【作者】 李咏梅；

【导师】 谢鹏；

【作者基本信息】 重庆医科大学 ， 神经病学， 2008， 博士

【摘要】 背景原发性脱髓鞘病变主要包括多发性硬化（multiple sclerosis, MS）、视神经脊髓炎（neuromyelitis optica, NMO）和急性播散性脑脊髓炎（acute demyelinating encephalomyelitis,ADEM）等疾病。MS是常见的神经科疾病,在发达国家是造成中青年非外伤性致残的首要原因。我国属于MS的中发区。目前MS的病因和发病机制未明,其诊断标准也在不断修订。MRI是MS最重要、最敏感的影像检查工具,包括常规和功能MR成像,对该病的诊断、治疗后的随访以及诠释疾病的病理生理等特点具有不可替代的作用。NMO与MS的关系目前尚无定论。既往认为NMO属于选择性累及视神经和脊髓的单相性疾病。目前的证据显示,NMO也呈多相性,并亦可累及CNS其它结构,在临床、影像学和免疫病理等方面与MS有明显区别。目的分析重庆地区MS患者常规MRI和氢质子磁共振波谱（1H-MRS）成像代谢特点。探讨扩散加权成像（DWI）的定量指标表观扩散系数（ADC）值对MS各种病灶的评估价值。探讨NMO脑部MRI影像特点,对鉴别MS与NMO、建立NMO的诊断标准提供帮助。最后评估MS患者MRI影像特点与临床MS各种评分的相关性。方法1.以重庆医科大学附属第一医院和本市其他部分三甲医院神经内科就诊的门诊、住院和随访的MS和NMO患者作为研究对象。2. 180例MS患者均符合2005年修订的McDonald诊断标准,按照国际MS诊断小组制定的MRI扫描序列,所有患者作脑部、脊髓和视神经扫描。3.对部分依从关系较好的MS患者作1H-MRS扫描,采用多体素和单体素分析MS不同病灶、不同亚型之间的代谢差别。4.将60例临床确诊的RRMS型纳入研究对象,比较不同信号病灶ADC值是否有统计学差别。5.符合2006年Wingerchuck诊断标准的NMO患者纳入研究对象,按照标准的MS扫描方法,分析脑部MRI正常和异常影像特点。6.由一位神经科医师在不知道影像学结果的条件下对所有患者进行EDSS评分、MS生活质量54项评分（MSQOL-54）和简易智力状态检查量表（MMSE）评分,所有评分与MRI检查在同一天完成,分析常规和功能MR成像相关影像特点与临床各种评分的相关性。结果1.据病灶累及部位:单纯脑部受累最多共82例（45.56%）,单纯脊髓受累53例（29.44%）,脑和脊髓均受累45例（25%）。2.脊髓病灶中,下颈髓和上胸髓最易受累,≤3个椎体节段的病灶数占了74.49%,而>3椎体节段的病灶数占了25.52%。3. PD/T2WI和FLAIR像对幕下、侧脑室周围以及深部灰白质交界区病灶的检出率比较没有统计学差异（p>0.05）,对皮质及皮质下病灶,FLAIR较T2WI病灶的检出率高,二者有统计学意义（p<0.05）。4. RRMS和进展型MS与对照组NAWM区NAA/Cr、Cho/NAA、Cho/Cr有明显统计学差异,P<0.01;强化病灶、非强化病灶与对照组的NAA/Cr、Lac+Lip/Cr有统计学差异,p<0.05;急性病灶Cho、Lac+Lip升高,NAA不同程度降低;扣带回与对照组NAA/Cr和Cho/Cr无统计学差异,p>0.05。5. ADC值结果:低信号与等信号病灶ADC值分别为（127.54±9.31）×10^-5 mm²/s和（95.71±6.25）×10^-5 mm²/s,二者统计学差异（P<0.05）;融合与分散病灶ADC值分别为（141.35±6.51）×10^-5 mm²/s和（105.38±13.89）×10^-5 mm²/s,二者有统计学差异（P<0.01）。6. NMO脑部MRI结果:脑内有异常表现28/33例（84.8%）,脑实质有明确病灶22例（66.7%）,幕上近皮质、皮质下和深部脑白质区的点状非特异性病灶最多;幕下脑干是易受累的部位（14/33, 42.4%）,特别是延髓（7/33, 21.2%）。7.单纯脊髓受累、单纯脑部受累和脑脊髓混合受累MS患者的EDSS评分有统计学差异（P<0.05）,脊髓萎缩与EDSS评分之间无相关性(r=2.31,P=0.2516,但与病程呈明显相关,r=0.40, P=0.0267。NAA/Cr与EDSS评分呈负相关p<0.05;NAA/Cr、Ins/Cr与病程呈正相关,p<0.05。单纯脑受累的MSQOL-54评分与单纯脊髓受累、脑脊髓均受累患者的相应评分之间有统计学差异（P<0.01）;扣带回NAA/Cr与认知功能（MMSE）评分之间有明显相关性,p<0.05。结论1.常规MRI扫描是诊断MS最敏感的影像技术,本研究支持MS是一个累及全脑的弥漫性病变,增加脊髓扫描有助于提高MS诊断的敏感性以及与其他疾病的鉴别诊断。2.采用PD/T2WI和FLAIR像,改善MRI对MS病灶检出的定量诊断能力,特别是FLAIR像对诊断皮质及皮质下病灶较好,PD/T2WI对后颅窝的显示较好。3.通过1H-MRS对MS不同亚型和各种病灶的波谱比较,阐述了MS不同亚型和病灶中神经元的轴索和髓鞘破坏、胶质增生以及炎性反应等病理生理异质性。4.通过各种病灶ADC值的定量分析对解释MS病灶的病理变化、监测其病程有一定的价值。5. NMO患者出现脑内非特异病灶很常见,有脑部病变不能排除NMO的诊断,本研究的结果有助于NMO诊断标准的修订。6.单纯脊髓受累、单纯脑部受累和脑脊髓混合受累MS患者的EDSS评分和认知功能均有统计学差别,单纯脑损害MS患者的MSQOL-54生活质量最好。不同的代谢率与EDSS评分、MSQOL-54评分以及病程之间的相关性不同。更多还原

【Abstract】 BackgroundThe primary demyelinating diseases include multiple sclerosis （MS）, neuromyelitis optica （NMO）, acute demyelinating encephalomyelitis （ADEM） and so on. MS is one of the most important neurological diseases, which is the leader cause of non-trauma disability among youths in developed country. Now China is considered as a medium incident area. At present, the pathogenesis of MS is not clear and the diagnostic criteria for MS change constantly. Magnetic resonance imaging （MRI） is the most important and most sensitive imaging diagnostic tool. It is important value to diagnose, follow up after therapy and explain the patho-physiology for MS with the conventional and functional MRI, and is unable to be substituted.No final conclusion has yet been reached for NMO and MS, and no golden diagnostic criteria for NMO are found. NMO is an idiopathic inflammatory demyelinating disorder that was thought to preferentially affect the optic nerves and spinal cord but without brain MRI abnormalities. Lots of other evidences suggested that NMO differs MS from clinical presentations, experimentation findings, image features, immunopathologic characteristics and therapeutics. It is of great importance to display brain abnormalities of NMO and discriminate diagnosis for NMO and MS with MRI scans.PurposesThis study was to identify image characteristics and metabolite changes in patients with MS in the district of Chongqing with the conventional MRI and 1H-proton MR spectroscopy （1H-MRS）, to explore the values of diffusion-weighted imaging（DWI）and apparent diffusion coefficient （ADC） measurements in various pattern lesions of MS, to identify brain abnormalities in NMO by MRI, which are helpful to the revision of diagnostic criteria for NMO. At last this study was to evaluate the correlations between the various image features and clinical scores of MS patients.Methods1. The following-up outpatients and hospitalization of clinically diagnosed patients with MS and NMO were included at the First Affiliated Hospital of Chongqing Medical University and other hospitals in Chongqing.2. 180 Patients who fulfilled the MS diagnostic criteria of McDonald et al were selected to perform MRI scans of the brain, spinal cord and optic nerves. The brain and spinal cord images were analyzed. 3. Some patients with MS who can endure a long time MRI scans were selected to perform 1H-MRS. The metabolite difference of various pattern lesions and subtypes of patients with MS were analyzed with multiple-voxel long and short echoes, single-voxel short echo magnetic resonance spectrum.4. 60 patients with clinically diagnosed remitting-relapsing MS （RRMS） were included and underwent conventional brain MRI and DWI scans, mean ADC values were measured for various lesions of MS. The statistical analyses were performed to determine the differences of mean ADC values among various lesions of MS.5. Patients who fulfilled the latest diagnostic criteria of NMO proposed by Wingerchuk et al were selected to perform standard MRI scans of the brain, spinal cord and optic nerves. The normal and abnormal brain images were analyzed.6. Expanded Disability Status Scale （EDSS）, Multiple sclerosis quality of life-54 instrument （MSQOL-54） and Mini-Mental State Examination （MMSE） of all patients were scored within the same day of MRI scans by a professional neurologist. The correlations were analyzed between MRI findings and clinical various scores.Results1. The patients with simple brain lesions were involved in 82 cases （45.56%）, for spinal cords , 53 case（s29.44%）,for both brain and spinal cord, 45 cases（25%）,based on the locations of lesion involvements.2. The lower cervical and upper thoracic spinal cords for patients with MS were easily involved; the length of cord lesions which were less than three vertebral segments was 74.49%, for more than three vertebral segments, 25.52%.3. The detection rates with PD/T2WI and FLAIR imagings were no statistical differences among infratentorium, surroundings of cerebral lateral ventricles and deep white matter（p>0.05）.The statistical difference was found between the FLAIR and T2WI in cortical and subcortical lesions（p<0.05）.4. The metabolite ratios of NAA/Cr,Cho/NAA and Cho/Cr in normal-appearing white matter （NAWM） are statistical differences among RRMS, progressive MS and the control group （P<0.01）. The metabolite ratios of NAA/Cr and Lac+Lip/Cr are significant different between the enhanced lesions, non-enhanced lesions and the control group （p < 0.05） , The Cho and Lac + Lip peaks are revealed elevatation markedly in acute plagues and NAA peak is displayed decrease. However, the metabolite ratios of NAA/Cr and Cho/Cr are not statistical different between the cingulate gyrus and the control group （p>0.05）.5. The ADC values of hypointense lesions were significantly higher than that of isointense lesions （ P < 0.001 ） , the ADC values were （127.54±9.31）×10^-5 mm²/sec and（95.71±6.25）×10^-5 mm²/sec respectively. The ADC values of confluent lesions had a substantially higher than that of discrete lesions（P<0.001）, the ADC values were（141.35±6.51）×10^-5 mm²/sec and（105.38±13.89）×10^-5 mm²/sec respectively. No correlation was found between ADC values of lesions and EDSS scores（P>0.05）.6. Brain abnormal findings of NMO were detected in 28 out of 33 patients （84.8%）. 22 patients （66.7%） showed well-defined brain parenchymal lesions. In the supratentorial lesions,most were punctate or small round dots and nonspecific hyperintensities in juxtacortical,subcortical and deep white matter regions. In the infratentorium,brainstem was an easily involved region （14/33, 42.4%）, especially in medulla （7/33, 21.2%）.7. The EDSS scores were statistical difference among the patients with simple brain involvement, simple spinal cord involvement, both brain and spinal cord involvement（sP<0.05）. The MSQOL-54 scores of MS with simple brain involvement were significantly higher than those of the two later subtype（sP<0.05）. There was no correlation between the spinal cord atrophy and EDSS scores （r=2.31,P=0.2516）, but rather than that of disease course （r=0.40, P=0.0267）. There was negative correlation between the NAA/Cr ratio and EDSS scores, （p<0.05）. A significant correlation was found between the NAA/Cr ratio of the cingulate gyrus and cognition function （p<0.05）, but for that of EDSS scores, no correlation was found （p>0.05）.Conclusions1. The conventional MRI is the most important tool for diagnosis of MS. It is helpful to renew the concept that only brain white matter was involved. In fact, the whole brain is diffusing involved in patients with MS. Spinal cord MRI scans can improve the sensitivity of the diagnosis and differential diagnosis of MS from other diseases.2. The PD, T2WI and FLAIR can improve the quantity diagnostic ability of the lesions for MS; especially the cortical and subcortical lesions are detected well by FLAIR images. The lesions of the posterior cranial fossa are displayed well by PD and T2WI.3. The pathophysiological heterogeneities including the axial damages, myelinolysis, gliosis and inflammatory reactions are explained well by the 1H-MR spectrum among the subtypes MS and various pattern lesions.4. DWI and quantitative ADC measurements are useful tools to explain the pathological changes in different lesions and monitor the disease duration of MS.5. Non-specific abnormalities in brain MRI are common in Chinese NMO patients, and the patients with brain lesions do not exclude the diagnosis of NMO. The observation of brain lesions is helpful to improve and revise diagnostic criteria of NMO.6. The scores of EDSS and cognition function in the subtypes （simple spinal cord involvement, simple brain involvement, both brain and spinal cord involvement） are all different. The MSQOL-54 is observed the best in simple brain involvement. The different correlations are found between the different metabolite ratios and EDSS scores, and disease courses and MSQOL-54 scores.更多还原