脱髓鞘幻灯2009医大.pptx

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 protecting 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 oligodendrocyte 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 1.Destruction of the myelin sheaths of nerve fibers;fibers;2.Relative sparing of other elements of nervous 2.Relative sparing of other elements of nervous tissue,i.e.of axis cylinders,nerve cell,and tissue,i.e.of axis cylinders,nerve cell,and supporting structure,and a relative lack of supporting structure,and a relative lack of Wallerian,or secondary,degeneration off fiber Wallerian,or secondary,degeneration off fiber tracts.tracts.3.A particular distribution of lesions often is 3.A particular distribution of lesions often is perivenous and primarily in white matter.perivenous and primarily in white matter.Classification of demyelination disease in CNS Dysmyelinative type(leukodystrophy)Dysmyelinative type(leukodystrophy)It It results results from from failure failure to to form form normally normally constituted constituted myelin,myelin,due due to to genetic genetic enzymatic enzymatic disorders,disorders,such such as as adrenoleukodystrophy adrenoleukodystrophy(ADL),(ADL),Globod Globod leucodystrophy leucodystrophy(Krabbe),(Krabbe),Metachromatic Metachromatic leucodystrophy(MLDleucodystrophy(MLD)Demyelinating type Demyelinating typeIt is breakdown of normally constituted myelin.It is breakdown of normally constituted myelin.Classifications of the demyelination diseaseMultiple sclerosisMultiple sclerosis1.1.relapsing-remitting,RR relapsing-remitting,RR 2.primary progressive,PP2.primary progressive,PP3.secondary progressive,SP3.secondary progressive,SP4.progressive relapsing,PR4.progressive relapsing,PRNeuromyelitis optica(Devic)Neuromyelitis optica(Devic)Diffuse Diffuse cerebral cerebral sclerosis sclerosis(Schilder)(Schilder)&concentric concentric sclerosis sclerosis of of Balo Balo Acute disseminated encephalomyelitis Acute disseminated encephalomyelitis Central pontine myelinnolysis 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 occurs 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 pathogenesisEtiology and pathogenesis1 1 1 1.Geographical influenceGeographical influenceGeographical influenceGeographical influence:Populations Populations Populations Populations residing residing residing residing between between between between tropical tropical tropical tropical and and and and subtropical subtropical subtropical subtropical zones zones zones zones have have have have a a a a low low low low risk risk risk risk of of of of MS.MS.MS.MS.All All All All populations populations populations populations residing residing residing residing this this this this latitudes latitudes latitudes latitudes in in in in North North North North America and Europe are higher risk.America and Europe are higher risk.America and Europe are higher risk.America and Europe are higher risk.2.2.Familial factors:Familial factors:Familial factors:Familial factors:It It It It was was was was found found found found that that that that almost almost almost almost 20%20%20%20%of of of of index index index index cases cases cases cases had had had had an an an an affected affected affected affected relative,relative,relative,relative,again again again again with with with with the the the the highest highest highest highest risk risk risk risk in in in in siblings siblings siblings siblings in in in in a a a a large large large large population population population population study study study study in in in in British.British.British.British.studies of twins studies of twins studies of twins studies of twins histocompatibility histocompatibility histocompatibility histocompatibility antigens antigens antigens antigens(HLAs)(HLAs)(HLAs)(HLAs)associations associations associations associations with HLA-A3,B7,B18,and Dw2.with HLA-A3,B7,B18,and Dw2.with HLA-A3,B7,B18,and Dw2.with HLA-A3,B7,B18,and Dw2.Etiology and pathogenesisEtiology and pathogenesis3.3.3.3.Infection and immunological mechanismInfection and immunological mechanismInfection and immunological mechanismInfection and immunological mechanism:immunoregulatory defects may play a critical role in immunoregulatory defects may play a critical role in immunoregulatory defects may play a critical role in immunoregulatory defects may play a critical role in pathophysiology.pathophysiology.pathophysiology.pathophysiology.autoimmunization of T lymphocytes against myelin basic autoimmunization of T lymphocytes against myelin basic autoimmunization of T lymphocytes against myelin basic autoimmunization of T lymphocytes against myelin basic protein protein protein protein caused several different viruses.caused several different viruses.caused several different viruses.caused several different viruses.(Johanson)(Johanson)(Johanson)(Johanson)cellular cellular cellular cellular factors:factors:factors:factors:T T T T lymphocytes lymphocytes lymphocytes lymphocytes regulate regulate regulate regulate humoral humoral humoral humoral immune immune immune immune responses responses responses responses either either either either as as as as potentiators potentiators potentiators potentiators(T-helper(T-helper(T-helper(T-helper cells)cells)cells)cells)or or or or as as as as inhibitors inhibitors inhibitors inhibitors(T-suppressor(T-suppressor(T-suppressor(T-suppressor cells)cells)cells)cells)A A A A reduction reduction reduction reduction in in in in the the the the blood blood blood blood of of of of suppressor suppressor suppressor suppressor T T T T lymphocytes lymphocytes lymphocytes lymphocytes was was was was thought thought thought thought to to to to characterize characterize characterize characterize clinical clinical clinical clinical relapse,relapse,relapse,relapse,or or or or an an an an increase increase increase increase in in in in helper helper helper helper suppressor suppressor suppressor suppressor ratios,ratios,ratios,ratios,(CD4/CD8)(CD4/CD8)(CD4/CD8)(CD4/CD8)dose dose dose dose appear appear appear appear to to to to be be be be associated associated associated associated with with with with increasing disability in patients of MS.increasing disability in patients of MS.increasing disability in patients of MS.increasing disability in patients of MS.Raised Raised Raised Raised titres titres titres titres to to to to many many many many common common common common virusesvirusesvirusesviruses have have have have been been been been found found found found in in in in the the the the serum serum serum serum and and and and CSF CSF CSF CSF of of of of MS MS MS MS patients,patients,patients,patients,but but but but attempts attempts attempts attempts to to to to induce induce induce induce ms experimentally with viruses have been unsuccessful.ms experimentally with viruses have been unsuccessful.ms experimentally with viruses have been unsuccessful.ms experimentally with viruses have been unsuccessful.PathologyPathologyThe Area of demyelination are found in the white matter of the brain and spinal 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 inflammatory infiltrate containing mononuclear cells and lymphocytes is found.Interstitial oedema occurs in acute lesions.Clinical featureEarly symptoms and signsEarly symptoms and signs1.1.Weakness or numbness,sometimes both,in one or Weakness or numbness,sometimes both,in one or more limbs is the initial symptom in about half the more limbs is the initial symptom in about half the patients.patients.2.2.Symptoms Symptoms of of tingling tingling of of the the extremities extremities and and tight tight band-band-like sensations around the trunk are commonly.like sensations around the trunk are commonly.3.3.Visual Visual involvement involvement most most commonly commonly takes takes the the form form of of an an acute acute optic optic neuritis neuritis with with ocular ocular pain.pain.Typically,Typically,there there is is a a central central scotoma.scotoma.In In the the acute acute stages,stages,the the disc disc is is usually usually normal,normal,but but sometimes sometimes it it is is swollen swollen(papillitis)along with peripapillary haemorrhages.(papillitis)along with peripapillary haemorrhages.Early symptoms and signsEarly symptoms and signs4.4.Lhermitte sign was frequent occurrence in MS.Lhermitte sign was frequent occurrence in MS.5.5.Dull,Dull,aching aching pain pain in in the the low low back back is is a a common common plaint.Sharp,Sharp,burning,burning,poorly poorly localized,localized,or or characteristic characteristic lancinating-radicular lancinating-radicular pain,pain,localized localized to to limb limb or or discrete discrete part part of of the the trunk,trunk,occurs occurs but but is is infrequent.infrequent.6.6.Vertigo Vertigo and and diplopia diplopia have have been been a a frequency frequency initial initial sign of brainstem involved in MS.sign of brainstem involved in MS.Other patterns of MS in progressive stage Other patterns of MS in progressive stage The clinical manifestation of MS is protean.The clinical manifestation of MS is protean.Brain stem involvement is common in MS.Brain stem involvement is common in MS.A A unilateral unilateral or or bilateral bilateral internuclear internuclear ophthalmoplegia,ophthalmoplegia,due due to to a a lesion lesion of of the the medial medial longitudinal longitudinal fasciculus,fasciculus,can can occur occur either either as as a a presenting feature,or in established cases.presenting feature,or in established cases.Sixth Sixth nerve nerve palsies,palsies,conjugate conjugate gaze gaze paresis paresis and and the the one-and-a-half one-and-a-half syndrome syndrome are are also also seen.seen.Various Various disorders disorders of of vertical vertical gaze gaze are are described.described.A A vertical vertical skew skew deviation deviation signifies signifies an an intrinsic intrinsic brain brain stem stem or or cerebellar cerebellar lesion lesion(Fig 12.15).(Fig 12.15).Other patterns of MS in progressive stageOther patterns of MS in progressive stage Acute myelitis(transverse myelitis)Acute myelitis(transverse myelitis)Motor symptomsMotor symptoms which which may may begin begin suddenly suddenly or or insidiously,insidiously,include include stiffness,stiffness,difficulty difficulty in in walking walking or or a a tendency tendency to to trip.trip.Clinical Clinical findings findings include include depression depression of of the the abdominal abdominal reflexes,reflexes,lower lower limb limb spasticity spasticity and and extensor extensor plantar plantar responses.responses.Depression Depression of of limb limb reflexes reflexes is is encountered encountered as as is is limb limb wasting,wasting,the the reflection reflection of of an an extensive extensive plaque plaque with with secondary secondary involvement involvement of of the the anterior horn or ventral root exit zoneanterior horn or ventral root exit zone Some patients do show this mental abnormalitySome patients do show this mental abnormality Symptoms of bladder dysfunctionSymptoms of bladder dysfunctionMain patterns of diseases progression for Main patterns of diseases progression for MSMS l l l l Relapsing Relapsing Relapsing Relapsing and and and and remittingremittingremittingremitting with with with with lesions lesions lesions lesions often often often often occurring occurring occurring occurring in in in in different different different different parts parts parts parts of of of of the the the the CNS CNS CNS CNS at at at at different times.different times.different times.different times.l l l l Secondary Secondary Secondary Secondary progressiveprogressiveprogressiveprogressive when when when when the the the the disease disease disease disease starts starts starts starts with with with with a a a a relapsing relapsing relapsing relapsing remitting remitting remitting remitting picture,picture,picture,picture,but but but but recovery recovery recovery recovery from from from from each each each each successive successive successive successive relapse relapse relapse relapse becomes becomes becomes becomes less less less less and and and and less less less less complete,complete,complete,complete,causing causing causing causing residual residual residual residual disability.disability.disability.disability.l l l l Primary Primary Primary Primary progressiveprogressiveprogressiveprogressive in in in in which which which which there there there there is is is is little little little little or or or or no no no no recovery recovery recovery recovery from from from from relapses,relapses,relapses,relapses,with with with with a a a a cumulative cumulative cumulative cumulative disability.disability.disability.disability.Variant of MSNeuromyelitis optica(Devic disease)Diffuse sclerosis or encephalitis periaxialis diffusa(Schilder disease)Concentric sclerosis of BaloDevic diseaseDevic disease视神经脊髓炎（视神经脊髓炎（neuromyelitis optica,NMOneuromyelitis optica,NMO）是一种主要累及视）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，又称神经和脊髓的中枢神经系统炎症脱髓鞘性疾病，又称DevicDevic病或病或DevicDevic综合症，综合症，80%-90%80%-90%的病人可出现复发。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近年来临床、影像学、病理学和免疫学等研究证据提示NMONMO是不同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免疫性疾病 20042004年，年，LennonLennon等人通过间接免疫荧光法检测到等人通过间接免疫荧光法检测到NMONMO病人血清中存病人血清中存在一种特异性自身抗体在一种特异性自身抗体NMO-IgGNMO-IgG，其特异性结合到水通道蛋白，其特异性结合到水通道蛋白4 4（aquaporin-4,AQP4aquaporin-4,AQP4），与），与AQP-4AQP-4发生免疫应答，导致血脑屏障发生免疫应答，导致血脑屏障功能的障碍功能的障碍22。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 MSThe different between NMO and MS 临床上比较临床上比较MSMS病变主要在大脑的脑室周围，临床的复发率要低于病变主要在大脑的脑室周围，临床的复发率要低于NMONMO，视神经和脊髓损害的几率少，即使损害到脊髓也较轻。，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：影像学的区别非常重要：MSMS脑内病灶多见，病灶数量较多，形态学上多数呈现卵圆形、圆脑内病灶多见，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