dxy

网友[leleworm]：

MS一定是缓解、复发的病程吗？
不是
About 85% of patients with multiple sclerosis present with the relapsing-remitting form, comprising episodic relapses and remissions that may be partial or complete.
About 15% of patients present without relapses but show a slowly progressive pattern called primary progressive multiple sclerosis.

MS一定仅累及白质吗？MS除了病灶以外的白质是否是健康的？
都不是
Evidence now suggests widespread involvement, even in normal appearing white matter, and extensive involvement of grey matter and damage to axons. Damage to axons may be the more important aspect of multiple sclerosis and the basis of the disease's eventual and mostly irreversible progression.

参考文献：Diagnosis and treatment of multiple sclerosis.BMJ 2006;332:525-527

MS的DWI和脑卒中如何鉴别？

鉴别点是环形强化和深部白质病灶
Topics in Magnetic Resonance Imaging 11(5): 300–309
Diffusion-Weighted Imaging as a Problem-Solving Tool in the Evaluation of Patients with Acute Strokelike Syndromes
Whereas most acute multiple sclerosis plaques demonstrate increased diffusion rarely, acute multiple sclerosis plaques have restricted diffusion . This may result from cytotoxic edema or from increased inflammatory cellular infiltration with little extracellular edema. These plaques may demonstrate a ring-enhancing pattern that differentiates them from acute infarctions. However, occasionally, nonenhancing acute plaques may resemble acute infarctions. In a young patient with a white matter lesion characterized by restricted diffusion, it is important to search for other lesions. Associated deep white matter lesions may suggest a demyelinative process,whereas associated cortical lesions may suggest an ischemic process.

MS一定是炎症的过程吗？有无缺血、neurodegeneration的参与？

MS进展性不可逆性神经功能缺损有neurodegeneration的参与
J Neurol. 2005 Nov;252 Suppl 5:v3-9.
The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage.
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system manifested morphologically by inflammation, demyelination, axonal loss and gliosis. The inflammatory lesions are characterized by massive infiltration by a heterogeneous population of cellular and soluble mediators of the immune system, including T cells, B cells, macrophages and mi croglia, as well as a broad range of cytokines, chemokines, antibodies, complement and other toxic substances. The appearance of such lesions is associated with clinical relapses. Recent detailed immunopathological studies of early, acute lesions revealed profound heterogeneity in the patterns of demyelination and the factors of the immune system involved. During remission, resolution of inflammation is the main factor which leads to clinical improvement of patients. However, the immune system can play a beneficial role at this stage, promoting remyelination perhaps by production of growth factors such as BDNF. In contrast, the progressive irreversible neurological deficit in multiple sclerosis is associated with neurodegenerative processes resulting in axonal and neuronal loss. The mechanisms behind damage to axons in multiple sclerosis lesions are poorly understood. However, the close proximity of areas with prominent axonal loss and areas containing inflammatory infiltrates (e. g., T cells, macrophages) suggest that axonal damage is closely associated with inflammation. Different soluble or cellular mediators of the immune response have been shown to damage axons in experimental systems, and these may be responsible for neurodegeneration in human disease.

网友[fmuzzy]：

2、MS一定仅累及白质吗？
4、MS除了病灶以外的白质是否是健康的？

MS不仅可累及白质，还可累及灰质（虽然较少出现），但无论是组织病理学还是MRI、MRS都已经证实MS可累及灰质，病变可位于皮层内、近皮层和皮层下深部灰质核团。由于灰质病灶增强后的强化没有白质显著，因而传统的MRI较难发现灰质的病灶，近来有学者使用3D double inversion-recovery MRI可提高灰质病变的检出率。患者灰质的NAA峰值明显低于正常对照，Cho峰值和NAA/磷酸肌酸比值也明显升高;丘脑、尾状核、壳核等深部灰质的NAA峰值也明显降低，尽管其降低幅度明显小于MS患者白质内NAA峰值的降低，反映了灰质内髓鞘成分较少。

Sanfilippo MP, Benedict RHB, Sharma J, Weinstock Guttman B, Bakshi R. The relationship between whole brain volume and disability in multiple sclerosis: a comparison of normalized gray vs. white matter with misclassification correction. Neuroimage 2005;26:1068–1077.
Minagar A. Gray matter involvement in multiple sclerosis: a new window into pathogenesis. J Neuroimaging 2003;13:291–292.
Bakshi R, Ariyaratana S, Benedict RHB, Jacobs L. Fluid-attenuated inversion recovery magnetic resonance imaging detects cortical and juxtacortical multiple sclerosis lesions. Arch Neurol 2001;58:742–748.
Cifelli A, Arridge M, Jezzard P, et al. Thalamic neurodegeneration in multiple sclerosis. Ann Neurol 2002;52:650–653.
Catalaa I, Fulton JC, Zhang X, et al. MR imaging quantitation of gray matter involvement in multiple sclerosis and its correlation with disability measures and neurocognitive testing. AJNR Am J Neuroradiol 1999;20:1613–1618.
Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F. Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 2005;26:572–577.
Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging. Radiology 2005;236:254–260.
Bakshi R, Benedict RHB, Bermel RA, et al. T2 hypointensity in the deep gray matter of patients with multiple sclerosis: a quantitative magnetic resonance imaging study. Arch Neurol 2002;59:62–68.

MS病灶以外白质并非都是健康的。MRS发现MS患者包含病变区的白质，非病变区白质（normal-appearing white matter,NAWM）的NAA/Cr比值均明显低于正常对照组，而非病变区白质和包含病变区的白质间NAA/Cr比值无明显差异；非病变区白质NAA/Cr比值与患者EDSS评分所评估的MS残障程度具有明显相关性，NAA/Cr比值还与MS疲劳程度评分FSS评分呈明显正相关，说明MRS通过检测脑组织代谢物水平的变化可发现MRI不能发现的与MS相关的组织异常，可以作为MS疾病进展早期、敏感的标志物。
Ruiz-Pena JL, Pinero P, Sellers G, et al. Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy. BMC Neurol 2004;4:8.
Narayana PA, Wolinsky JS, Rao SB, He R, Mehta M. PROMiSe Trial MRSI Group. Multicentre proton magnetic resonance spectroscopy imaging of primary progressive multiple sclerosis. Mult Scler 2004;10(suppl 1):S73–S78.
Inglese M, Li BS, Rusinek H, Babb JS, Grossman RI, Gonen O. Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis. Magn Reson Med 2003;50:190–195.

DTI和megnetization transfer技术的原理是什么？

弥散张量成像（diffusiontensorimaging，DTI）是反映水分子随机运动的一种成像方法，可提供关于组织微观结构和排列状态的信息，主要定量指标包括平均弥散率（mean diffusity，MD）反映组织弥散速度和部分各向异性（fractional anisotropy，FA）反映组织内弥散方向。在中枢神经系统,水分子弥散受细胞膜、细胞器和髓鞘等组织微观构筑的影响，凡是能影响组织完整性和排列方向的病变，均可引起MD和FA值的变化。MS的主要病理特点是炎性反应，髓鞘脱失，轴突变性和胶质增生，其中髓鞘脱失和轴突变性均可以严重影响脑组织的完整性和排列方向，从而引起MD和FA值的变化。

磁化传递成像（magnetization transfer imaging，MTI）是基于大分子结合水质子与自由水质子之间存在相互作用，在距水的中心频率1.5Hz附近施加一个饱和脉冲，可以选择性饱和大分子结合的水质子，这种饱和效应被传递到自由水质子，从而降低了MR的信号强度。磁化传递率（MT ratio，MTR）是衡量磁化传递效应的指标，通过在打开和关闭饱和脉冲时分别采集数据，根据公式MTR=(M0-Ms)/M0X100%，计算出MTR值，M0和Ms分别为关闭和打开饱和脉冲时的信号强度，再通过后处理计算出脑内每个体素的MTR，并绘制出磁化传递率直方图（MTR histogram），常用参数有平均MTR峰高及峰位置等。中枢神经系统中自由水质子对应于组织中的水质子，而结合水质子对应于髓鞘和其他细胞膜大分子中的质子，信号丢失的程度取决于给定组织中大分子的密度。因此，MTR降低提示组织内大分子含量的减少，反映了髓鞘的丢失或轴索密度的减少。MS病灶MTR的演变具有规律性，新鲜病灶MTR明显下降，随后的1-6个月逐渐部分或完全恢复正常，其原因在于急性期轴索保存较好，脱髓鞘和水肿引起新鲜病灶MTR下降，而髓鞘再生和水肿消退是MTR随后恢复的病理基础。

附上一幅很漂亮的弥散张量纤维束成像图
A和C为多发性硬化患者，图B和D为正常志愿者，由下图可以看出多发性硬化患者胼胝体纤维较正常志愿者明显稀疏。

网友[风起的时候]：

继发进展型MS定义：
An international panel of experts defined secondary progressive MS as an “initial relapsing remitting disease course followed by progression with or without occasional relapses, minor remissions, and plateaus”.
该型MS的机制目前认为是神经退行性变。
Although there is no consensus on the mechanisms underlying such a transition to the progressive phase, epidemiological and neuroimaging studies indicate that it is probably driven by the high prevalence of neurodegenerative compared with inflammatory pathological changes.
复发-缓解型MS与继发进展型MS的关系：如果前者的病程有足够长，当它变老的时候，就会演变成后者，即后者倾向于是前者的最后结果。
Relapsing–remitting disease can be regarded as multiple sclerosis in which insufficient time has elapsed for the conversion to secondary progression; secondary progressive forms as relapsing–remitting multiple sclerosis that has ‘grown older’; and progressive from onset cases as multiple sclerosis ‘amputated’ from the usual preceding relapsing–remitting phase.
治疗：免疫调节和抑制治疗效果差。
In view of the small effects of immunomodulating and immunosuppressive treatments in preventing the transition to secondary progression, the development of treatments promoting neuroaxonal repair remains an important goal in this disease.

参考文献：
Secondary progressive multiple sclerosis: current knowledge and future challenges
lacet neurology April 2006, Pages 343-354
Natural history of multiple sclerosis: a unifying concept
Brain 2006 129(3):606-616; doi:10.1093/brain/awl007

以下图像是继发进展MS黑洞形成的演示图：没有新病灶，旧病灶没有消失，但是T1像的信号随时间进程稍低一些（最右）。图最左为增强，中为基线图像，右为6个月随访后。