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The Nervous System

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(1)

The Nervous System

Nam Deuk Kim

Pusan National University

1

(2)

Contents

I. The CNS

1. Anatomy & histology

2. Congenital malformations of the CNS

3. CNS trauma

4. Circulatory disorders of the 5. Hydrocephalus & CNS

cerebrospinal fluid (CSF)

6. Infectious diseases of the CNS 7. Viral encephalomyelitides

8. Prion disease

9. Demyelinating diseases of the 10. Storage diseases expressed CNS

in neurons

11. Metabolic neuronal disorders 12. Metabolic disorders

13. Neurodegenerative diseases

II. The PNS

1. Reactions to injury 2. Axonal degeneration 3. Peripheral neuropathies 4. Tumors of the PNS

(3)

I. Nervous System

The CNS (central nervous system)

Brain

Spinal cord

Surrounded by membranes called meninges

• Neurons (nerve cells) and neuroglia (supporting cells)

• A sensory nerve or afferent:

transmits impulses into the nervous system

• A motor or efferent nerve:

transmits impulses from brain or spinal cord to muscle

• The transmission of a nerve impulse is by means of

neurotransmitters

• Some important ones:

acetylcholine, norepinephrine, dopamine

• Neuronal injuries:

a. Chromatolysis (염색질 융해) b. Atrophy (위축)

c. Neuronophagia (신경세포 식작용) d. Intraneuronal inclusions (신경세

포내 봉입체)

Neurons

Pigmented neurons

3

(4)

Nervous System Organization

(5)

Meninges

1. Dura: firm, outer 2. Arachnoid: middle

• (Subarachnoid space: space between arachnoid and pia) contains

– CSF (cerebrospinal fluid) – Strands of arachnoid

connective

tissue 3. Pia: thin, inner

– Adheres to

brain and spinal cord

Cerebrospinal Fluid (CSF)

5

(6)

Brain

1. Cerebrum; 2. Brain stem; 3. Cerebellum

Brain is hollow with four cavities called ventricles

• Tissue of brain and spinal cord

– Nerve cells = neurons

– Supporting cells = neuroglia

• Arterial blood supply

– Large vessels enter base of skull

– Vessels join to form arterial circle at base of brain

• Venous blood

– Returned from brain into large venous sinuses in dura

– Sinuses eventually drain into jugular veins

(7)

Neuroglia

7

(8)

• Astrocytes function in the response of the CNS to injury: gemistocytic astrocytes, corpora amylacea, astrocytomas

• Ependymal cells regulate

cerebrospinal fluid (CSF) transfer:

ependymomas

• Microglia are the phagocytic cells of

(9)

9

(10)
(11)

2. Congenital malformations of the CNS

(선천기형)

11

(12)

 Spina bifida (척추갈림증)

A. Occult spina bifida (잠재척추갈림증) B. Meningocele (수막탈출증)

C. Meningomyelocele (수막척수탈출증) D. Failure of the neural tube to form

and separate from the surface ectoderm

• Anencephaly (무뇌증) and spina

bifida (척추갈림증): 2/1,000 births in the US

• Deficiency of folic acid: causing neural tube defects

• Intake of 0.4 mg of folic acid daily

 Dysraphic defects (유합결손)

 Epilepsy (간질): seizure (발작)

(13)

Neural Tube Defects

• Anencephaly (무뇌증)

13

(14)

Neural Tube Defects

Large thoracic

meningomyelocele (수막척추 탈출증) covered only by a thin membrane.

Very large meningomyelocele that was associated with

severe neurologic deficit.

(15)

3. CNS Trauma

• Results in:

a. Intracranial hemorrhages

b. Direct damage (penetrating trauma) c. Paralysis (spinal cord injuries)

• Table 28-2:

1) Cerebral contusion results from brain trauma

• Pathogenesis:

- Contusion (뇌 타박상) - Coup (타격손상)

- Contrecoup (반대측 타격손상)

- Concussion (뇌진탕): a transient loss of consciousness due to trauma that causes a rapid torque on the

brainstem, leading to a paralysis of neurons of the reticular formation

A, Multiple contusions involving the inferior surfaces of frontal lobes, anterior temporal lobes, and cerebellum. B, Acute contusions are present in both temporal lobes, with areas of hemorrhage and tissue disruption. C, Remote contusions are

present on the inferior frontal surface of this brain, with a yellow color (associated with the term plaque jaune).

15

(16)

Biomechanics of cerebral contusion. The cerebral hemispheres float in the cerebrospinal fluid. Rapid deceleration or

acceleration of the skull causes the cortex to impact forcefully into the anterior and middle fossae.

The position of a contusion is determined by the

direction of the force and the intracranial anatomy.

Remote contusions of the brain. Bilateral large frontal and smaller temporal tip contusions were cleared out by

macrophages, leaving residual

hemosiderin-stained divots. Also, note the involvement of the olfactory bulbs—

anosmia (loss of sense of smell) is the

most common cranial neuropathy following traumatic brain injury.

(17)

대뇌좌상(Cerebral Contusion)

A, Multiple contusions involving the inferior surfaces of frontal lobes, anterior temporal lobes, and cerebellum. B, Acute contusions are present in both temporal lobes, with areas of hemorrhage and tissue disruption. C, Remote contusions are present on the inferior frontal surface of this brain, with a yellow color (associated with the term plaque jaune).

17

(18)

Cerebral Injury

(19)

2) Epidural hematoma (경질막 바깥혈종 ) results from bleeding between the skull & dura

Development of an epidural hematoma.

Laceration of a branch of the middle

meningeal artery by the sharp bony edges of a skull fracture initiates bleeding under arterial pressure that dissects the dura from the calvaria and produces an

expanding hematoma. After an

asymptomatic interval of several hours, subfalcine and transtentorial herniation occur, and if the hematoma is not

evacuated, lethal Duret hemorrhages will occur.

Epidural hematoma covering a portion of the dura. Multiple small contusions are seen in the temporal lobe.

Epidural

hematoma. A discoid mass of fresh hemorrhage overlies the dura covering

frontal:parietal cortex but does not transgress the coronal sutures. 19

(20)

3) Subdural Hematoma (경질막밑혈종)

A, Large organizing subdural hematoma attached to the dura. B, Coronal section of the brain showing compression of the

hemisphere underlying the hematoma.

Development of a subdural hematoma. A.

With head trauma, the dura moves with the skull, and the arachnoid moves with the cerebrum. As a result, the bridging veins are sheared as they cross between the dura and the arachnoid. Venous bleeding creates a hematoma in the expansile

subdural space. Subsequent transtentorial herniation is life-threatening. B. The right hemisphere exhibits a large collection of blood in the “subdural space”, owing to rupture of the bridging veins.

(21)

4) Subarachnoid Hemorrhage (거미막밑 출혈) often occurs in the circle of Willis

• 어떠한 원인이건 지주막하부 공 간 내로 출혈이 있는 것

• 2/3의 경우 그 전에 존재하던 동 맥류가 파열된 것

• 10%의 경우 동정맥 기형으로 유래

CT scan of the brain showing subarachnoid hemorrhage as a white area in the center and

stretching into the sulci to either side (marked by the arrow)

5) Spinal cord injuries often result from trauma

Spinal injury. A. Numerous different angles of force can be applied to the highly vulnerable cervical spine. Posterior (hyperextension) and anterior (hyperflexion) injuries are the most

common. Hyperextension injury causes rupture of the anterior spinal ligament and excessive

posterior angulation. Hyperflexion injury causes compression associated with a “teardrop” fracture of a vertebral body and produces excessive

forward angulation of the cord.. 21

(22)

4. Circulatory Disorders (혈관질환) 1) Vascular malformations (혈관기

형) are congenital lesions present in the CNS

• Arteriovenous malformation (동정 맥 기형): 가장 흔한 선천성 혈관 기형

• Cavernous angioma (해면혈관종):

선천성 비정상; 동정맥 기형보다 흔하지 않음

• Telangiectasia (모세혈관 확장증):

• Venous angioma (정맥혈관종):

2) Cerebral aneurysms result from congenital lesions & intravascular pressure (동맥류)

• Berry aneurysm (딸기 동맥류):

Rupture causes subarachnoid hemorrhage

• Atherosclerotic aneurysm (죽상경 화성 동맥류): most commonly result in thrombosis rather than rupture

• Mycotic aneurysm (진균성 동맥 류): result from septic emboli that originate in infected cardiac

valves & can cause arterial rupture, cerebral abscess, or meningitis.

(23)

Berry Aneurysm(딸기 동맥류)

Common sites of saccular (berry) aneurysms in the circle of Willis.

전대뇌동맥

전교통동맥

내경동맥

후대뇌동맥

후교통동맥

중대뇌동맥

23

(24)

Cerebral Aneurysm

• Cerebral angiogram

• Treatment: occluding (closing off) the

aneurysm by applying a small metal clip to the narrow neck of the sac at its attachment to the arterial wall

A large arteriosclerotic aneurysm (arrows)

that compressed

and distorted the

(25)

3) Cerebral hemorrhage (뇌출혈) is most often associated with

hypertension

• Charchot-Bouchard aneurysm (샤 르코-부샤르 동맥류)

:  rupture at:

a. Basal ganglia-thalamus (65%) b. Pons (15%)

c. Cerebellum (8%)

• Rupture of Charchot-Bouchard aneurysm  leads to:

a. Cerebral hemorrhage (hemorrhagic stroke) 

intraventricular hemorrhage b. Pontine hemorrhage

c. Cerebellar hemorrhage

A, Massive hypertensive hemorrhage rupturing into a lateral ventricle. B,

Hypertensive hemorrhage in the pons, with extension to fill the fourth ventricle.

25

(26)

Stroke (뇌졸중)

• 뇌졸중이라는 말은, 원래 졸중(卒中)이 ‘갑작스레 당한다, 갑자 기 탈이 난다’는 뜻.

• '어떠한 원인으로 인해서 갑자기 뇌혈관이 터지거나 막혀서 뇌 쪽으로 가는 혈액순환이 되지 않거나 직접적인 뇌손상으로 인 해 뇌기능에 이상을 일으켜, 의식장해, 편마비(한쪽 팔다리 마 비), 어지럼증, 두통 등이 돌발적으로 발생한 상태'를 말함.

• 뇌혈관질환 (cerebrovascular disease)이나

• 뇌혈관발작 [cerebrovascular accident (CVA), brain stroke],

• 또는 일반적으로 뇌졸중이라는 말을 주로 사용함.

(27)

4) Stroke is most often associated with cerebral ischemia (허혈) &

infarction (경색)

• 대뇌: 많은 혈액과 산소 필요 a. 체중의 1~2%

b. 심박출량의 15%

c. 인체 산소 소모량의 20% 필요 A. Global ischemia (전 허혈):

a. by hypoxia (near-drowning, carbon-monoxide poisoning, suffocation) or generalized decreased blood flow (cardiac arrest, external hemorrhage) b. Watershed infarcts (분수계성 경 c. Laminar necrosis (층괴사) 색)

B. Regional ischemia (국소 허혈):

results from occlusive cerebrovascular disease (cerebral artery thrombosis)

Mechanisms of injury in global ischemia. A global insult induces lesions that reflect the vascular architecture (watershed infarcts, laminar necrosis) and the selective

vulnerability of individual neuronal systems (pyramidal cells of the Sommer sector,

Purkinje cells, laminar necrosis). Both rheologic (blood flow) and neurochemical (excitotoxicity) factors may be operational in laminar necrosis.

27

(28)

B. Regional ischemia (국소 허혈 및 대뇌 경색)

a. Transient Ischemic Attack (TIA)

• Brief episodes of neurologic dysfunction such as temporary paralysis of an arm or leg, loss of speech, or disturbances of vision.

• Dysfunction result of embolization of material from plaque in the

carotid artery

• One-third of patients eventually suffer major stroke

• Treatments:

- either of surgical resection of the ulcerated plaque in the carotid artery by means of a carotid endarterectomy

- or administration of drugs that decrease the likelihood that thrombi will form on the

ulcerated plaques, thereby

reducing the risk of embolization

• Pathology & Clinical features:

a. Large extracranial & intracranial vessel occlusion (carotid,

vertebral, & basilar arteries)

b. Circle of Willis vessel occlusion c. Parenchymal artery & arteriolar

occlusion

d. Capillary bed occlusion:

Caisson disease

e. Cerebral vein occlusion

A. Distribution of cerebral infarcts.

Acute cerebral infarct

histopathology.

An 18-hour-old cerebral infarct (left) shows edema,

hypereosinophilic neurons and

perivascular polymorphonucle ar leukocytes.

(29)

• Cerebral infarct by either a thrombus or an embolus

Cerebral Thrombi and Emboli

29

(30)

• Encephalomalacia (뇌연화증, brain softening)

• In most cerebral infarcts, no blood leaks into brain; called an ischemic infarct

• However, in some cases, a small amount of blood leaks into

the damaged brain tissue; called a hemorrhagic infarct

(31)

Arteriosclerosis of extracranial arteries

• A stroke may also be caused by sclerosis of a major artery arising from aorta to supply the brain, before the vessel enters the brain; a commonly affected site is the carotid artery in neck, where arteriosclerotic plaque may narrow the

lumen and reduce cerebral blood flow

31

(32)
(33)

Manifestations of Stroke:

• Depend on the location and the amount of brain tissue injured.

1. Little functional disturbance 2. Partial paralysis

3. Various sensory disturbances 4. Hemiplegia or hemiparesis

33

(34)

Therapeutic management

1) 고혈압 조절에 사용되는 혈압강하제

• 이뇨제약물

• 뇌혈관확장작용제 : hydralazine, nitroprusside

• 싞경젃 및 교감싞경차단제: trimetaphan, guanethidine 등

2) 뇌부종 조절에 사용되는 약제

• 부싞피질호르몬제(dexamethasone),

Mannitol, Glycerol, Dextran, 이뇨제(라식스) 3) 뇌혈관 확장제

• 이산화탄소 (CO2)가 제일 강력,

• 약물: papaverine, hexobendine, diamox, betahistine, isoxuprine, cyclandelate 등 4) 항응고제 (anticoagulation therapy)

• Heparin, warfarin, low molecular weight heparin (LMWH), Coumarin 등

5) 혈전용해제 (thrombolytic therapy)

• streptokinase, urokinase, tissue plasminogen activator(tPA) 등

6) 항혈소판제제 (antiplatelet therapy)

• 동맥혈관내 혈젂 형성을 차단; aspirin, triclopidine

7) 지질 강하제

• 뇌졸중홖자에서 혈중지질이 높은데 이 경우 clofibrate, nicotinic acid, liparoid 등 사용.

(35)

Rehabilitation of the Stroke Patient

• To regain the ability to walk

• To learn self-care activities, such as washing, combing the hair, and eating, that may have been impaired by the stroke

• To prevent stiffness and limitation of motion in the joints of the paralyzed limbs

• To make an emotional adjustment to the disability

35

(36)

증상이 없다가 어느 날 갑자기 찾아오는 뇌졸중, 미리 진단해 보기(조선일보 2013.4.21)

(37)

5. Hydrocephalus (물뇌증) &

cerebrospinal fluid (뇌척수액, CSF)

• 수두증: 선천성이거나 후천성 이며, CSF가 과량이고 그 결과 로 뇌실계가 확장된 것

a. Noncommunicating

hydrocephalus (무교통 물뇌 증): 뇌실방 내에서 발생 b. Communicating

hydrocephalus (교통 물뇌증):

뇌실계 내에 폐색이 없고, 지주 막 융모에 의한 CSF의 재흡수 가 손상된 것

• Congenital

– Obstruction of aqueduct

– Absence of openings in roof of fourth ventricle

• Acquired

– Obstruction in region of fourth ventricle

A, Hydrocephalus.

Dilated lateral

ventricles seen in a coronal section through the midthalamus.

B, Midsagittal plane T1-weighted

magnetic resonance image of a child with communicating hydrocephalus, involving all

ventricles.

37

(38)

6. Infectious diseases of the CNS System

• Infection by: Bacteria, Viruses, Parasites, & Prion

• Infections affecting

meninges

=

meningitis (수막염)

- Infections of

brain tissue = encephalitis (뇌염)

- If both involved, meningoencephalitis (수막뇌염)

-

An infection of the spinal cord = myelitis (척수염)

1) Meningitis (수막염) is most frequently bacterial or viral in origin

(39)

A. Bacterial meningitis (세균수막염)

The most common bacteria:

- E. coli

- Hemophilus influenzae

- Streptococcus pneumoniae

)

- Neisseria meningitidis

• Clinical features:

- Headache, vomiting, & fever - Children: may also have

convulsions

- Classic findings: cervical rigidity, inability to straighten the knee following hip flexion, owing to pain (Kernig sign), & knee & hip flexion following neck flexion secondary to pain (Brudzinski sign)

- Lumbar puncture:

polymorphonuclear leukocytes, increased protein, & decreased glucose level of the CSF

39

One of the physically demonstrable symptoms of meningitis is Kernig's sign. Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees.

One of the physically demonstrable symptoms of meningitis is

Brudzinski's sign. Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed.

(40)

B. Tuberculous meningitis(결핵수막염)

• caused by Mycobacterium

tuberculosis, is more common in people from countries where

tuberculosis is endemic, but is also encountered in persons with immune problems, such as AIDS C. Syphilitic meningitis(매독수막염)

Treponema pallidum

• Three severe manifestations of tertiary syphilis

a. Meningovascular syphilis b. Tabes dorsalis

c. Dementia paralytica (luetic dementia)

D. Viral meningitis(바이러스 수막염)

• Enterovirus (coxsackie B virus, echovirus)

• Arboviruses: important group responsible for many cases of meningitis and encephalitis

• Viruses infect birds and animals as well as humans and are

• Types of encephalitis

a. Western equine encephalitis b. Eastern equine encephalitis c. St. Louis encephalitis

d. California encephalitis

e. West Nile virus: a “foreign” virus from Africa, first case identified in 1999 in New York City area

2) Cryptococcal meningitis(크립토 콕쿠스 수막염) occurs most

frequently in immunocompromised persons

Cryptococcus neoformans

• Occurs most frequently in

immunocompromised persons

• In Africa, cryptococcal meningitis is estimated to be the most

common cause of meningitis and it accounts for 20–25% of AIDS- related deaths in Africa.

(41)

3) Amebic meningoencephalitis (아 메바수막뇌염) may be water-

borne

• A disease of the central nervous system caused by infection from

Naegleria fowleri and

Acanthamoeba.

Naegleria fowleri

propagates in warm, stagnant bodies of

freshwater (typically during the summer months), and enters the central nervous system after

insufflation of infected water by attaching itself to the olfactory nerve

• It then migrates through the cribiform plate and into the

olfactory bulbs of the forebrain, where it multiplies itself greatly by feeding on nerve tissue.

• During this stage, occurring approximately 3–7 days post- infection, the typical symptoms are parosmia, rapidly progressing to anosmia (with resultant

ageusia) as the nerve cells of the olfactory bulbs are consumed and replaced with necrotic lesions.

Histopathology of amebic

meningoencephalitis due to Naegleria fowleri. Direct fluorescent antibody stain.

41

(42)

4) Cerebral abscess (뇌 고름집) is the result of cerebritis

• Bloodborne microorganisms  cerebritis (뇌염)

Brain abscess development and its complications. A cerebral abscess may cause death through the production of secondary abscesses with intraventricular rupture; alternatively, death may result from transtentorial herniation. The abscess

consists of a necrotic purulent core, a layer Cerebral abscess. A young man with

bacterial endocarditis developed an abscess in the left basal ganglia.

(43)

7. 바이러스성 뇌척수염 (Viral Encephalomyelitis)

• CNS의 실질에 바이러스 감염

1) West Nile virus(서부 나일강 열바이러스) is a recently emergent pathogen 2) Poliomyelitis (폴리오, 회색질척수염) refers to CNS infection by a

single-stranded RNA virus

3) Rabies (광견병) is a fatal infection transmitted by animal saliva 4) Herpes simplex virus (단순헤르페스바이러스 및 관련 감염) is the

most common cause of nonepidemic encephalitis

5) Arbovirus encephalitis (아르보바이러스 뇌염) are transmistted to humans by infected mosquitos or tick bites

6) Subacute Sclerosing Panencephalitis (SSPE, 아급성 경화 범뇌염) is caused by the measles virus

7) Progressive multifocal leukoencephalopathy (진행성 다초점 백색질뇌 증) most often affects immnocompromised patients

8) AIDS encephalopathy(후천성면역결핍증 뇌병증) is often a primary manifestation of HIV infection of the CNS

43

(44)
(45)

1)West Nile virus is a recently emergent pathogen

• A mosquito-borne zoonotic

arbovirus belonging to the genus

• This flavivirus is found in

temperate and tropical regions of the world.

• It was first identified in the West Nile subregion in the East African nation of Uganda in 1937.

• The incubation period for WNV – the amount of time from infection to symptom onset – is typically from between 2–15 days.

• Headache can be a prominent symptom of WNV fever,

meningitis, encephalitis,

menigoencephalitis and it may or may not be present in

poliomyelytis-like syndrome thus headache is not a useful indicator of neuroinvasive disease.

• West Nile Fever (WNF), which occurs in 20% of cases, is a febrile syndrome which causes flu-like symptoms.

• West Nile Neuroinvasive Disease

(WNND), which occurs in less than 1%

of cases, is when the virus infects the CNS resulting in meningitis,

encephalitis, meningoencephalitis or a poliomyelitis-like syndrome.

• West Nile virus encephalitis (WNE) is the most common neuroinvasive

manifestation of WNND. WNE presents with similar symptoms to other viral encephalitis with fever,

headaches, and altered mental status.

• West Nile meningitis (WNM) usually involves fever, headache, and stiff neck.

• West Nile meningoencephalitis is inflammation of both the brain (encephalitis) and meninges (meningitis).

• West Nile poliomyelitis (WNP), an acute flaccid paralysis syndrome

associated with WNV infection, is less common than WNM or WNE.

45

(46)

2) Poliomyelitis (폴리오, 회색질척수염) refers to CNS infection by a single- stranded RNA virus

• an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route.

• Inflammation of the spinal cord’s grey matter  fever, headache, & malaise

 meningitis & variable paralysis

• Death can result from respiratory failure following paralysis of the respiratory muscles.

3) Rabies (광견병) is a fatal

infection transmitted by animal saliva

• a viral disease that causes acute encephalitis in warm-blooded

animals.

• The disease is zoonotic, meaning it can be transmitted from one

species to another, such as from dogs to humans, commonly by a bite from an infected animal.

A man with an atrophied right leg due to

poliomyelitis

Dog with rabies virus

(47)

4) Herpes simplex virus (단순헤르페스바이러스) is the most common cause of nonepidemic encephalitis (비유행성 뇌염)

• Herpes simplex virus type 1 (HSV-1)  results in swollen, hemorrhagic, necrotic brain parenchyma, with perivascular lymphocytic cuffing

• Herpes simplex virus type 2 (HSV-2) (genital herpes)  newborns during passage through the birth canal  severe neonatal

encephalitis

Herpes simplex encephalitis. The infected

neurons display intranuclear, eosinophilic viral inclusions (Cowdry A inclusions) that fill the nuclei (arrows). The presence of these findings is extremely valuable in guiding diagnostic

evaluation as a limited number of viruses produce Cowdry A inclusions.

Herpes simplex encephalitis. Microscopically, the specimen exhibits pronounced

perivascular lymphocytic inflammation. This finding indicates that active inflammation is present, but is not etiologically specific.

47

(48)

6) Subacute sclerosing

panencephalitis (SSPE, 아급성 경 화 범뇌염) is caused by the

measles virus

• 홍역바이러스에 의해 야기되는 드문 뇌의 바이러스 감염

• 특징:

a. 유아기에 발생하는 잠행성 뇌염 b. 장기간의 경과

c. 염증, 특히 대뇌 회백질의 염증 등 5) Arbovirus encephalitis (아르보바

이러스 뇌염) are transmistted to humans by infected mosquitos or tick bites

• St. Louis encephalitis

• Western equine encephalitis

• Tickborne encephalitis

• From flulike symptoms to

meningoencephalitis associated with severe inflammation of the gray matter, necrosis, & vessel thrombosis

• Chronic long-term sequelae:

mental retardation, neurologic deficits, particularly in young children.

(49)

7) Progressive multifocal

leukoencephalopathy (PML, 진행다

초점백색질뇌증) most often affects immunocompromised patients

• A rare and usually fatal viral disease characterized by progressive damage or

inflammation of the white matter of the brain at multiple locations.

• Caused by viruses, the JC virus &

SV40 which is normally present and kept under control by the immune system.

• It occurs almost exclusively in people with severe immune deficiency, such as transplant patients on immunosuppressive medications, receiving certain kinds of chemotherapy, receiving natalizumab for multiple sclerosis, on long-term efalizumab (Raptiva) for psoriasis, or have AIDS.

• Death often occurs within 6 months.

8) AIDS encephalopathy is often a primary manifestation of HIV

infection of the CNS

• Occurs as a direct effect of

macrophage & microglial infection by the HIV-1 retrovirus

• A Primary encephalopathy

• A leukoencephalopathy

• A lymphocytic meningitis

 AIDS dementia complex

Human

immunodeficiency virus (HIV)

encephalitis or encephalopathy (HIVE).

Multinucleated

giant cells (arrows) often in a

perivascular location are characteristic of HIV encephalitis.

Inset. 49

(50)

진행성 다초점 백색질뇌증

(Progressive Multifocal Leukoencephalopathy, PML)

(51)

8. Prion Diseases • Two types:

a. Sporadic forms: major b. Familial forms: minor

• Prion protein (PrP): 30-kDa;

infectious and transmissible

• “Spongiform change” caused by intracellular vacuoles in neurons and glia

• Most of these patients develop progressive dementia

• The most common clinical presentation: CJD

• 1982: Stanley F. Prusiner

• 1997: Nobel prize in Physiology and Medicine

1997년 노벨

생리의학상 수상자

미국 Stanly B. Prusiner 박사

51

(52)

도식화된 이 그림은 어떻게 prion으로 유발되는 다양한 질병들이 뇌의 다른 부분 들에 영향을 미치는지 보여준다. BSE의 경우 brain stem이 영향을 받고, FFI의 경

(53)

Molecular pathogenesis of prion disorders.

Creutzfeldt-Jakob disease.

The unique mode of

“reproduction” of the prion is the autocatalytic conversion of native α-helix:rich cellular prion protein into a β-

sheet:rich pathogenic form that has a strong tendency toward aggregation.

53

(54)

Creutzfeldt-Jacob Disease (CJD)

• Rapidly progressive dementia

1. Sporadic (about 85%) form (sCJD) occurs with an annual incidence of approximately 1 case per 1 million

population and account for about 85%

of cases of CJD

• ~200 cases/year/USA

2. Familial (fCJD) and transmitted forms (vCJD): about 15%

• Peak incidence in the seventh decade

3. Iatrogenic transmission (iCJD): by a. corneal transplantation

b. deep implantation electrodes c. contaminated preparations of

human growth hormone

d. contaminated human tissues [eg, 라이요두라(Lyodura)]

4. New variant CJD (vCJD)

• Clinical features:

a. initial subtle changes in memory and behavior

b. followed by a rapidly

progressive dementia, often with pronounced involuntary jerking muscle contractions on sudden stimulation (startle myoclonus) c. Signs of cerebellar dysfunctions,

usually manifested as ataxia, are present in a minority of patients

• Extensive atrophy of involved gray matter

• Uniformly fatal

• Average duration of only 7 months

(55)

의인성 CJD

• 1980년대 중반 뇌수술을 받은 홖자가 당시 다른 사람의 인체 조직을 수술 자리에 이식 받았다가 '인갂 광우병'처럼 뇌기능이 급속히 망가지는 크로이츠펠트야코브병(CJD)인 이 른바 '의인성(醫因性·iatrogenic) CJD'에 걸려 사망핚 사례가 국내 처음으로 확인

• 54세 여성인 A씨는 지난 1987년 뇌 핚 곳에 물이 차오르는 뇌수막종을 앓아 종양과 이를 둘러싼 뇌경막을 함께 제거하는 수술을 받았 음.

• 당시 수술 부위를 덮기 위해 1980년대 제조 돼 쓰이던 독일제 수입 뇌경막 제품(라이요 두라, Lyodura)을 뇌 표면에 이식받음.

• 이후 별다른 증세 없이 지내던 A씨에게 23년 맊인 작년부터 얼굴과 발 감각장애와 운동장 애·경렦 등 뇌질홖 증세가 생겼음.

• 그러다 증세가 급속히 악화해 증상 발생 5개 월 맊인 2010년 11월 사망했음.

• CJD는 잠복기가 20~30년임

광우병처럼 뇌에 스펀지 같은 구멍이 뚫려 뇌기능을 잃 게 되는 치명적 젂염병인 '크로이츠펠트야콥병(CJD)'에 걸려 숨짂 사례가 국내에서 공식 확인됐다. 사짂은 질병 관리본부와 핚림대 의대 김윤중 교수팀이 발표핚 논문에 포함된 CJD 사망자의 뇌속 변화 영상. 맦 왼쪽은 홖자의 싞경학적인 증상이 있은 지 약 6주 후에 촬영된 것으로, 대상회(띠이랑)와 미상핵에서 싞호 강도 증가가 미세하게 나타나 있다. 하지맊 10주후 영상(중앙)에는 싞경학적 산 호강도가 좀 더 분명해졌으며, 12주후 영상(오른쪽)은 양 쪽 기저핵과 피질에서 광범위핚 높은 싞호 강도가 관찰

됐다. /연합뉴스 55

(56)

국내 의인성 CJD: 2명 발생  2명 사망

• 첫번째 홖자: 1987년(당시 31 세) 뇌수막종 수술후 ‘라이오 듀라(Lyodura)’ 이식 수술

23년맊인 54세에 사망

• 두번째 홖자 백모씨: 1988년 5월(당시 25세) 뇌경막 대용제 품인 ‘라이오듀라(Lyodura)’ 이 식 후 의인성 CJD 증상  2011년 12월 공식 확인  2013년 1월 27일 사망(25년맊 인 50세)

• 25년 정도 경과 뒤 마지막 1 년 동앆 증세가 급속도로 악 화되는 것이 특징

(57)

CJD - spongiform in the cerebral cortex

Kuru-cerebellar cortex - PrP

sc

Neuron with

vacuoles

57

(58)

Variant Creutzfeldt-Jakob Disease

• vCJD (인간 광우병)

• Starting in March 1996 in the U.K.; different from typical CJD

• Young adults (average age 29 years)

• More slow progress (median of 14 months)

• Features:

a. Presence of extensive cortical plaques with a surrounding halo of spongiform change

b. No alterations in the

PRNP

gene; Met/Met homozygotes at codon 129

• Link between vCJD and bovine spongiform encephalopathy (광우

• From October 1996 to November 병) 2002, 129 cases of vCJD have been reported in the United

Kingdom (UK), six in France and

• Insufficient information is

available at present to make any well-founded prediction about the future number of vCJD cases.

• Early in the illness, patients usually experience psychiatric

symptoms, which most commonly take the form of depression or, less often, a schizophrenia-like psychosis.

• Unusual sensory symptoms, such as "stickiness" of the skin, have been experienced by half of the cases early in the illness.

• Neurological signs, including unsteadiness, difficulty walking and involuntary movements,

develop as the illness progresses and, by the time of death,

patients become completely immobile and mute.

(59)

http://www.cdc.gov/ncidod/dvrd/vcjd/factsheet_nvcjd.htm

vCJD in England

59

(60)

vCJD in England

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