Diseases of the Nervous System

Diseases of the Nervous System

Kun Mu （牟坤） MD, PhD

Department of Pathology

School of Medicine, Shandong University

Contents

Structure of the NS and basic pathologic changes Common complications of CNS Infectious diseases of NS Neoplasms of NS

I. Structure of the CNS and basic pathologic changes

Cerebellum( 小脑 )

Cerebellar peduncles( 小脑脚 )

Occipital lobe( 枕叶 )

Gyri( 脑回 ) Sulci( 脑沟 ) Parietal lobe( 顶叶 )

Frontal lobe( 额叶 )

Pons( 桥脑）

Fourth ventricle( 四脑室 )

Spinal Cord ( 脊髓 )

Microscopic structure of the CNS

Neuron （神经元） Cell bodies-- grey matter Cell processes– axons--White matter bundles

Staining of neurones in the cerebral cortex


Neuron （神经元） Cell bodies-- grey matter Cell processes– axons--White matter bundles Glia （胶质细胞） Astrocytes Oligodendrocytes Ependymal cells

Staining of astrocyte in the cerebral cortex

Glia-oligodendrocytes

Ependymal cells


Neuron （神经元） Cell bodies-- grey matter Cell processes– axons--White matter bundles Glia （胶质细胞） Astrocytes Oligodendrocytes Ependymal cells Microglia （小胶质细胞） Meningocyte （脑膜细胞） Vessel （血管）

I. Basic pathology changes of CNS

Neuron Astrocytes Oligodendrocytes Ependymal cells Microglia

1. Basic pathology changes of the Neuron

Chromatolysis （尼氏体溶解） Red neuron （红色神经元） Simple neuronal atrophy （单纯性神经元萎缩） Cellular inclusion （包含体形成） Cell Structure protein change （细胞结构蛋白异

常） Waller degeneration （ Waller 变性）

中央型尼氏体溶解正常神经细胞


1. Chromatolysis （尼氏体溶解）


2.Red neuron （红色神经元） ---Coagulation necrosis


1. Chromatolysis （尼氏体溶解） 2. Red neuron （红色神经元） 3. Simple neuronal atrophy （单纯性神经元萎缩） Common in some chronic degenerative diseases


4. Cellular inclusion （包含体形成）

Negri body-rabies （狂犬病）


5. Cell Structure protein change （细胞结构蛋白异常）

Neurofibrillary Tangles-AZ Lewy bodies-PD


6. Waller degeneration （ Waller 变性） Degeneration Demyelination （脱髓鞘） Regeneration

Trichrome 染色：髓鞘染成红色，胶原纤维染成青色，可见髓鞘缺失、崩解。

2. Basic pathology changes of the astrocytes 1. Swelling （肿胀） 2. Reactive astrogliosis （反应性胶质化）

2. Basic pathology changes of the astrocytes

2. Reactive astrogliosis

2. Basic pathology changes of the astrocytes 1. Swelling （肿胀） 2. Reactive astrogliosis （反应性胶质化） 3. Amyloid body （淀粉样小体 )

3. Basic pathology changes of the oligodendrocyte Satellitosis （卫星现象）

4. Basic pathology changes of the ependymal cell Ependymal granulation （颗粒状室管膜

炎）颗粒状室管膜炎正常室管膜细胞

5. Basic pathology changes of the microglia

1. Neuronophgia （噬神经细胞现象） 2. Foamy cell(gitter cell) （格子细胞形

成） 3. Microglial nodules （胶质结节）


噬神经细胞现象neuronophagia

格子细胞 gitter cell


microglial nodules( 胶质结节）

II.Common Complications of CNS

1. Brain edema( 脑水肿 ) 2. Hernia( 脑疝 ) 3. Hydrocephalus( 脑积水 )

1. Brain edema Brain edema ( 脑水肿 ) : increased water content

within the brain parenchyma Vasogenic edema: A state of increased extracellular

fluid volume; Brain tumor, abscess, infarct, hemorrhage Cytotoxic edema: The swelling of cellular elements;

Hypoxia, toxication

1. Brain edema

1. Brain edema

脑水肿

2. Herniation Herniation ( 脑疝形成） : Abnormal protrusion of

brain tissue through an opening.

Causes : Raised ICP (Intracranial pressure) Intracranial expanding lesions – tumor, haematoma,

abscess

2. Herniation

Intracranial pressure (ICP) Within the intact skull, there are 3 major components of

intracranial pressure: the brain, the CSF and blood. Any increase in volume of one of these 3 components will

produce an increase in ICP Normal ICP is 0.6-1.8kPa

2. Herniation-Types

Supracallosal hernia （扣带回疝，大脑镰下疝）

Tentorial hernia （小脑天幕疝，海马沟回疝） Foramen magnum hernia( 枕骨大孔疝，小

脑扁桃体疝）

2. Herniation

扣带回疝

海马沟

回疝

小脑扁桃体疝

3. Hydrocephalus Hydrocephalus( 脑积水 ) refers to the

accumulation of excessive CSF within the ventricular system

3. Hydrocephalus-Types 1. noncommunicating hydrocyphalus ( 非交通性脑积水 ) Obstructive hydrocephalus 2. communicating hydrocyphalus( 交通性脑积水 ) Overproduction of CSF Defective absorption of CSF

3. Hydrocephalus-Types

Causes: Increased secration of CSF ：脉络丛肿瘤 Obstraction to the flow of CSF ：肿瘤、

粘连性阻塞 failure of absorption of CSF ：蛛网膜粒的

闭塞

Dilated lateral ventricles seen in a coronal section

3. Hydrocephalus-Types

III. Infectious diseases of CNS

Epidemic meningitis Epidemic Encephalitis B

Routes of infection

Hematogenous spread Direct implantation Trauma, Nasal or

paranasal sinuses inflammation Invasion via the peripheral nerves

Structure of menginges

Meningitis

Acute suppurative meningitis:bacteria Acute lymphocytic meningitis:virus Chronic meningitis:TB

1. Epidemic meningitis1. Epidemic meningitis

Group A meningococcus accounts for an estimated 80–85% of all cases in the meningitis belt, with epidemics occurring at intervals of 7–14 years.

Suppurative immflamation

1. Epidemic meningitis-1. Epidemic meningitis-TransmissionTransmission The bacteria are transmitted from person-

to-person through droplets of respiratory or throat secretions from carriers

The bacteria overwhelm the body's defenses allowing infection to spread through the bloodstream to the brain.

1. Epidemic meningitis-Gross1. Epidemic meningitis-Gross

There are abundant creamy, purulent exudate, most prominently over the superior surface of the cerebrum.

The exudation full in sulci. The gyri are swollen. The vessels are congested.

1. Epidemic meningitis-Gross1. Epidemic meningitis-Gross

1. Epidemic meningitis-Micro1. Epidemic meningitis-Micro

Neutrophilic exudate, dilated vessels, edema in the subarachnoid space

1. Epidemic meningitis-Clinical 1. Epidemic meningitis-Clinical signssigns Signs of infection (fever, malaise,skin rashes….) Sign of high intracranial pressure a. headache b. vomiting Signs of meningeal irritation a. neck stiffness, episthiotonus （角弓反张） b. Kernig positive

1. Epidemic meningitis-Clinical 1. Epidemic meningitis-Clinical signssigns Signs of infection (fever,malaise,skin rashes….) Sign of high intracranial pressure a. headache b. vomiting Signs of meningeal irritation a. neck stiffness, episthiotonus b. Kernig positive CSF changes: a. cloudy purulent b. abundant neutrophils c. high protein level and reduced glucose level

1. Epidemic meningitis-CSF 1. Epidemic meningitis-CSF valuesvalues

Cells Protein Glucose Pressure

Acute bacterial

PMNs

Acute viral

Lymphs Normal

Chronic(TB)

Lymphs

neutrophil Bacteria

monocyte

1. Epidemic meningitis-CSF 1. Epidemic meningitis-CSF valuesvalues

1. Epidemic Complications1. Epidemic Complications

Hydrocephalus （脑积水） Cranial nerve paralysis （颅神经麻痹） Cerebral ischemia and infarct （脑缺血和梗

死）

Fulminant meningococcal septicemiaFulminant meningococcal septicemia暴发性脑膜炎球菌败血症暴发性脑膜炎球菌败血症

an extreme form of endotoxin-induced sepsis and coagulopathy. The condition is diagnosed clinically by the appearance of hemorrhagic skin lesions and compromised circulation

Fulminant meningococcal Fulminant meningococcal septicemiasepticemia暴发性脑膜炎球菌败血症暴发性脑膜炎球菌败血症

2. Epidemic Encephalitis B2. Epidemic Encephalitis B

Epidemic encephalitis B is acute infectious disease caused by encephalitis B virus

Usually occurs in summer & fall The virus is transmitted by mosquito

Virus

Replication in Mononuclear-phagocyte System (MPS)

CNS

Blood Stream

Blood Brain BarrierBrief Viremia

2. Epidemic Encephalitis B-2. Epidemic Encephalitis B-TransmissionTransmission

Blood Brain Barrier-Blood Brain Barrier- 血脑屏障血脑屏障

2. Epidemic Encephalitis B-Gross2. Epidemic Encephalitis B-Gross

Pathologic location: cerebral parenchyma

2. Epidemic Encephalitis B-Micro2. Epidemic Encephalitis B-Micro

Congestion and inflammation: endothelial cells swelling, perivascular cuffing

Degeneration and necrosis of neurons: softing focus, neruonophagia, satellitosis

Proliferation of microglial cells: microglial nodule


Congestion and inflammation: endothelial cells swelling, perivascular cuffing


Degeneration and necrosis of neurons: softing focus, neruonophagia, satellitosis


Proliferation of microglial cells: microglial nodule

2. Epidemic Encephalitis B-2. Epidemic Encephalitis B- Clinical feature Clinical feature

High fever Headache Vomiting Sleepiness Convulsion 抽搐

V. Tumors of Nerous System

Tumors of CNS Peripheral Nerve Tumors

Tumors of CNS

Comprise: 10% of all tumorsComprise: 10% of all tumors Peak incidence 20-50 yrPeak incidence 20-50 yr Common childhood tumorCommon childhood tumor Supratentorial tumors in adultsSupratentorial tumors in adults Infratentorial tumors in childhoodInfratentorial tumors in childhood Location determines prognosisLocation determines prognosis Rare extra neural metastasisRare extra neural metastasis

WHO Grade Grade I

Slow growing Non-malignant tumors Patients have long-term survival

Grade II Relatively slow growing Sometimes recur as higher grade tumors May be non-malignant or malignant.

Grade III Malignant tumors Often recur as higher grade tumors

Grade IV Highly malignant and aggressive

Tumors of CNS

Gliomas MedulloblastomaMeningiomas

Tumors of CNS

Gliomas---derived from glial cells, include

Astrocytoma

Oligodendrogliomas

Ependymoma

Histologic Classification of Glial Tumors

Astrocytic Tumors Pilocytic (grade 1) Diffuse (grade 2) Anaplastic (grade 3) Glioblastoma (grade 4)Oligodendroglial tumors and mixed variants Oligodendroglioma, well differentiated (grade 2) Anaplastic oligodendroglioma (grade 3) Mixed oligodendroglioma/astrocytoma (grade 2) Mixed anaplastic oligodendroglioma/astrocytoma (grade 3)Ependymal Tumors Myxopapillary ependymoma (grade 1) Ependymoma (grade 2) Anaplastic ependymoma (grade 3)

Astrocytoma

4th to 6th decade, Cerebrum. Grading system based on

Anaplasia Mitotic activity Necrosis Endothelial proliferation

Diffuse (WHO-II), anaplastic (WHO-III) & Glioblastoma (WHO-IV)

Molecular markers: GFAP, Ki67, TP53, EGFR, IDH1, MGMT…

Diffuse Astrocytoma (WHO-II)

Histologic type: fibrillary （纤维型） , protoplasmic（原浆型） , gemistocytic （肥胖细胞型） .

Gross: a poorly defined, gray, infiltrative tumor that expands and distorts the invaded brain. The cut surface of the tumor is either firm, or soft and gelatinous; cystic degeneration may be seen.

Micro: a mild to moderate increase in the number of glial cell nuclei, somewhat variable nuclear pleomorphism, and tumor cells can be seen infiltrating normal tissue.

Glioma Cerebrum

Glioma Cerebrum

A. 低密度细胞，核轻度异型； B. 疏松瘤性间质背景中的肿瘤性纤维星形细胞；C. 弥漫性微囊形成； D. 不同程度的弥漫性 GFAP 表达。

Diffuse Astrocytoma (WHO-II)纤维型星形细胞瘤

A. 弥漫粘液变性； B. 在微囊背景中肿瘤细胞有少许依稀可见的胞浆。

Diffuse Astrocytoma (WHO-II)原浆型星形细胞瘤

A. 肿瘤细胞浆丰富，轻度嗜酸性，核偏向周边并且B. GFAP 强阳性。

Diffuse Astrocytoma (WHO-II)肥胖细胞型星形细胞瘤

A. 高密度细胞； B. 大部分肿瘤细胞核内聚集 TP53 蛋白；C. 部分区域明显的核异型和分裂活性； D. Ki67 阳性率 5-10%

Anaplastic (WHO-III)

Glioblastoma (WHO-IV)

Older adults Median survival: 12 months Highly malignant Diffuse infiltrative tumors

79 岁原发性胶质母细胞瘤患者 MRI 。肿瘤发展迅速，初期为一个小的皮质病灶， 68 天后肿瘤体积明显增大，伴瘤体周围水肿和中央坏死。


A. 具有高度间变的胶质母细胞瘤； B. 腺样 GBM 形成腺样结构； C. GBM 中少突胶质细胞成分。

A. 多个蜿蜒的假栅栏坏死； B. 瘤细胞在坏死周围形成栅栏结构； C. TUNEL 法示细胞凋亡。


Pilocytic Astrocytoma （ WHO-I) Common in childhood Most slow growing of the gliomas Sites: cerebellum, around III IV V., optic nerve Grossly cystic with mural nodule Microscopic

elongated hair-like (pilo) cells Rosenthal fibers

Pilocytic Astrocytoma （ WHO-I)

毛细胞型星形细胞瘤年龄分布

A. 毛细胞型星形细胞瘤生长侵及基底池；B. 大的、多囊性小脑毛细胞型星形细胞瘤突入第四脑室，压迫脑干。

C ， D 典型的双相成分，富有纤维， GFAP 阳性区和少细胞区伴小囊形成， GFAP 阴性

A. 术中印片示长的双极瘤细胞

B. Rosenthal 纤维

Pilocytic Astrocytoma （ WHO-I)

Oligodendroglioma

Cells of origin: Oligodendrocytes Common in cerebral hemispheres Calcifications common Grades:

Low grade (WHO-II) Anaplastic (WHO-III)

Oligodendroglioma(WHOII)

A. 典型的致密分枝状血管网； B. 瘤细胞胞浆透明，细胞膜明显

Tumors of CNS

Gliomas Medulloblastoma

Medulloblastoma （髓母细胞瘤）

Origin: primitive neuroectodermal cells Age: 1st － 2nd decade of life. Most

common brain tumor at this age.

Medulloblastoma( 髓母细胞瘤）


common brain tumor at this age. Site: vermis of cerebellum, may project

into the V ventricule

Cerebellum Medulloblastoma

Medulloblastoma( 髓母细胞瘤）


common brain tumor at this age. Site: vermis of cerebellum, may project

into the V ventricule Subarachnoid dissemination May cause hydrocephalus

A. 肿瘤转移至硬脑膜内表面； B. 肿瘤转移至马尾。

Medulloblastoma-Subarachnoid dissemination

A. 典型的未分化肿瘤细胞片状排列； B. Homer-Wright 菊形团； C. 肿瘤细胞平行排列； D. 产生假腺样结构的栅栏状肿瘤细胞。

Medulloblastoma-Histology

Medulloblastoma-Histology

Homer Wright Rosettes

Tumors of CNS

Gliomas Medulloblastoma Meningiomas

Meningioma

Meningiomas are predominantly benign tumors of adults

Usually attached to the dura, that arise from the meningothelial cell of the arachnoid

More common in women

Meningioma

Gross ： Meningiomas are usually rounded masses with a well-defined dural base that compress underlying brain but are easily separated from it.

Meningioma-grossA.矢状窦旁脑膜瘤压迫周围顶叶脑组织

B.蝶骨中翼脑膜瘤包绕颈动脉

C.前颅凹冠状切面显示位于嗅沟的脑膜瘤

D.蝶骨翼的脑膜瘤

E.斜坡脑膜瘤压迫脑干

F.脊髓脑膜瘤压迫脊髓

Meningioma-histologyA.上皮型脑膜瘤伴核内包涵体

B.纤维型脑膜瘤平行束状排列

C.过渡型脑膜瘤同心圆洋葱球样结构

D.砂粒体型脑膜瘤有大量钙化的砂粒体

E.脊索瘤样脑膜瘤，丰富粘液背景里可见嗜伊红肿瘤细胞

F.血管型脑膜瘤，大量血管之间为脑膜瘤细胞。

V. Tumors of Nerous System

Tumors of CNS Peripheral Nerve Tumors

Peripheral Nerve Tumors Nerve Sheath Tumors Neurilemmoma （神经鞘瘤） Neurofibroma （神经纤维瘤） Perineurioma （神经束膜瘤） Malignant Peripheral Nrve Sheath Tumor （恶性外周神经鞘瘤） Neural cell tumor Neuroblastoma （神经母细胞瘤） Ganglioneuroma （节细胞神经瘤）

Neurilemmoma 神经鞘瘤 (Schwannoma)

Common SiteA. 左侧小脑桥脑角听神经瘤B. 脊髓神经鞘瘤

Neurilemmoma 神经鞘瘤

Gross


Histology: Antoni A & B

A. 双相性：多细胞 Antoni A 区和低密度细胞区 Antoni B 区；B. 神经鞘瘤细胞核形成栅栏状结构

Antony A Antony B


Neurofibroma 神经纤维瘤

Schwann cell, perineurial cells & fibroblasts Two types:

Classic form - Cutaneous / nerve - Solitary collagen matrix, spindle cells

Plexiform ( 丛状的 )- Multiple, infiltrative, myxoid

脊髓神经纤维瘤，切面质硬均匀

Neurofibroma-gross

A. 皮肤神经纤维瘤弥漫浸润真皮

B. 丛状神经纤维瘤

C. 肿瘤细胞核小，卵圆。肿瘤细胞产生嗜伊红条带状胶原纤维

D. 粗胶原形成 “胡萝卜碎片” 外观

Neurofibroma-histology

Neurofibromatosis( 神经纤维瘤病 )

Type I (common):(17q)

Plexiform & solitary neurofibromas Optic nerve gliomas, Lisch nodules （虹膜色素缺

陷瘤） , Café au lait spots （咖啡牛奶斑） .


Type I (common):(17q)

Plexiform & solitary neurofibromas Optic nerve gliomas, Lisch nodules （虹膜色素缺

陷瘤） , Café au lait spots （咖啡牛奶斑） . Type II (rare):(22q)

Bilateral acoustic schwannoma/osis Multiple meningioma/osis, ependymoma of

spinal cord

Multiple neurofibromasCafé-au-lait spots


Case Study

22-year-old female, presented with a history of headache and convulsion of four months duration.

Brain MRI : Right frontal lobe lesion with an irregular outline, mass-effect, peripheral contrast uptake, and central necrosis.

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Diseases of the Nervous System