中枢神经系统疾病(英文)

1、Disease of Central Nervous System 1The nervous system（神经系统）central nervous system(CNS) brain spinal cordperipheral nervous system(PNS) 22Disease of CNS IntroductionBasic pathological changes Neurodegenerative disease : AD ; PD.Common complicationsHemodynamic Derangement & Cerebral Vascular Disorders

2、TumorInfection disease331.Delicate structure, more than 50% human genes are neuronal related： structure or metabolism ; complex or arcaneIntroduction : Disease of CNS442. Lesions may have location indication ( selective dysfunction) signal to and from different regions of the body are controlled by

3、very specific areas within the nervous system nervous system vulnerable to focal lesions Introduction : Disease of CNS553.Dual influences of some structures such as skull and dura, protection of brain and may facilitate increased intra-cranial pressure.66Introduction : Disease of CNS4. Special disea

4、se :degenerative disease demyelination disease psychiatric diseases less understandingCongenital anomalies: high incidence77Cells in CNS Neuron glia cells astrocyte oligodendrocyte microglial cellsBasic pathological changes of cells in CNSNeuropil: process of the cells in the CNS to form a delicate

5、fibrillary background 8Basic Changes of Cells Neuron（神经元）99Basic Changes of Cells Neuron（神经元）1.Central Chromatolysis (中央性尼氏小体溶解) Cause： axonal injury, Viral infection, deficiency of Vit.B, anoxia. Morphology: Sequalae: In early stage, increased dissociated ribosome from RER may facilitate protein sy

6、nthesis. The change would be reversible, if cause abolished. Insistent change may lead to neuronal death. Normal Neuron Central Chromatolysis10101. 尼氏体 (Nissl bodies) rough endoplasmic reticulum (RER)Basic Changes of Cells Neuron（神经元）11112.Ischemic Changes （Acute Necrosis） Cause：ischemia, anoxia, hy

7、poglucemia, lower blood pressure, epilepsy Morphology：vacuolation, red neuron, ghost cell Basic Changes of Cells Neuron VacuolationRed Neuron1212Basic Changes of Cells Neuron 3. Neurophagia(嗜神经元现象） dead neuron engulfed and phagocytosed by M.13134. Inclusion Bodies (包涵体) viral infections; neurodegene

8、rative disease (1) Rabies: Negri body diagnostic hallmark of rabies HSV; Encephalitis B Jap.virus; Poliovirus Basic Changes of Cells Neuron Negri Body14144. Inclusion Bodies (包涵体) Parkinson Dis.： Lewy bodyMuhammao Ali Substantia nigraBasic Changes of Cells Neuron 1515Neurodegenerative changes : SP,

9、NFTsSenile Plaque (SP , 老年斑)： the core composed with -amyloid protein, surrounded by a halo and swollen degenerative axons Basic Changes of Cells Neuron 4. Inclusion Bodies (包涵体)1616神经原纤维（neurofibril）Normal structure 1717Neurofibrillary Tangle (NFTs, 神经原纤维缠结):the tangle composed by double spiral str

10、ands of neurofibils with abnormal phosphorylated tau protein marker of dying neuron seen in Alzheimers Dis., boxer brain, post-encephalitis, ParkinsonismBasic Changes of Cells Neuron 4. Inclusion Bodies (包涵体)HESliver impregnation1818Senile PlaqueNeurofibrillary Tangle Alzheimers disease ADHigh densi

11、ty and widespread distribution of plaques and tangles in the neocortical areas in the setting of dementia that allows one to make a diagnosis of AD19195. Wallerian Degeneration (华勒变性） usually occur in traumatic transfection of a nerveBasic Changes of Cells Neuron 2020Immunofluorescence Anti glial fi

12、brillary acid protein (GFAP)Astrocyte are the major supporting cells in the brainBasic Changes of Cells astrocyte HE staining: naked nucleiSliver impregnation2121Basic Changes of Cells AstrocyteHypertrophy： The cytoplasm is shown with HE stain. The processes elongate The cell and its nuclear are enl

13、arged with binuclei, multinuclei or bizarre nucleiProliferation ：reactive astrogliosis: repair process after insults forming glial scar. Seen in local area of anoxia, edema, infarct and at the periphery of abscess or tumor. 2222Basic Changes of Cells AstrocyteRosenthal fiberHE: a thick, elongated, w

14、orm-like or corkscrew eosinophilic (pink) bundle that is found on H&E staining of the brain The fibers are found in astrocytic processes and are thought to be clumped intermediate filament proteins(GFAP).long standing gliosis, occasional tumors(pilocytic astrocytoma), and some metabolic disorders (A

15、lexanders disease).pilocytic astrocytoma23Corpora amylacea(淀粉样小体）: increased with aging glycoprotein-rich material located at the end process of astrocytes , especially in the subpil and perivascular zonesBasic Changes of Cells -Astrocyte 2324Basic Changes of Cells Oligodendrocyte (少突胶质细胞 )Myelin fo

16、rmation cells in CNS (in PNS: Schwann cellsHE staining: in size and shape like lymphocyteLeucodystrophy (白质营养不良) myelin sheath formation disturbance different congenital enzyme deficiencyDemyelination (脱髓鞘病变) formed myelin sheath destroyed due to allergy, anoxia or toxificationPerivascular demyelina

17、tion(Luxol fast blue staining )2425Progressive multifocal leukocephalopathy( PML)Demyelinating diseaseThe cause of PML is a type of polyomavirus called the JC virus (JCV)Severe immune deficiency, such as transplant patients on immunosuppressive medications, patients receiving certain kinds of chemot

18、herapy or AIDS patients( 5%)Basic Changes of Cells Oligodendrocyte (少突胶质细胞 )intranuclear inclusions PML destroys oligodendrocytes ; produces intranuclear inclusions26Microglia (小胶质细胞） Resting microglia may activated and turn into M (1) Focal proliferation forming microglial nodule (2) Rodlike microg

19、lia seen in advanced syphilis2527Gitter cell/foam cells2628Microglial nodule rod cells2729 normally line the ventricular cavities and the central canal of the spinal cord Oncogenesis, Deficiency after injury may repaired by astrocyte, forming so called granular ependymitis (颗粒性室管膜炎)Basic Changes of

20、Cells Ependymal cells (室管膜细胞)2830Common Complications脑水肿 （Brain Edema)脑积水（ hydroceplus)颅内压升高及脑疝（ herniation)2031Common Complications脑水肿 （Brain Edema)Increased water contents within brain parenchymaCause: anoxia, infarction, inflammation, injury, toxification and tumor.Mechanism : 1. Vasogenic: disru

21、pted normal BBB interstitial edema white mattergray matter 2. Cytotoxic: cytomembranous pump (ATPase) intracellular edema white matter=gray matter usually mixed type32EdemaMorphology: brain volume, weight, narrow sulci, widened gyri, cutting surface showed small ventricle, increased reflection. Hern

22、iation may ensure.33Common complications Hydrocephalus （脑积水) Accumulation of excessive CSF with ventricular dilatation as a result of a disturbance of its secretion, circulation and absorption CSF: cerebrospinal fluid34Three layers of the meningesdura mater leptomeningesthe arachnoid mater(arachnoid

23、 villi) the subarachnoid space(CSF) the pia Circulation of CSF Choroids plexusventricular systemarachnoid villiThe rate of formation and absorption of CSF remain in balanceFunction: act as the lymphocytic drainage in the brain35Over-secretion of CSF(tumor of choroid plexus) Absorption disturbances o

24、f CSFNoncomunicating (obstructive)： tumor, inflammatory, adhesion, hemorrhage, or deformity in III ventricle.2) Communicating : meningitis, subarachnoid hemorrhage, with subsequent organization, or causing scarring of arachnoid granulation or Villi.Cause & Pathogenesis36Morphology: Dilation of ventr

25、icles with atrophy of parenchyma of brain,due to compression of CSF.CPC: headache, vomiting, papilloedema of optic N.Common complications Hydrocephalus （脑积水) 37Common complicationHypertension of intracranial pressure(ICP) and Herniation (颅内压升高和脑疝形成）The CSF pressure more than 2kPa( normally 0.6-1.8 k

26、Pa) with lateral recumbent position 38Cause：（1）cerebral edema, hydrocephalus（2）occupying lesion: tumor, hemorrhage, hematoma（3）inflammation: meningitis, cerebral abscess, encephalitis（4）brain infarctionThe factors influence the results:（1）the size of the lesion and its development rapidity.（2）existe

27、d cranial cavity situationsenile atrophy or unclosure of fontanelle allowing more space for expending of brainCommon complications Hypertension of ICP & Herniation39Sequalae： （1）headache, vomiting, papilloedema, coma, death Common complications Hypertension of ICP & Herniation402) Herniation: displa

28、cement of brain tissue from one intracranial component into another , or into the spinal canal 1. Subfalcine (cingulate gyrus) herniation 2. Transtentorial (uncinate gyrus) herniation 3. Tonsillar herniation 4. External cerebral herniation41Subfalcine (cingulate gyrus) herniation： local tissue hemor

29、rhagic and necrotic, weakness and sensory dysfunction of legAnterior cerebral artery422. Transtentorial (uncinate gyrus) herniation：432. Transtentorial (uncinate gyrus) herniation：ipsilateral III N compressed leading to pupils constricted dilated “blown pupil”III oculomotor nerve 443.Transtentorial

30、(uncal gyrus) herniation：Kernohan切迹paralysis of ipsilateral extremities (false localization sign)the cerebral pedunclethe corticospinal tractthe corticospinal tractKernohans notch 45Transtentorial (uncal gyrus) herniation：periaquaductal hemorrhage tearing of penetrating V. A. 46Hypertension of ICP &

31、 HerniationTonsillar herniation, life-threatening press respiration centers in medulla oblongata sudden death virtal respiratory and cardic centers in the medullaforamen magnum47Hemodynamic Derangement & Cerebral Vascular Disorders48Hemodynamic Derangement & Cerebral Vascular DisordersCirculation di

32、sturbances: ischemic encephalopathy infarction( thrombotic or embolitic) hemorrhageVascular disorders: arteriolosclerosis, atherosclerosis, arteritis, aneurysm, ateriovenous malformation(AVM)49widespread ischemia/hypoxia injury occurs due to a generalized reduction of cerebral perfusion caused by hy

33、pertension, cardiac arrest, hemorrhage and shock. the brain :1%2% of body weight oxygen consumption about 20%systolic pressure less than 50mmHg will cause severe brain injuryHemodynamic Derangement & Cerebral Vascular Disorders global cerebral ischemia/ischemic Encephalopathy50Predisposing factors：h

34、igher metabolic rate：more susceptible NeuronAsOligoEndo Gray MatterWhite Matter 3rd、5th、6th layers of cortex are most vulnerable Persistence and severity of ischemia mild ischemia: no remarkable change severe ischemia, survive few hours before death: not remarkable moderate ischemia, survive more th

35、an 12 hours：typical changesArchitecture of cerebral arteries the location at the border zone of cerebral arteries is much more vulnerable.51Border zone of cortex C shape Architecture of Cerebral Arteries52Changes:laminar cortical necrosis : neurons in 3rd, 5th, 6th layers of cortex involvedhippocamp

36、us sclerosis ：pyramidal neuron deathborder zone infarction ： early stage： “C” shaped infarct later stage: astrogliosis (granular atrophy) cardiopetal developmentglobal necrosis(respirator brain) Hemodynamic Derangement & Cerebral Vascular DisordersIschemic Encephalopathy53Laminar Cortical NecrosisHe

37、modynamic Derangement & Cerebral Vascular DisordersIschemic Encephalopathy54Fresh border zone infarctGranular atrophy(gliosis)Cutting surface of granular atrophyRespirator brainHemodynamic Derangement & Cerebral Vascular DisordersIschemic Encephalopathy55CPC：weakness sensation abnormalities coma, pe

38、rsistent vegetative state death clinical criteria for brain death respirator brain: autolytic process brown discoloration and unfixed brainperson in a vegetative state/ vegetable can wake up?56Hemodynamic Derangement & Cerebral Vascular DisordersFocal Cerebral Ischemia57Cause： thrombosis, embolism,

39、space occupying lesion, local vessels compressed by herniationTypes: thrombotic: on the sites of atherosclerosis inner carotid A,basilar A, cerebral arteries, The symptoms: insidious and gradual development from weakness of muscles to semiplegia or comaembolic: the emboli often are cardiogenic , or

40、from atherosclerotic plaque, with sudden onset and poor prognosis.Hemodynamic Derangement & Cerebral Vascular DisordersCerebral Infarction58The most common form of cerebrovascular disease, accounting for 70%80% of all cerebral vascular accidents “stroke”Changes: extent of ischemia: Occlusion in inne

41、r carotid artery: circle willis may compensate completely, no infarctionOcclusion in mid-size artery: as middle cerebral A, the infarct smaller than its supply area due to partial anastomosis.Occlusion in terminal arteries: leading to supplied area infraction.Hemodynamic Derangement & Cerebral Vascu

42、lar DisordersCerebral Infarction59Types: white infarctred infarct: incomplete occlusion or frangible emboli going further to small vessels, resulting in blood escape from injured vascular wall.Morphology changes: first 412h: normal then: ischemic neuronal changes 36-48h: swollen and soft; demarcatio

43、n between gray and white matter becomes blurred due to edema the third day: macrophage, progressive marked demarcation of the lesion 1 month: liquefaction, irregular cavities 6 month: completely liquefied with gliosis( scar) 60Pathological changes ischemic neuronal changesliquefaction, irregular cav

44、itiesreactive gliosis61Two important terms of Brain infarction Lacunae(腔隙性梗死）: sharply defined necrosis less than 1.5cm in diameter, corresponding to the territory of a single perforating artery, the main cause of lacunae was considered to be hypertension62Two important terms of Brain infarction Lac

45、unae(腔隙性梗死）: sharply defined necrosis less than 1.5cm in diameter, corresponding to the territory of a single perforating artery, the main cause of lacunae was considered to be hypertensionTIAs( transient ischemic attacks 一过性脑缺血) transient episode of neurologic dysfunction lasting several minutes24

46、hours an important predictor of subsequent infarcts 1/3 patients with TIA developing clinically significant infarcts within 5 years 63Infarction area supplied by middle cerebral A.64Hemodynamic Derangement & Cerebral Vascular DisordersBrain HemorrhageIntracerebral HemorrhageCause: hypertension * con

47、genital saccular aneurysms, tumors, hemorrhagic diathesis, vasculitis, AVM, trauma Hypertension accounts for about half of Spontaneous brain hemorrhage Pathogenesis:anoxia of vascular wallanoxia of perivascular tissue Charcot Bouchard microaneurysmsmicro-softening focivessels rupturedspasm of vessel

48、s B.P hemorrhage65Occur in small blood vessels (less than 300 micrometre diameter)Often located in the lenticulostriate vessels of the basal ganglia and are associated with chronic hypertension A common cause of stroke Charcot Bouchard microaneurysms66Common locations: the putamen, caudate, thalamus

49、, pons, and cerebellum.Changes: In the center of foci, normal structure is destroyed and filled with RBC，at periphery multifoci of hemorrhage The old hemorrhage foci becomes cavitated & with hemosiderin.Hemodynamic Derangement & Cerebral Vascular DisordersBrain HemorrhageHypertensive Hemorrhages67Ce

50、rebral Hemorrhage68CPC：B.G hemorrhage:directed to insular contralateral semiplegia directed to ventricle , thalamus deathPons hemorrhage: pin-like pupils, persistent high fever or sudden deathCerebellar hemorrhage: severe occipital headache, frequent vomitingHemodynamic Derangement & Cerebral Vascul

51、ar DisordersBrain Hemorrhage69Subarachnoid hemorrhageThe most common cause of spontaneous(nontraumatic) Rupture of a saccular(berry) aneurysm approximately 1% of the general population different from the fusiform dialtion in atheroslcerosis or infectious (mycotic) aneurysm 80% arise at the arterial

52、bifurcations in the territory of the internal carotid artery: MCA, ACMDeveloped the infarct of brain parenchyma70CPC: Abrupt, severe headache, vomitting, loss of consciousness Meningeal signs Bloody CSF 50% died in several days acute hydrocephalus herniation brain infarction chronic: hydrocephalus71

53、Vascular malformationAbnormalities in angiogenesis in the developing brain AVM: the most common caused vessels of variable caliber including A,V Hemorrhagic, calcification, reactive gliosis72Etiology: the disease cause by living pathogens, which are infective , endemic in certain geographic areas an

54、d in certain seasons (传染性，流行性，地方性，季节性）Unique route of invasion, a given pathogen has :unique entrance of invasionunique mode of spreading among hostunique affinity for special tissue or organs , causing special pathological changesPathogenesis bacteria: endotoxin and /or exotoxin viruses: cellular a

55、nd /or humoral immunityInfectious DiseaseCommon Features(共同特性）73Basic pathologic changes: inflammation( acute/chronic) depending on host pathogen host: immunity pathogen: invasion ability, toxins, metabolic substance evocation of allergic reaction of hostClinical course Incubation period: Pre drome

56、period: non specific symptoms and signs Dominant period: diagnostic symptoms and signs peak Recovery period: the disease subsides typical/atypical/subclinical courseInfectious DiseaseCommon Features(共同特性）免疫性74ConsequencesComplete recovery the host gains temporary or permanent immunityChronic courseR

57、ecurrence of diseaseDeathInfectious DiseaseCommon Features(共同特性）75Infectious DiseaseCommon Features in CNS(共同特性）SkullMeninges dura 硬脑膜 arachnoid 蛛网膜 pia 软脑膜 BBB effectively protected CNS from the infective agents Pre-existing immunodeficiency conditions Special virulence factors of pathogens Host de

58、fense mechanism are suboptimal to control pathogen infection in CNSleptomenige （软脑膜）Page 41076Route of infectionHematogenic: septicema, viremiaLocal disseminated: opened skull fracture, sinusitis, mastoiditisDirect infected: trauma, iatrogenic interference (lumbar puncture)Through peripheral nervous

59、 system: rabies, HSVInfectious DiseaseCommon Features in CNS(共同特性）77Inflammation featureStereotyped Reaction neurons: degeneration, necrosis secondary demyelination limited exudation with perivascular cuffing formation Presence of BBB (blood brain barrier) and V-R space limits the spread of inflamma

60、tion Absence of intrinsic lymphatic and lymphoid tissue T/B cells are blood born(exogenic)glia nodule formation microglial nodule in early stage. astrocytic nodule in later stage, repair78Components Endothelial cellsBasal membranepericyteAstrocytic feet 血脑屏障（Blood-Brain Barrier, BBB）Functions protec