1 Chapter 29. Nervous System Central Nervous System Peripheral Nervous System 2 Central Nervous System 3 Neuron and neuroglial cell
Neuron
Neuroglial cell astrocyte
oligodendrocyte ependymal cell microglial cell 4 Neurons
Anatomy
Centrally located round nucleus & prominent nucleolus 핵소체
Cytoplasm: prominent basophilic granules (Nissl bodies 니슬소체) → rough endoplasmic reticulum + ribosomes Myelination 수초화: by oligodendrocyte → rapid transmission
5 Injuries of neurons
Neurons are exquisitely sensitive to injury, with a limited ability to regenerate and very little capacity to recover after demyelination
chromatolysis 염색질융해: a reversible process that involves neuronal swelling, cytoplasmic expansion, eccentric positioning of the nucleus
atrophy
neuronophagia 신경세포포식: phagocytosis of neuronal debris by brain macrophages or microglia 6
7 Neuroglial cells
Astrocytes 별아교세포 → response to injury
"star-shaped", supportive
can be identified by GFAP (glial fibrillary acidic protein) stain
can be identified by GFAP (glial fibrillary acidic protein) stain
Following injury, astrocytes proliferate locally and increase cytoplasmic GFAP synthesis → gemistocytic astrocytes 팽대세포성 별아교세포
gliosis 별아교세포종 ~ a proliferation of astrocytes in damaged areas
→ formation of a glial scar
Oligodendrocyte (oligodendroglia) 희소돌기아교세포 myelin formation: demyelination → disease Ependymal cells 뇌실막세포
regulate the fluid transfer between the CSF and the CNS.
Microglia 미세아교세포
Phagocytic cells of the CNS
after injury, the proliferation of microglia results in diffuse gliosis and in the formation of microglial nodules gitter cells 격자세포: microglias with intracellular accumulation of cellular debirs and lipids
8 Congenital malformations of the CNS
Dysraphic defects 유합결손 (e.g. spina bifida 척추갈림증) Epilepsy 간질 (seizures)
transient disturbances in brain functions.
Microscopically, the brains of patients with epilepsy often demonstrate focal gliosis (glial scarring), although it is unclear whether this represents a cause or effect of the seizure activity.
9 CNS trauma 중추신경계 외상 1) Cerebral contusion 뇌타박상
damage of the cortex
coup injury 타격손상 (site of impact) vs. contrecoup injury 반대측 타격 손상 cf. concussion 뇌진탕
(a transient loss of consciousness) 10 Meninges 뇌척수막?
Dura mater 경질막
Arachnoid mater 뇌거미막, 뇌지주막
Subarachnoid space 거미막밑공간, 지주막하공간: blood vessels
Arachnoid mater 뇌거미막, 뇌지주막
Subarachnoid space 거미막밑공간, 지주막하공간: blood vessels Pia mater 연질막
11 CNS trauma
2) Epidural hematoma 경질막바깥혈종 bleeding between the skull and dura
an accumulation of blood within the epidural space
mostly artery (middle meningeal artery underneath temporal bone)
If untreated, an epidural hematoma is likely to be fatal within 24 to 48 hours.
3) Subdural Hematoma 경질막밑혈종
hemorrhage in the frontal or occipital regions of the head that causes a rapid displacement of the cerebral hemispheres against the inner aspect of the skull
mostly veins within the subdural space.
12
13 CNS trauma
4) Subarachnoid hemorrhage 거미막밑 출혈, 지주막하 출혈
after rupture of a berry aneurysm 딸기동맥류 in the Circle of willis 5) Spinal cord injuries 척추손상
Hyperextension 과다폄, Hyperflexion 과다굽힘 Transection of the spinal cord 척수횡절단
paraplegia (paralysis of the lower body & extremities): 대마비, 하체 및 사지끝의 마비 quadriplegia (paralysis of all four limbs): 사지마비
14 Subarachnoid hemorrhage
15 Circulatory Disorders of the CNS 순환장애
1) Vascular malformations 혈관기형 ~ congenital arteriovenous malformations 동정맥기형
Berry aneurysms 딸기동맥류, atherosclerotic aneurysms 죽상경화성 동맥류, mycotic aneurisms 진균성 동맥류 2) Cerebral hemorrhage 뇌출혈
Berry aneurysms 딸기동맥류, atherosclerotic aneurysms 죽상경화성 동맥류, mycotic aneurisms 진균성 동맥류 2) Cerebral hemorrhage 뇌출혈
Hypertension: weakens vascular wall → Charcot-Bouchard aneurysms 샤르코-부샤르 동맥류 → (rupture) → cerebral hemorrhage
3) Stroke 뇌졸중 (중풍) : ischemia, infarction ischemia: some regions are more sensitive !!
decreased blood flow, hypoxia, watershed infarcts 분수계경색증
the clinical findings associated with regional ischemia reflect the underlying function of the region of the brain 16
17 Hydrocephalus and CSF 물뇌증 및 뇌척수액
Cerebrospinal fluid (CSF) is produced by the choroid plexus 맥락총
Hydrocephalus 물뇌증: a dilation of the ventricular system secondary to increased CSF volume behind a region of obstruction
infancy: expansion of cranium (why?), seizures, optic atrophy, weakness
adults: ↑intracranial pressure → headache, vomiting, papilledema, mental deterioration The obstruction may be relieved by surgical CSF drainage or shunting.
18 Infectious diseases of the CNS 감염질환
Meningitis 수막염 (meninges), encephalitis 뇌염 (cortex), myelitis 척수염 (spinal cord) Bacterial meningitis
pachymeningitis 경수막염 (dura mater, no inflammation in CSF) leptomeningitis 연수막염 (arachnoid and pia mater, infection of CSF)
Tuberculosis meningitis 결핵수막염: usually fatal in 4 to 6 weeks when untreated.
c.f. Pott disease = tuberculous infection of the spine 19 Viral Encephalomyelitis 바이러스뇌척수염
West Nile virus 서부 나일강 열바이러스 → arbovirus, transmitted by mosquito.
Poliomyelitis 회색질척수염 = “소아마비”
Poliovirus (a nonenveloped single-stranded RNA enterovirus)
preferentially infects the anterior horn cells and bulbar motor nuclei of the spinal cord vaccines !!
Rabies 광견병
rhabdovirus from saliva from animal bites
Rabies 광견병
rhabdovirus from saliva from animal bites
the virus infects peripheral nerves → transported to the spinal cord (retrograde axoplasmic flow) painful throat spasm, difficulty swallowing, “hydrophobia 공수 恐 두려울 공 水”
Herpex simplex virus
Measles virus 홍역바이러스 → subacute sclerosing panencephalitis (SSPE) 아급성 경화 범뇌염 20
21
22 Hydrophobia 23
Zoster (Shingle)
Caused by varicella-zoster virus (VZV).
The first exposure to VZV produces varicella (chicken pox).
The virus then becomes latent, and its reactivation in ganglion cells later in life causes zoster (shingles).
The virus travels down the sensory nerve for a single dermatome 피부분절.
It then infects the corresponding epidermis, producing a localized, painful vesicular eruption.
Dermatome?
A dermatome is an area of skin supplied by sensory neurons that arise from a spinal nerve ganglion.
24 Prion Diseases
a group of neurodegenerative conditions characterized by slowly progressive ataxia 실조
dementia 치매
accumulations of fibrillar or insoluble prion proteins
degeneration of neurons, and vacuolization, termed spongiform degeneration Creuzfeldt-Jakob Disease (CJD) in human
similar diseases occur in animals
bovine spongiform encephalopathy (BSE; mad cow disease) PrPc (normal) vs. PrPSC (pathogenic)
→ no difference in amino acid sequence, only differ in conformation !!
All prion diseases are lethal over a span of months to years.
→ no difference in amino acid sequence, only differ in conformation !!
All prion diseases are lethal over a span of months to years.
25 Creuzfledt-Jakob Disease (CJD)
Sporadic, Familial, and Iatrogenic Creutzfeldt-Jakob Disease (sCJD, fCJD, and iCJD) sCJD: the most common human prion disease.
fCJD:mutations in the PRNP gene coding for the prion protein.
iCJD: resulted from transplanting such as cornea and dura mater.
New Variant Creutzfeldt-Jakob Disease (vCJD)
vCJD and the associated bovine spongiform encephalopathy, also known as “mad cow” disease, underscore the interrelatedness of animal and human infectious agents.
presumably contracted by eating the meat of infected animals.
26 27
국내 두번째 '수술감염 CJD' 환자 끝내 사망
연합뉴스 | 입력2013.02.14 06:15 | 수정2013.02.14 10:03 1988년 뇌수술 후 감염…첫 사망환자와 투병과정 유사
(서울=연합뉴스) 김길원 기자 = 뇌수술 과정에서 크로이츠펠트야콥병(CJD)에 감염된 것으로 확인된 국내 두번째 '의인성(醫因性) CJD' 환 자 백모(50) 씨가 최근 사망한 것으로 확인됐다.
14일 의료계와 질병관리본부에 따르면 백 씨는 1988년 5월 뇌실질 부위에 외상을 당해 뇌경막 대용제품인 '라이오듀라(Lyodura)'를 이식한 이후 의인성 CJD 증상을 보여 줄곧 서울과 지방의 병원을 오가며 투병해오다 지난달 27일 숨을 거뒀다.
질병관리본부는 2011년 12월 이 환자가 뇌경막 이식 후 발생한 의인성 CJD(iCJD) 두번째 사례로 확인됐다고 발표한 바 있다.
백 씨는 1988년 당시 학생운동에 참여했다가 머리를 다친 뒤 공무집행방해로 구치소에 있던 중 구토를 호소하다 인근 대학병원에 이송돼 뇌경 막 이식 수술을 받았다는 게 주변 사람들의 설명이다.
하지만 그는 이 수술 이후 눈이 침침해지는 증상을 호소하는 등 의인성 CJD로 의심할만한 상태를 보였던 것으로 알려졌다. 백 씨는 결국 2011년 4월께부터 증상이 걷잡을 수 없이 악화돼 병원에서 말기 치료에 의존해오다 유명을 달리했다.
하지만 그는 이 수술 이후 눈이 침침해지는 증상을 호소하는 등 의인성 CJD로 의심할만한 상태를 보였던 것으로 알려졌다. 백 씨는 결국 2011년 4월께부터 증상이 걷잡을 수 없이 악화돼 병원에서 말기 치료에 의존해오다 유명을 달리했다.
주목할만한 것은 국내 첫 의인성 CJD 환자와 두번째 환자의 투병 기간이나 연령이 비슷하다는 점이다.
첫 환자의 경우 수술 감염 후 23년만인 54세에 사망했고, 두번째 환자인 백 씨도 CJD에 감염된 지 25년만인 50세에 사망했다.
또 사망하기 1년여전부터 증세가 급속도로 악화된 점도 두 환자가 비슷하다.
질병관리본부 관계자는 "전반적으로 CJD 진단을 받은 환자들의 수명이 짧지만 의인성 CJD 환자는 상대적으로 수명이 더 단축되는 편"이라 며 "두번째 환자에 대한 (질병관리본부의) 역학조사에서는 교통사고 때문에 뇌경막 이식 수술을 받은 것으로 안다"고 말했다.
28 Demyelinating disease of the CNS (loss of myelin) 중추신경계의 탈수초질환 1) Metachromatic leukodystrophy 이염성 백색질장애 (MLD)
Deficiency in “arylsulfatase”.
Deficiencies result in an accumulation of
sulfatides in Schwann cells and oligodendrocytes
→ demyelination
2) Krabbe disease 크라베질환 (Globoid cell leukodystrophy 구상세포 백색질장애) Deficiency of “galactocerebroside β galactosidase” in oligodendrocytes.
presence of “globoid cells 구상세포”, which are macrophage containing undigested galactocerebroside 29 Demyelinating disease of the CNS (loss of myelin)
3) Adrenoleukodystrophy 부신백색질장애 (ALD)
an inherited demyelinating disease and impairment of adrenal function.
caused by mutation in ABCD1 (ALDP) in Xq28
high levels of saturated very-long-chain fatty acid 포화된 매우 긴 사슬 지방산 (VLCFA) → loss of myelinated axons and oligodendrocyte.
treatment: “Lorenzo’s oil” (mixture of oleic acid and erucic acid) → inhibits elongation of saturated fatty acids in the body.
30
treatment: “Lorenzo’s oil” (mixture of oleic acid and erucic acid) → inhibits elongation of saturated fatty acids in the body.
30
Lorenzo Odone
Lorenzo Odone, who died on Friday, the day after his 30th birthday, became famous throughout the world with the release, in 1992, of the film Lorenzo's Oil, starring Susan Sarandon and Nick Nolte.
At the time that the film was made, Lorenzo was 14 and had been suffering for eight years from
adrenoleukodystrophy (ALD) a genetic disease, affecting mainly boys, which usually results in brain failure and, The film dramatised the attempts by his parents, Augusto and Michaela Odone (played by Nolte and Sarandon), to find an effective treatment, a quest which culminated in the invention of "Lorenzo's oil", a derivative of olive and
rapeseed oils and the first agent to have demonstrated a therapeutic effect by halting the destruction, by the disease, of the myelin sheathing of the nervous system.
The treatment was patented by Augusto Odone, and a study published in 2005, based on research with 84 boys, demonstrated its efficacy in preventing the onset of the disease's symptoms for a majority of boys diagnosed early with ALD. This discovery came too late for Lorenzo Odone, who was already suffering from the irreversible
neurological effects of the disease.
Augusto Odone and his wife went further, however, founding a charity called the Myelin Project, an international scientific body which seeks to promote research into those diseases which destroy myelin, the white matter of the central nervous system without which the brain cannot transmit messages to other parts of the body. The goal is to bring hope to those suffering from conditions such as multiple sclerosis and the leukodystrophies (of which ALD is 31
32 Demyelinating disease of the CNS (loss of myelin) Multiple Sclerosis (MS) 다발경화증
A chronic demyelinating disease, young adults, F>M (2:1) Cause: genetic, immune, infections...
Demyelinated plaque, multiple scars Symptoms
the accumulation of demyelinating lesions in different regions of the brain at different periods !! → relapsing- remitting is common.
loss of vision in one eye, blurred vision, vertigo, weakness or numbness of legs → paralysis, dysarthria, severe visual defects, dementia
33 Storage diseases 축적증
loss of vision in one eye, blurred vision, vertigo, weakness or numbness of legs → paralysis, dysarthria, severe visual defects, dementia
33 Storage diseases 축적증
Tay-sachs disease 테이-삭스 질환
manifests by 6 months of age, defects in hexosaminidase A → accumulation of gangliosides in CNS → cherry red spot in retina.
Gaucher disease 고쉐병
defects in glucocerebosidase → accumulation of glucocerebroside in macrophages.
Niemann-Pick disease 니만-픽 질환
deficiency of sphingomyelinase → ↑intraneuronal storage of sphingomyelin → retinal degeneration, cherry red spot in macula
Inborn neuronal disorders Phenylketouria
Cretinism
Wilson disease: mutation in WD gene → defective copper metabolism 34 Neurodegenerative disease 신경변성질환
1) Parkinson Disease (PD) 파킨슨 질환
loss of pigmented, dopaminergic neurons in the substantia nigra 흑색질 and locus ceruleus 청색반점, 청반 Lewy bodies 루이체 (= aggregates of α-synuclein)
Symptoms: movement disorders
slow movement, muscular rigidity, tremor of the distal extremities, expressionless (masklike) face, ↓swallowing ( → drooling)
Treatment: levodopa (precursor of dopamine) 35
36 37
38 Neurodegenerative disease
2) Amyotrophic Lateral Sclerosis (ALS) 근육위축가쪽경화증, 근육위축측삭경화증
= Lou Gehrig's disease 루게릭병
degeneration of motor neurons, progressive deterioration of the extremities
cause unknown, but in some case, superoxide dismutase 1 (SOD1) gene mutation
2) Amyotrophic Lateral Sclerosis (ALS) 근육위축가쪽경화증, 근육위축측삭경화증
= Lou Gehrig's disease 루게릭병
degeneration of motor neurons, progressive deterioration of the extremities
cause unknown, but in some case, superoxide dismutase 1 (SOD1) gene mutation
"gain of function" mutation !!
Symptoms
begins as weakness and wasting of the muscles of the hand, often accompanied by painful cramps of the arm fasciculations 섬유다발수축, 섬유속성연축 that do not results in limb movement
total disability, unintelligible speech, respiratory weakness dementia is uncommon
39 Neurodegenerative disease
3) Trinucleotide repeat expansion syndromes 삼뉴클레아타이드 반복 확장 증후군
① Huntington Disease (HD) 헌팅튼병
expansion of "CAG" repeats in the coding region of the HD gene
autosomal dominant, HD: huntingtin, unknown function
pathology: cortex atrophy
symptoms: intellectual deterioration
② Inherited Spinocerebellar Ataxias: Friedreich Ataxia: Friedrich ataxia (FA) 유전적인 척수소뇌 운동실조증: 프리이드라이히 운동실조
expansion of "GAA" repeats in the frataxin gene 40 Neurodegenerative disease
4) Alzheimer disease (AD) 알츠하이머병 The most common cause of dementia Genetic factors
ApoE, presenilin-1, presenilin-2…
Senile plaques 노인성 플라그: aggregation of Aβ
Amyloid precursor protein (APP) → Aβ (insoluble) Neurofibrillary tangles (NFT) 신경원섬유성 농축체
aggregates of tau protein, which is associated with microtubule
Neurofibrillary tangles (NFT) 신경원섬유성 농축체
aggregates of tau protein, which is associated with microtubule Symmetrical cortex atrophy 대칭적인 위축
Symptoms: a gradual loss of memory and cognitive function, difficulty with language, and behavioral changes.
41
42 Tumors of the CNS 종양
CNS neoplasms cannot be readily categorized into benign versus malignant, 43
44 Peripheral Nervous System 45 Characteristics of PNS
Cranial nerves (I ~ XII) 뇌신경
Dorsal/ventral spinal roots 후/전 척수 신경근 Spinal nerves (31 pairs) 척수신경
Ganglia 신경절
Somatic motor 체성운동, somatic sensory 체성감각, visceral sensory 내장감각, autonomic fibers 자율신경감각 myelinated (larger 1~20 µM in diameter)
vs.
unmyelinated (smaller 0.4~2.4 µM)
Schwann cell 슈반세포 : ensheath both myelinated and unmyelinated fibers → axon determines whether the ensheathing Schwann cell differentiates into a myelin forming cell
46 Myelinated vs. Unmyelinated fiber 47 Reactions to injury 손상에 대한 반응
Unlike CNS, PNS has axonal regeneration & remyelination capability
axonal degeneration 축삭변성 ~ usually restricted to the distal axon 원위축삭
→ “dying-back neuropathies 역행사 신경병증" (= distal axonopathy) direct injury to Schwann cell
→ segmental demyelination
Axonal neuropathy 축삭 신경병증 (80~90%) Demyelinated neuropathy 탈수초 신경병증
→ Muscle weakness, muscle atrophy, altered sensation, autonomic dysfunction...
Demyelinated neuropathy 탈수초 신경병증
→ Muscle weakness, muscle atrophy, altered sensation, autonomic dysfunction...
48 Peripheral Neuropathy
1. Diabetic neuropathy 당뇨신경병증 distal sensory polyneuropathy
2. Guillain-Barré syndrome 길랭-바레 증후군 (Acute Inflammatory Demyelinating Polyneuropathy 급성 염증성 탈수초 다발신 경병증)
an acquired, immune-mediated neuropathy, acute symmetric paralysis that begins distally and ascends proximally 3. Charcot-Marie-Tooth (CMT) disease 샤르코-마리-투스병
hereditary, slowly progressive distal sensorimotor polyneuropathy, childhood or early adult 49
50
51 Tumors of the PNS 말초신경계 종양 Schwannoma
Neurofibroma = Schwann cell + perineurial-like cells + fibroblasts Malignant Peripheral Nerve Sheath Tumor (MPNST)
mostly from "neurofibromatosis"
52
1 Chapter 30. The Eye 2
3 4
5 Orbit 안와
Exophthalmos 안구돌출
bilateral, Grave disease (hyperthyroidism) c.f. Proptosis 돌출 ~ unilateral protrusion Corneal ulceration 각막궤양
mostly caused by herpes simplex virus type 1 contact lens
6 Lens 수정체
Cause: aging, diabetes, ↓riboflavin, ↓tryptophan, toxins, drugs (e.g. corticosteroids), UV light…
Symptoms: blurry vision, ↓contrast, photophobia Treatment: Surgery
7
8 Retina 망막
1) Retinal hemorrhage 망막출혈
Cause: hypertension, diabetes mellitus, central retinal vein occlusion...
2) Occlusive retinal vascular disease 폐쇄성 망막 혈관병
Vascular occlusion results from thrombosis, embolism, stenosis (as in atherosclerosis), vascular compression, vasoconstriction...
Central retinal artery occlusion Cherry-red spot → blindness Central retinal vein occlusion
Vision is disturbed but may recover surprisingly well.
Cotton-wool spots
3) Hypertensive retinopathy 고혈압성 망막병증 9
9
10 The Retina
4) Diabetic retinopathy 당뇨병 망막병증
ocular symptoms occur in 20% to 40% of diabetics
patients whose diabetes in better controlled develop retinopathy less frequently.
Retinal ischemia can account for most features of diabetic retinopathy
Background (non-proliferative) diabetic retinopathy → Proliferative diabetic retinopathy 11
12 The Retina
5) Retinal Detachment 망막박리
the retina separates from the retinal pigment epithelium 망막색소상피 when fluid (liquid vitreous, hemorrhage, or exudate) accumulates within the potential space between these structures.
After they separate in a retinal detachment, oxygen and nutrients that normally reach the outer retina from the choroid must diffuse across a greater distance. This situation causes the photoreceptors to degenerate.
13 The Retina
6) Retinitis Pigmentosa 망막색소변성
a generic term that refers to a variety of bilateral, progressive, degenerative retinopathies characterized by night blindness
constriction of peripheral visual fields
loss of retinal photoreceptors (rods and cones) pigment accumulation within the retina
misnomer because there is no inflammation !
contraction of visual field → tunnel vision → blindness 14 The Retina
7) Macular Degeneration 황반변성 Cause
age, drug (e.g. chrloroquine), genetic (CFH gene) Mostly age-related
Age-related macular degeneration currently affects almost 2 million people in the United States
the most common cause of blindness among persons of European descent older than 65 years of age.
“wet” and “dry” macular degeneration
the most common cause of blindness among persons of European descent older than 65 years of age.
“wet” and “dry” macular degeneration 15 Optic nerve 시각신경
1) Optic nerve head (optic disc) edema = papilledema 시각신경유두부종 swelling of the optic nerve
cause: increased intracranial pressure 2) Optic atrophy 시각신경위축
thinning of optic nerve
Drugs such as ethambutol and isoniazid can also cause optic atrophy.
Leber hereditary optic neuropathy 레버씨선천성시신경
Multiple mutations in the mitochondrial genome are associated 16 Glaucoma 녹내장
an optic neuropathy accompanied by a characteristic excavation of the optic nerve head and progressive loss of visual field sensitivity.
Cause: intraocular pressure (ocular hypertension)
however, increased intraocular pressure does not necessarily cause glaucoma, and not all patients with glaucoma have elevated intraocular pressure.
failure of balance between the production and drainage of the aqueous humor normal: 10 ~ 20 mmHg
Pressure-induced degeneration changes in the retina and optic nerve
→ vision impairment
congenital - developmental anomalies
primary open-angle glaucoma: most common. Individuals with diabetes mellitus and myopia have an increased risk primary closed-angle glaucoma:
secondary: unilateral 17
18
19 Ocular neoplasms 눈의 신생물
Malignant melanoma 악성흑색종: from melanocytes in the uvea 포도막
Retinoblastoma 망막모세포종: from immature neurons (childhood), loss of Rb gene
Malignant melanoma 악성흑색종: from melanocytes in the uvea 포도막
Retinoblastoma 망막모세포종: from immature neurons (childhood), loss of Rb gene
