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多发性硬化一直是学术研究的重点区域之一，原因在于欧美人的MS发病率很高，在老百姓知识的普及度也很大，普通的白种人老百姓一旦听说自己得了MS会大哭起来。我在德国学习的时候，一个我们看来明显是脑卒中的患者最后也做了腰穿，可见德国神经科医生对该病的重视程度。

现提出若干问题如下，学习讨论！
1、MS一定是缓解、复发的病程吗？
2、MS一定仅累及白质吗？
3、MS和视神经脊髓炎还是一种病吗？
4、MS除了病灶以外的白质是否是健康的？
5、MS一定是炎症的过程吗？有无缺血、neurodegeneration的参与？
6、MS的DWI和脑卒中如何鉴别？
7、MS的脊髓病灶和脊髓炎的脊髓病灶有何区别？
8、MS的影像进展实在太多了，最有意义的DTI和megnetization transfer技术的原理是什么?
9、多发性硬化的贝他干扰素治疗仍需解决的问题在哪里？
10、视神经脊髓炎的治疗和普通MS治疗是否相同？

网友[quack008]：

先看看NMO / Devic's disease的来历
In 1870, Sir Thomas Clifford Allbutt first reported an association between myelitis and an optic nerve disorder.disorder. He described a case of myelitis followed by optic nerve changes approximately 3 months later; however,details of his case report are scant and pathology was not presented. Erb published a report of a 52-year-old man who developed recurrent optic neuritis followed by subacute myelitis. The patient partially recovered from his myelopathy but remained with impaired vision.Steffan described a similar patient. Seguin reviewed Erb’s case, one case of the ophthalmologist HD Noyes, and a third personal case of optic neuritis and subacute transverse myelitis. He mistakenly considered the association accidental. Dreschfeld in 1882 described the first pathologically examined case of optic neuritis and myelitis and showed inflammation in both the spinal cord and optic nerves; the brain was normal.Dreschfeld credited Gowers whose classic textbook discloses : In rare cases of myelitis, optic neuritis has been observed, without any intracranial complication to cause it. It is probably not the result of the inflammation of the spinal cord, but is an associated and similar lesion, the result cause of the myelitisymost of the cases thus accompanied have been instances of disseminated myelitisy.Gowers plainly recognized that the optic neuritis and the myelitis were both the result of a common cause.Several additional cases were also described in the 19th century literature. Devic (1858–1930) and his student Gault in 1894 reviewed 16 previously reported similar cases, and Gault studied another case for his doctoral thesis. Gault and Devic believed that cases of optic neuritis and myelitis constituted a distinct clinical entity. Many case reports were later chronicled. Beck reviewed 70 and Stansbury 20 cases but some had pathology in the brainstem and cerebrum more suggestive of ADEM or MS than a discrete entity. （Spinal Cord (2005) 43, 631–634）
F Clifford Albutt had first described this clinical picture in 1870, but Devic coined the term neuromyelitis optica, and Devic’s is the lasting eponymous epithet. （Lancet Neurol. 2005;4(3):136-7. ）

故事读完，回到问题：NMO 和 MS 到底什么关系？

经典教科书说
Standard texts classify the relapsing type (NMO) as a variant of multiple sclerosis. It resembles the optico-spinal variant of MS (OSMS,opticospinal multiple sclerosis).（Spinal Cord (2005) 43, 631–634）

可是有专业人士（代表人物 Mayo Clinic的D.M. Wingerchuk、V.A. Lennon）对此提出异议，认为NMO和MS是两个独立的疾病，列了一堆临床鉴别点，还隆重推出一Biomarker— NMO-IgG

把Devic's syndrome和Devic's disease区分开
Drawing nosological parallels with Parkinson's disease and parkinsonian syndromes, one possibility is to distinguish Devic's syndrome from Devic's disease. Thus a neuromyelitis optica phenotype—Devic's syndrome—occurs in three separate contexts. First, the phenotype is seen in systemic inflammatory or infectious disorders, notoriously systemic lupus erythematosus, but also sarcoidosis, vasculitides, Beh?et's disease, and tuberculosis. Second, (conventional) MS may cause this clinical picture, if the burden of disease falls unevenly on the spinal cord and optic nerves—disseminated lesions do occur elsewhere in the CNS, disclosed by MRI if not clinically eloquent, and CSF contains oligoclonal immunoglobulin bands. Finally, there are patients with neither clinical nor paraclinical evidence of inflammation elsewhere in the CNS or systemically. The diagnosis of Devic's disease should be reserved for these: they show a unique clinical and pathological phenotype clearly separable from MS. （Lancet Neurol. 2005 ;4(3):136-7.）

但具体到Diagnostic Criteria，则争议更大
Spinal Cord (2005) 43, 631–634
Gault and Devic：Retrobulbar neuritis or papillitis accompanied by acute myelitis and occasionally other neurological symptoms or signs not restricted to the spinal cord or optic nerves
-->fail to exclude coexistent myelitis and optic neuritis caused by infection, injury, or tumour, which caused confusion in the early literature.
O’Riordan et al：
1. a severe transverse myelitis;
2. an acute unilateral or bilateral optic neuropathy;
3. no clinical involvement beyond the spinal cord or optic nerves; and
4. a monophasic or multiphasic illness.
-->allow for polyphasic and unilateral optic neuritis cases but require the myelitis to be both rapid and transverse.
NEUROLOGY 2006;66:1485–1489
Wingerchuk et al：
Definite NMO
Optic neuritis
Acute myelitis
At least two of three supportive criteria
1. Contiguous spinal cord MRI lesion extending over >=3 vertebral segments
2. Brain MRI not meeting diagnostic criteria for multiple sclerosis
3. NMO-IgG seropositive status

看看挑战传统的专业人士到底为什么认为NMO和MS是两回事
Comparison of neuromyelitis optica and multiple scelorosis（Lancet 2003; 361:889-890）

还有There is evidence associating HLA-DRB1-1501 with MS in contrast to NMO associated with DRB1-802, DPB1 501, but this indicates susceptibility rather than cause.（Spinal Cord (2005) 43, 631–634）

另一篇是前面已广告过的NMO-IgG
NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin.Sensitivity and specificity were 73% (95% CI 60–86) and 91% (79–100) for neuromyelitis optica and 58% (30–86) and 100% (66–100) for optic-spinal multiple sclerosis.（Lancet 2004; 364: 2106–12）
NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy. （ J Exp Med. 2005;202(4):473-7）

当然总会有捍卫传统者跳出来，使问题进一步复杂化，讨论焦点成了"OSMS到底是不是MS的一种？"，使“百花齐放”放到白热化程度，导火索正是NMO-IgG
Lennon推出NMO-IgG时如此Interpretation ：NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the bloodbrain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.（Lancet 2004; 364: 2106–12）
Japan OSMS多，带着点讥讽 " “OSMS is NMO, but not MS”: confirmed by NMO-IgG?"（Lancet Neurol. 2005;4(10):594-5.）
Wingerchuk语气强硬争锋相对"OSMS is NMO, but not MS: proven clinically and pathologically"（Lancet Neurol. 2006;5(2):110-1. ）
NMO 、OSMS 、MS，每两者之间的关系都受到了质疑

This distinction is important prognostically and therapeutically because optimal treatments differ for NMO (immunosuppression) and MS (immunomodulation with beta-IFN or glatiramer acetate).（J Exp Med. 2005;202(4):473-7）

结论：
The relation of Devic's disease to multiple scelrosis (MS) is complex and not entirely resolved.（Lancet Neurol. 2005 Mar;4(3):136-7.）
Whether NMO is a distinct disease or part of the wide spectrum of multiple sclerosis is debated.
It is clear that many conditions are associated with, or result in, NMO. Separation from classical and variant MS, and variant forms of disseminated encephalomyelitis,has been widely attempted, but no incontrovertible diagnostic features have been proved. Despite reported differences, it remains likely that these conditions are part of the same spectrum of inflammatory demyelination in which the genetic background and immune factors define the pattern of disease.
The terms NMO and Devic’s syndrome retain utility and convenience for reference until the syndrome is broken down into its composite aetiologies.（Spinal Cord (2005) 43, 631–634）

一个很精彩的文献回顾，这个问题结合第10问在本次讨论中可以close了。
尽管在当前研究中还没有close，但是对于中国这个NMO相对高发的国度，大家应该注意到该领域的进展。NMO不论出于那个国界，这个实体是存在的。

我们能够实际应用到的东西是：NMO的治疗激素的减量倾向于要保守，甚至长期使用，维持量也较大，而在MS，激素不是减少复发的必然因素，可以快速减量，用贝他干扰素预防复发。
Practical Neurology 2006;6:180-184; doi:10.1136/jnnp.2006.091850
MANAGEMENT OF RELAPSES

High dose corticosteroids and supportive care remain the mainstays of management of relapse. In view of the severity of relapses and likely need for maintenance treatment our policy is to follow a course of intravenous methylprednisolone (1 gram daily for 3–5 days) with a gradual taper of oral prednisolone over several months, from an initial dose of 1 mg/kg/day. An alternate day maintenance dose of the order of 10–20 mg prednisolone is generally our target in patients with relapsing disease.

A minority of patients fail to respond to adequate steroid therapy or relapse rapidly and in such cases there is a role for therapeutic plasma exchange. We consider it early—within weeks of symptom onset. In the North American randomised trial of plasma exchange in severe demyelinating events, patients with neuromyelitis optica were overrepresented among the responders, with a 60% response rate (versus 6% overall for sham exchange). In this study plasma exchange was undertaken within three months of onset of relapse.

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7、MS的脊髓病灶和脊髓炎的脊髓病灶有何区别？
答：MS的脊髓病灶一般为斑点状不规则TI低信号及T2高信号斑块。大多数矢状位长度小于2 个椎体， 病变长度大于宽度，病变局部脊髓正常或轻度肿胀。横断面上病变位于脊髓周边，面积多小于脊髓断面的一半，病变在急性或活动期可有强化。颈段脊髓是相对常见的部位。
注：周边的意思就是白质为主。

脊髓炎：T1WI 为低信号或等信号，T2WI 呈明显的高信号，较均匀，变累及范围常较大，一般2 个椎体高度以上，以下颈部及胸段脊髓常见，慢性期可出现脊髓萎缩。常见于累及脊髓的中央，可横贯，意及灰质。