急性视神经炎的轴突变性和炎症反应

Aims: To investigate whether plasma biomarkers for axonal injury and inflammation are related to loss and recovery of visual function in acute optic neuritis (ON).Methods: Eighteen patientswith ON and 14 controls were investigated in a longitudinal, prospective study. Plasma phosphorylated neurofilament heavy chain (NfHSMI35; a surrogate marker of axonal injury), nitric oxide metabolites (NOx), and citrulline (surrogate markers of inflammation) were measured. Results: Patients with ON had higher median plasma NfHSMI35 values than controls (0.17 versus 0.005 ng/ml; p < 0.05) and higher NOx values (49 versus 35.5μ M; p < 0.001). Plasma NfHSMI35 values correlated inverselywith visual acuity at presentation (R= 0.67; p=0.01). NfHSMI35 was higher in patients with poor recovery of visual acuity than in those with good recovery (0.25 ng/ml versus 0.09 ng/ml; p < 0.05). Three of four patients with high NfHSMI35 and high NOx values experienced a poor recovery as opposed to only one of five with high NOx but normal NfHSMI35 values. Conclusions: NfHSMI35, a surrogate marker for axonal damage, is a prognostic indicator and should be considered in the design of neuroprotective treatment strategies.

视神经炎引起视神经纤维层轴突丧失及视功能障碍

Axonal loss is thought to be a likely cause of persistent disability after amultiple sclerosis relapse; therefore, noninvasive in vivo markers specific for axonal loss are needed. We used optic neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in die macula with optical coherence tomography. We studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. Optical coherence tomography measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. There were highly significant reductions (P < 0.001) of RNFL thic kness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thicknessand visual acuity, visual field, color vision, and visual evoked potential amplitude. This study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect optic nerves from axonal loss.

急性视神经炎患者视神经平均面积的连续MRI研究

This study assessed optic nerve mean area on serial MRI in a cohort of patients with a first episode of acute unilateral optic neuritis to assess the effects of a single acute inflammatory demyelinating lesion. Twenty- nine patients with a median delay from onset of visual symptoms of 13 days (range 7- 24 days) were recruited. After a clinical examination and visual evoked potential (VEP) measurement, each patient had their optic nerves imaged with a coronal fat- saturated short echo fast fluid- attenuated inversion recovery sequence. Twenty- one patients had serial examinations after 2, 4, 8,12, 26 and 52 weeks. In addition, 32 control subjects had their optic nerves imaged up to three times. The mean cross- sectional area of the intra- orbital portion of each optic nerve was calculated by a blinded observer using a computer- assisted contouring technique. At baseline, the mean area of diseased optic nerves was 16.1 mm2 compared with 13.4 mm2 for healthy contralateral optic nerves (20.1% higher, P < 0.000 1) and 13.6 mm2 for controls (18.4% higher, P=0.000 3). The diseased optic nerve mean area declined over time, from initial swelling to later atrophy. The mean decline at 52 weeks was- 0.0018 mm2/day (95% confidence interval - 0.003 8 to - 0.000 51). At 52 weeks, the mean area of diseased optic nerves was 11.3 mm2 compared with 12.8 mm2 for healthy contralateral optic nerves (11.7% lower, P=0.032) and 13.1 mm2 for controls (13.7% lower, P=0.008). The 52 week diseased optic nerve mean area was not significantly affected by the baseline mean area. There was an association between baseline optic nerve mean area and logMAR visual acuity (rs=0.46, P=0.012) and visual field mean deviation (rs=- 0.55, P=0.002), but there was no evidence of an association between 1 year mean area and visual outcome. There was no evidence of association between baseline, rates of decline or 1 year diseased optic nerve mean areas and any of the baseline, 1 year or time- averaged VEP variables. The present study shows a consistent pattern of changes associated with individual inflammatory demyelinating lesions in the optic nerve. Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to visual impairment. Over the longer term, there was loss of tissue. The lack of association between 1 year optic nerve mean area and visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.

视神经炎后的视皮质选择性磁化传递率降低

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age-and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n=20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

早期复发-缓解型多发性硬化症患者的持续脊髓萎缩:一项为期3年的研究

Objectives: Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease. It is less clear how early it can be detected in relapsing-remitting (RR) MS, and whether early cord atrophy relates to the concurrent or future clinical course. Methods: Twenty seven RR MS patients (median disease duration 1.7 years, in all cases < 3 years from onset) were recruited along with 20 controls. They were followed for up to 3 years with a yearly assessment of UCCA and clinical function measured by the Expanded Disability Status Scale (EDSS) and MS Functional Composite Score (MSFC). Clinical and MRI correlations were investigated. Statistical models adjusted for covariates including total intracranial volume. Results: Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume. Conclusions: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.

视神经炎导致视皮质的选择性磁化传递率下降

Patients with clinically isolated syndromes suggestive of multiple sclerosis have evidence for abnormality in normal appearing grey matter detected using the magnetization transfer ratio (MTR), a quantitative MRI measure. One potential mechanism for the decreased grey matter MTR (GM MTR) observed is trans-synaptic morphological abnormality secondary to demyelinating lesions that are in an anatomically linked pathway but remote location. We investigated this potential association by studying the location of abnormalities using voxel-based analysis of GM MTR maps in a group of 80 patients studied within 6 months of presenting with isolated optic neuritis and compared the findings with those seen in 50 age-and sex-matched healthy controls. Occipital cortex and whole brain analysis comparing all optic neuritis patients and controls revealed a selective decrease of MTR bilaterally in the visual cortex in patients [Brodmann area (BA) 17]. Whole brain analysis of patients fulfilling the McDonald criteria for multiple sclerosis (n = 20) showed a lower MTR compared to controls bilaterally in the visual cortex (BA 17/18), left hippocampus, bilateral superior temporal gyrus, bilateral lenticular nuclei and the right cerebellum. There was no significant difference in the percentage of grey matter between patients and controls in the regions of abnormal MTR detected in the visual cortex. The intrinsic MTR decrease seen in patients suggests that there are structural changes in the visual cortex following an attack of optic neuritis. Potential mechanisms for this include trans-synaptic neuronal degeneration and cortical synaptic morphological changes; such abnormalities may also contribute to MTR abnormalities observed in the normal appearing grey matter in multiple sclerosis.

脑脊液常规检查指南 EFNS特别工作组的报道

许多神经系统疾病都需要通过脑脊液(CSF)检查来确诊或排除相关的鉴别诊断。本文的目的是评价CSF常规检查的理论背景并为其临床应用提供指南,包括总蛋白、白蛋白、免疫球蛋白、葡萄糖、乳酸盐、细胞计数、细胞染色和感染性CSF的检查。研究方法包括对上述指标的系统Medline检索以及由一位或多位特别工作组成员对相关文献进行评价。在特别工作组全体成员共识基础上对证据和推荐意见进行分级。建议CSF应在采集后立即送检。如果需要贮存,应将12 mL CSF分装3～4只无菌试管。推荐测定CSF/血清白蛋白比率(Q_(alb))而不是总蛋白水平,其正常上限应与患者年龄相关。Q_(alb)升高是一种非特异性表现,但主要见于细菌性、隐球菌性和结核性脑膜炎、软脑膜转移瘤以及急性和慢性脱髓鞘性多发性神经病。CSF/血清葡萄糖比率的病理性下降或乳酸盐浓度升高提示细菌或真菌性脑膜炎或软脑膜转移瘤。通过在等电聚焦电泳后进行特殊染色可完美证实鞘内免疫球蛋白G合成。只要发现脑脊液细胞增多或怀疑软脑膜转移瘤或病理性出血,就应进行细胞形态学(细胞染色)评价。对于CT扫描结果阴性的鞘内出血,应进行胆红素检测。