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1、Demyelinating disease of the CNS 中枢神经系统脱髓鞘疾病,Tianjin medical University General hospital Zhou Guang xi 天津医科大学总医院神经内科 周广喜 7702,Overview,Demyelinative disease is a group of diseases of brain and spinal cord in which destruction of myelin is a prominent feature. Myelin sheaths play importance role in p
2、rotecting and supporting for nervous fiber and transporting of material to neurons and maintaining of neurons ionic environment. The formation of myelin sheaths in both the central and peripheral nervous system follows a similar pattern. Central myelin is formed by an extension of membrane of the ol
3、igodendrocyte wrapping the axons, whereas peripheral myelin is formed by the extension of the Schwann cell membrane.,The commonest accepted the pathologic criteria of demyelinative disease in CNS:,1. Destruction of the myelin sheaths of nerve fibers; 2. Relative sparing of other elements of nervous
4、tissue, i.e. of axis cylinders, nerve cell, and supporting structure, and a relative lack of Wallerian, or secondary, degeneration off fiber tracts. 3. A particular distribution of lesions often is perivenous and primarily in white matter.,Classification of demyelination disease in CNS,Dysmyelinativ
5、e type (leukodystrophy) It results from failure to form normally constituted myelin, due to genetic enzymatic disorders, such as adrenoleukodystrophy (ADL), Globod leucodystrophy (Krabbe), Metachromatic leucodystrophy (MLD) Demyelinating type It is breakdown of normally constituted myelin.,Classific
6、ations of the demyelination disease,Multiple sclerosis 1. relapsing-remitting , RR 2. primary progressive, PP 3. secondary progressive, SP 4. progressive relapsing , PR Neuromyelitis optica (Devic) Diffuse cerebral sclerosis (Schilder) & concentric sclerosis of Balo Acute disseminated encephalomyeli
7、tis Central pontine myelinnolysis,Multiple sclerosis,Multiple sclerosis is the most common demyelinating disorder. It is a disease of the central white matter with “ lesions separated in time and space”. Generally, MS is characterized clinically by remitting - relapsing course. The disease usually o
8、ccurs in young adults. The peak age of onset is 20-40 and 95% patients occurs between 10-60 years. More females than males are affected.,Etiology and pathogenesis,1. Geographical influence: Populations residing between tropical and subtropical zones have a low risk of MS. All populations residing th
9、is latitudes in North America and Europe are higher risk. 2. Familial factors: It was found that almost 20% of index cases had an affected relative, again with the highest risk in siblings in a large population study in British. studies of twins histocompatibility antigens (HLAs) associations with H
10、LA- A3, B7, B18, and Dw2.,Etiology and pathogenesis,3. Infection and immunological mechanism: immunoregulatory defects may play a critical role in pathophysiology. autoimmunization of T lymphocytes against myelin basic protein caused several different viruses. (Johanson) cellular factors: T lymphocy
11、tes regulate humoral immune responses either as potentiators (T-helper cells) or as inhibitors (T-suppressor cells) A reduction in the blood of suppressor T lymphocytes was thought to characterize clinical relapse, or an increase in helper suppressor ratios, (CD4/CD8) dose appear to be associated wi
12、th increasing disability in patients of MS. Raised titres to many common viruses have been found in the serum and CSF of MS patients, but attempts to induce ms experimentally with viruses have been unsuccessful.,Pathology,The Area of demyelination are found in the white matter of the brain and spina
13、l cord. The lesions may vary in diameter from less than a millimeter to several centimeters. The periventricular localization is characteristic. Other favored structures are the optic nerves and chiasm, brainstem and cervical cord. There is myelin destruction with relative preservation of axons. An
14、inflammatory infiltrate containing mononuclear cells and lymphocytes is found. Interstitial oedema occurs in acute lesions.,Clinical feature,Early symptoms and signs Weakness or numbness, sometimes both, in one or more limbs is the initial symptom in about half the patients. Symptoms of tingling of
15、the extremities and tight band-like sensations around the trunk are commonly. Visual involvement most commonly takes the form of an acute optic neuritis with ocular pain. Typically, there is a central scotoma. In the acute stages, the disc is usually normal, but sometimes it is swollen (papillitis)
16、along with peripapillary haemorrhages.,Early symptoms and signs,Lhermitte sign was frequent occurrence in MS. Dull, aching pain in the low back is a common complaint. Sharp, burning, poorly localized, or characteristic lancinating-radicular pain, localized to limb or discrete part of the trunk, occu
17、rs but is infrequent. Vertigo and diplopia have been a frequency initial sign of brainstem involved in MS.,Other patterns of MS in progressive stage,The clinical manifestation of MS is protean. Brain stem involvement is common in MS. A unilateral or bilateral internuclear ophthalmoplegia, due to a l
18、esion of the medial longitudinal fasciculus, can occur either as a presenting feature, or in established cases . Sixth nerve palsies, conjugate gaze paresis and the one-and-a-half syndrome are also seen. Various disorders of vertical gaze are described. A vertical skew deviation signifies an intrins
19、ic brain stem or cerebellar lesion (Fig 12.15).,Other patterns of MS in progressive stage,Acute myelitis (transverse myelitis) Motor symptoms which may begin suddenly or insidiously, include stiffness, difficulty in walking or a tendency to trip. Clinical findings include depression of the abdominal
20、 reflexes, lower limb spasticity and extensor plantar responses. Depression of limb reflexes is encountered as is limb wasting, the reflection of an extensive plaque with secondary involvement of the anterior horn or ventral root exit zone Some patients do show this mental abnormality Symptoms of bl
21、adder dysfunction,Main patterns of diseases progression for MS,l Relapsing and remitting with lesions often occurring in different parts of the CNS at different times. l Secondary progressive when the disease starts with a relapsing remitting picture, but recovery from each successive relapse become
22、s less and less complete, causing residual disability. l Primary progressive in which there is little or no recovery from relapses, with a cumulative disability.,Variant of MS,Neuromyelitis optica ( Devic disease) Diffuse sclerosis or encephalitis periaxialis diffusa ( Schilder disease) Concentric s
23、clerosis of Balo,Devic disease,视神经脊髓炎（neuromyelitis optica,NMO）是一种主要累及视神经和脊髓的中枢神经系统炎症脱髓鞘性疾病，又称Devic病或Devic综合症，80%-90%的病人可出现复发。 近年来临床、影像学、病理学和免疫学等研究证据提示NMO是不同于多发性硬化的一类具有独特免疫病理学机制及临床特征的自身免疫性疾病 2004年，Lennon等人通过间接免疫荧光法检测到NMO病人血清中存在一种特异性自身抗体NMO-IgG，其特异性结合到水通道蛋白4（aquaporin-4,AQP4），与AQP-4发生免疫应答，导致血脑屏障功能的障碍
24、2。 其病理学表现为累及脊髓白质和灰质的病灶，受累脊髓肿胀、软化，出现广泛的脱髓鞘，并有空洞、坏死以及急性轴索损害；典型病灶位于脊髓中央，少突胶质细胞丢失明显较少髓鞘再生,The different between NMO and MS,临床上比较MS病变主要在大脑的脑室周围，临床的复发率要低于NMO，视神经和脊髓损害的几率少，即使损害到脊髓也较轻。 影像学的区别非常重要： MS脑内病灶多见，病灶数量较多，形态学上多数呈现卵圆形、圆形或垂直朝向脑室的病灶，脊髓MRI病灶较小，多局限在一个脊椎节段，轴位上显示病灶局限，多位于脊髓髓内偏外侧； NMO也可出现颅内病灶，但相对不典型，多累及皮层下白质
25、、胼胝体、脑干及下丘脑等部位，这些病灶数量较少，呈现大片状不规整形状，脊髓病灶较大，其长度多大于三个脊椎节段，位于脊髓中央位置。 NMO患者CSF水通道蛋白4抗体阳性 。,Concentric sclerosis of Balo,Laboratory findings,CSF: mononuclear pleocytosis ( usually 50 cells /cm). protein content is increased slightly. IgG is increased. Oligoclonal bands (OB )is found Evoked potentials abno
26、rmal: these include visual, auditory and somatosensory evoked responses. CT scanning can demonstrate abnormalities single . MRI has proved of immense value T2-weighted images are particularly useful for demonstrating lesions in the periventricular region. The technique allows demonstration of lesion
27、s of the brain stem and in the spinal cord. enhancement has been used to assess the activity of any abnormal signal area.,Diagnosis (Poser 1983),NMSS诊断标准 (2001),Differential diagnosis,1. Acute disseminated encephalomyelitis, (ADEM) It is an acute illness with scattered small demyelinative lesions, b
28、ut it is self-limited and monophasic. Pathologically, perivascular areas of demyelination are scattered throughout the brain and spinal cord, with an associated inflammatory reaction. A similar disorder may also occur independently, with no apparent infection; it may then represent the initial manif
29、estation of multiple sclerosis. Furthermore, fever, stupor, and coma, which are characteristic, rarely occur in MS.,Differential diagnosis,2.systemic lupus erythematosus and other autoimmune disease. there may be multiple lesions of CNS white matter. Close attention to the characteristic history (ra
30、sh and arthritis etc.) and serologic findings should permit the distinction of the two diseases. 3. Cervical spondylosis The typical protein abnormalities of MS is absent. The disturbance of bladder function occur late or not at all in it. 4. Behcet disease are recurrent iridocyclitis and meningitis
31、 , mucous membrane ulcer of mouth and genitalia , and symptoms of articular. renal, lung and multifocal cerebral disease.,Treatment,Corticosteroids: Methylprednisolone is 500 to 1000 mg daily for 3-5 days, iv., followed by high oral doses of prednison 60 mg daily and tapering this dosage over a 12 d
32、ay is generally effective and 5-10/week. Immune globulin (IG) iv 0.4/kg /d 3-5 days. Beta-Interferon 1-a and 1-b: (30ug or 6.6 million unit im/weekly) and Copolymer 1 (Glatiramer acetate) (20mg/daily, subcutaneous) Suppression of the immune system: Azathioprine or cyclophosphamide . Plasmapheresis Symptomatic treatment: spasticity Baclofen; painful Tegretal ; Intention tremor Clonazepam; tiredness Amantadine,问答题,简述脑炎主要临床表现（脑炎的共性表现）？ 中枢神经系统脱髓鞘疾病的药物治疗？,