson's patients with neurologic disease recalled significantly fewer words on the delayed recall version of the Rey Auditory Verbal Learning Test than control subjects (p less than .05) but they showed no impairment on the recognition version of this test. On a verbal fluency test (FAS) requiring the subject to retrieve items from different categories, Wilson's patients with neurologic disease generated significantly fewer words than control subjects (p less than .01). Results suggest that retrieval memory is mildly impaired in the neurologic WD group but rate of learning and rate of forgetting is normal.     

Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein.     

Differential patterns of memory loss in patients with Alzheimer's disease and Korsakoff's disease

Patients with Korsakoff's disease or the likely diagnosis of Alzheimer's dementia were tested on various mnemonic tasks and the results compared to the performance of alcoholic or normal controls. The experimental outcome indicates similar perceptual learning processes of Alzheimer and Korsakoff subjects. On the other hand, both groups of patients showed a somewhat different pattern of episodic memory loss, and a different proportion of intrusion and omission errors in the learning of semantically related words. The results are discussed with respect to some neuropathological and neuropsychological sequelae.     

肝豆状核变性患者MURR1基因全长编码序列的突变检测和分析

目的 研究我国肝豆状核变性（WD）患者MURR1基因的突变特征及其与WD患者临床表型的关系.方法 根据MURR1基因全长3个外显子及其毗邻内含子序列,自行设计合成引物,聚合酶链反应（PCR）扩增61例经ATP7B基因诊断确诊的WD患者的MURR1基因序列,PCR产物纯化后直接测序检测MURR1基因突变和多态,并以60名健康人作为对照.结果 1例患者在5＇非翻译区检出较为罕见的-43T→C杂合新多态,因例数太少,无法分析基因型和临床表型的关系.27例患者检出2号内含子的IVS2＋63C→G杂合多态,1例为纯合多态,频率为23.8%（29/122）;60名健康对照中,26名检出此杂合多态,3名为纯合多态,频率为26.7%（32/120）.通过χ^2检验,IVS2＋63C→G在健康对照和WD患者中的频率基本相等（χ^2=0.269,P＞0.1）,表明这是一个群体多态.在MURR1基因编码区和剪接位置均未发现突变或多态.结论 MURR1基因突变在我国WD患者中是罕见的,与我国WD患者的临床表型无相关性.     

Pallidal stimulation: Effect of pattern and rate on bradykinesia in the non-human primate model of Parkinson's disease

Deep brain stimulation (DBS) involves the delivery of continuous, fixed-frequency electrical pulses to specific brain regions; however the reliance of therapeutic benefit on the fixed-frequency nature of the stimulation pattern is currently unknown. To address this, we investigated the effect of changes in the pattern and frequency of DBS in the internal segment of the globus pallidus (GPi) on bradykinesia in a single, hemi-parkinsonian monkey. Therapeutic parameters (i.e., contacts, pulse width, amplitude) were established for fixed-frequency stimulation at 135 Hz based on improved movement times during a reach and retrieval task. Thereafter, the pattern and frequency of stimulation were varied to assess the effect of variability, bursting and oscillatory patterns of stimulation on bradykinesia. During fixed-frequency stimulation, performance improved as a function of increasing pulse rate (P < 0.01). Using a temporally irregular pattern at the same average frequency failed to alter therapeutic benefit relative to the fixed-frequency condition. Introducing an 80 Hz burst pattern (20 bursts/s at 4 pulses/burst) improved bradykinesia (P < 0.01) relative to both “OFF” and 80 Hz fixed-frequency conditions, yielding results comparable to fixed-frequency stimulation at 135 Hz with 40% less current drain. Compared to burst and fixed-frequency stimulations, oscillatory patterns at 4 and 8 Hz were less effective. These results suggest that lower frequency stimulation delivered in a regular bursting pattern may be equally effective and require lower energy than higher frequency continuous patterns of stimulation, thereby prolonging battery life and call into question the role of bursting activity in the pathogenesis of bradykinesia.     

颅内外直接、间接联合搭桥术治疗成人烟雾病25例临床分析

目的探讨颅内外直接、间接联合搭桥术治疗成人烟雾病的技术要点,评价其临床意义。方法回顾性分析25例成人烟雾病患者应用直接、间接联合搭桥术治疗效果,术中分别解剖游离出颞浅动脉额支、顶支,采用较粗一支行颞浅动脉—大脑中动脉M4段直接搭桥;另一支行脑硬脑膜动脉血管融通间接搭桥术。应用改良RANKIN量表(m Rs评分)和美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分评估患者手术前1天、术后1周及术后3个月的神经系统功能状态。结果 25例患者,行30侧联合搭桥术,23例术后1周内复查CT血管成像或DSA显示吻合口通畅,头部CT灌注成像显示脑血流量较术前增加,缺血症状改善。无死亡病例,患者的中位m RS评分由术前的3(1,3)分恢复到术后1周的2(1,3)分及术后3个月的1(0,3)分,差异有统计学意义(Z=15.14,P0.01)。患者的中位NIHSS评分由术前的5(4,8)分恢复到术后1周的4(2,7)分及术后3个月的3(1,4)分,差异有统计学意义(Z=11.36,P0.01)。1例患者术后合并对侧半球梗死,另1例合并术侧半球出血,均遗留偏瘫症状。结论颞浅动脉-大脑中动脉直接搭桥联合脑-硬脑膜-动脉血管融通间接搭桥术,可显著增加患者近期、远期脑血流量;围手术期血流动力学稳定是手术成功的关键。     

Brainstem 1H-MR spectroscopy in patients with Parkinson's disease with REM sleep behavior disorder and IPD patients without dream enactment behavior

OBJECTIVES: The objective of our study was to evaluate brainstem involvement by 1H-MR spectroscopy (1H-MRS) method in patients with idiopathic Parkinson's disease (IPD) with REM sleep behavior disorder (RBD) and IPD without dream enactment behavior. PATIENTS AND METHODS: We prospectively studied 12 IPD (3 females, 9 males) with a clinically and electrophysiologically confirmed RBD and 12 IPD (3 females, 9 males) patients without dream enactment behavior followed in Outpatient Clinics for Movement Disorders of Department of Neurology, Haseki Hospital. Using long and short TE single voxel 1H-MRS directed at ventral and dorsal pons, long TE NAA/Cr, Ch/Cr and short TE NAA/Cr, Ch/Cr, MI/Cr values of both groups were compared. RESULTS: Although no difference was found between groups with RBD and IPD without dream enactment behavior in demographic characteristics, duration of disease, mean levodopa dosage and duration of levodopa use, all UPDRS scores (total, motor and cognitive) were worse in RBD group (p<0.05). There was no statistically significant difference in long TE NAA/Cr, Ch/Cr and short TE NAA/Cr, Ch/Cr, MI/Cr values obtained in both groups (p>0.05). CONCLUSION: 1H-MRS does not detect marked metabolic differences in the pons in subjects with IPD with RBD and IPD without dream enactment behavior. This finding suggests either that present methodologies are not sensitive to detect subtle metabolic changes in the pons of subjects with RBD or that the primary lesion of RBD exists in other REM sleep-related brain regions beyond the pons such as the substantia nigra, the basal ganglia or the limbic system.     

The 3R principle and the use of non-human primates in the study of neurodegenerative diseases: the case of Parkinson's disease

The aim of this paper is to offer an ethical perspective on the use of non-human primates in neurobiological studies, using the Parkinson's disease (PD) as an important case study. We refer, as theoretical framework, to the 3R principle, originally proposed by Russell and Burch [Russell, W.M.S., Burch, R.L., 1959. The Principles of Humane Experimental Technique. Universities Federation for Animal Welfare Wheathampstead, England (reprinted in 1992)]. Then, the use of non-human primates in the study of PD will be discussed in relation to the concepts of Replacement, Reduction, and Refinement. Replacement and Reduction result to be the more problematic concept to be applied, whereas Refinement offers relatively more opportunities of improvement. However, although in some cases the 3R principle shows its applicative limits, its value, as conceptual and inspirational tool remains extremely valuable. It suggests to the researchers a series of questions, both theoretical and methodological, which can have the results of improving the quality of life on the experimental models, the quality of the scientific data, and the public perception from the non-scientist community.     

A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 1. Detection of repeated patterns

The existence of precise temporal relations in sequences of spike intervals, referred to as 'spatiotemporal patterns', is suggested by brain theories that emphasize the role of temporal coding. Specific analytical methods able to assess the significance of such patterned activity are extremely important to establish its function for information processing in the brain. This study proposes a new method called 'pattern grouping algorithm' (PGA), designed to identify and evaluate the statistical significance of patterns which differ from each other by a defined and small jitter in spike timing of the order of few ms. The algorithm performs a pre-selection of template patterns with a fast computational approach, optimizes the jitter for each spike in the template and evaluates the statistical significance of the pattern group using three complementary statistical approaches. Simulated data sets characterized by various types of known non stationarities are used for validation of PGA and for comparison of its performance to other methods. Applications of PGA to experimental data sets of simultaneously recorded spike trains are described in a companion paper (Tetko IV, Villa AEP. A pattern grouping algorithm for analysis of spatiotemporal patterns in neuronal spike trains. 2. Application to simultaneous single unit recordings. J Neurosci Method 2000; accompanying article).     

Differential deficits in expression recognition in gene-carriers and patients with Huntington's disease

Previous studies in symptomatic patients and asymptomatic gene-carriers of Huntington's disease (HD) reported a differential deficit in the recognition of facial expressions of disgust. This impairment may point to involvement of the basal ganglia in the recognition of disgust. In this study, we compared the performance of 20 patients with symptoms of HD, 20 gene-carriers of HD and 20 healthy controls on two tests of facial expressions in order to further investigate the role of the basal ganglia in disgust recognition. Recognition of fear, rather than disgust, was most severely impaired in the patients, who were also impaired at recognising expressions of anger, disgust and sadness. Direct testing for a differential deficit in disgust at the group level (and at the level of individual HD cases) revealed that the patients were in fact significantly more impaired on the other negative expressions than on disgust. The gene-carriers were not impaired on any expression, although there was a trend for the gene-carriers to be poorer at recognising fearful faces than the controls. We argue that the expression recognition performance of the patients and gene-carriers simply reflects differences in task difficulty, rather than dysfunction of any mechanisms dedicated to specific emotions. In contrast to previous studies in patients or gene-carriers of HD, our findings provide no evidence for a role of the basal ganglia in the recognition of disgust and cast doubt on whether results from HD patients and gene-carriers can be used in support of a double dissociation between recognition of disgust and fear.     

精神病患者暴力行为特征对照分析

目的探讨精神病患者暴力行为特征。方法对我院2003年-2006年进行的673例鉴定案例中,实施暴力行为且具有精神科诊断的为147例,设为研究组：实施暴力行为但不具有精神科诊断的66例,设为对照组。收集一般资料,进行BPRS、PANSS、汉密尔顿抑郁量表（HAMD）、社会功能适应量表（SDSS）以及MMPI、韦氏智力测查,然后进行数据分析。结果研究组病理动机占36%,2组BPRS、PANSS、HAMD、SDSS结果之间均存在显著性差异,一般资料、MMPI、韦氏智力测查之间无显著性差异。结论应加强对精神病人的积极治疗,减少精神病患者暴力行为的发生。     

A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis.

Paired cerebrospinal fluid and serum samples of patients with amyotrophic lateral sclerosis (n = 35) revealed no consistent abnormalities of CSF cell count, CSF albumin, CSF IgG, CSF IgM, IgG or IgM index, or oligoclonal immunoglobulin band formation in the CSF. Determination of IgG and IgM CSF and serum antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b, and GT1b showed a characteristic pattern which allowed the differentiation of amyotrophic lateral sclerosis from controls and from patients with other neurological disorders including multiple sclerosis. Specifically, patients with the disease had elevated CSF IgM antibodies to all gangliosides except AGM1. The lack of correlation between the CSF findings and corresponding serum antibodies suggests a chronic, compartmental, intrathecal immune response of low activity in amyotrophic lateral sclerosis. Whether this immune response is primary and of pathogenetic significance, or an epiphenomenon of neuronal degeneration, remains to be investigated.     

大脑中动脉严重狭窄或闭塞卒中类型分析

目的探讨大脑中动脉严重狭窄或闭塞患者卒中类型特点及其发病机制。方法经TCD确诊的大脑中动脉狭窄或闭塞患者,依据头部CT和(或)MRI所示梗死灶进行卒中分型。结果169例大脑中动脉严重狭窄或闭塞患者,卒中类型各亚型以腔隙性脑梗死(LI)最为常见,占38.46%,其次为分水岭梗死(WI)占19.23%。流域性脑梗死、弥散性多发点状脑梗死、半卵园中心梗死与MCA严重狭窄或闭塞程度有关。结论大脑中动脉严重狭窄或闭塞患者卒中类型以腔隙型脑梗死、分水岭梗死为主。卒中类型多种多样,血管检查应该作为缺血性脑血管病的常规检查。