Nervous system Flashcards
1
Q
- Pathology of raised intracranial pressure:
CEREBRAL EDEMA general + morphology
A
= accumulation of excess fluid within the brain parenchyma
MORPHOLOGY:
- flattened gyri
- narrow sulk
- compressed ventricular cavities
- softer brain
- herniation
2
Q
- Pathology of raised intracranial pressure:
CEREBRAL EDEMA vasogenic edema
A
- occurs when integrity of BBB is disrupted
- increased vascular permeability ⇒ fluid to IC space
- localized or generalized
3
Q
- Pathology of raised intracranial pressure:
CEREBRAL EDEMA cytotoxic edema
A
- neuronal, glial, endothelial cell membrane injury ⇒ increased IC fluid
- due to generalized hypoxic/ischemic insult or exposure to toxins
- ischemia ⇒ cells can’t supply sodium pump ⇒ loss of membrane potential ⇒ inflow of water
4
Q
- Pathology of raised intracranial pressure:
SUBFALCINE HERNIATION
A
- expansion of cerebral hemispheres displace the cingulate gyrus under the edge of falx cerebri
- associated with compression of branches of ACA ⇒ ischemia of anterior cerebrum
5
Q
- Pathology of raised intracranial pressure:
TRANSTENTORIAL HERNIATION
A
- medial aspect of temporal lobe compressed against free margin of tentorium cerebelli
⇒ CN III compromised ⇒ pupillary dilation + blown pupil - PCA compressed ⇒ ischemia to visual cortex
+ Duret hemorrhage in pons and midbrain
6
Q
- Pathology of raised intracranial pressure:
TONSILLAR HERNIATION
A
- displacement of cerebellar tonsils through foramen magnum
⇒ life-treathening bc compromises vital respiratory and cardiac centers in medulla
7
Q
- Pathology of raised intracranial pressure:
HYDROCEPHALUS pathophysiology
A
= increase in CSF volume within ventricular system
- occur as a consequence of impaired flow or impaired resorption of CSF, or overproduction of CSF
8
Q
- Pathology of raised intracranial pressure:
HYDROCEPHALUS classification
A
- Communicating
- no blockage
- decreased CSF resorption
- meningitis ⇒ fibrotic tissue in arachnoid mater
- whole ventricular system dilates - Non-communicating
- obstruction of CSF flow
- dilation of part of ventricular system - Hydrocephalus ex vacuo
- atrophy of brain due to infarct or degenerative disease
- dilation of ventricular system ⇒ increase in CSF volume
Hydrocephalus internus or externus
9
Q
- Pathology of raised intracranial pressure:
HYDROCEPHALUS clinical features
A
Adults:
- develop after fusion of sutures ⇒ associated with expansion of ventricles + increased ICP
Children:
- develops before closure of cranial sutures ⇒ enlargement of head
10
Q
- Congenital malformations of central nervous system:
NEURAL TUBE DEFECTS
A
- failure of neural tube to close or reopen after closure
- characterized by abnormalities involving neural tissue, meninges and overlying bone and soft tissues
11
Q
- Congenital malformations of central nervous system:
SPINA BIFIDA OCCULTA
A
- neural tube defect
- asymptomatic bony defect
- posterior end affected
12
Q
- Congenital malformations of central nervous system:
MENINGOCELE
A
- neural tube defect
- flattened, disorganized segment of spinal cord + overlying meningeal outpuching
- posterior end affected
13
Q
- Congenital malformations of central nervous system:
MYELOMENINGOCELE
A
- neural tube defect
- extension of CNS tissues through defect in vertebral column ⇒ abnormal spinal cord
- mostly in lumbosacral region
- motor and sensory deficits in lower extremities and problems with bowel and bladder control
14
Q
- Congenital malformations of central nervous system:
ANENCEPHALY
A
- neural tube defect
- malformation of the anterior end
- absence of brain and top of skull
15
Q
- Congenital malformations of central nervous system:
ENCEPHALOCELE
A
- neural tube defect
- diverticulum of malformed CNS tissue extending through defect in cranium
- mostly occipital region and posterior fossa
16
Q
- Congenital malformations of central nervous system:
MEGAENCEPHALY AND MICROENCEPHALY
A
- forebrain malformation
- volume of brain abnormally large or small
- occur with chromosome abnormalities, fetal alcohol syndrome and HIV-1 infection in utero
⇒ decreased number of neurons
17
Q
- Congenital malformations of central nervous system:
LISSENCEPHALY AND PACHGYRIA
A
- forebrain malformation
- absence of normal gyration ⇒ smooth surface brain
- cortex thickened and 4-layered
- single gene defect
18
Q
- Congenital malformations of central nervous system:
POLYMICROGYRIA
A
- forebrain malformation
- increased number of irregularly formed gyri ⇒ irregular bumpy or cobblestone-like surface
- changes can be local or widespread
19
Q
- Congenital malformations of central nervous system:
HOLOPROSENCEPHALY
A
- forebrain malformation
- disruption of normal midline patterning
- mild form: absence of olfactory bulb
- severe form: brain is not divided into hemispheres or lobes ⇒ cyclopia
20
Q
- Congenital malformations of central nervous system:
CHIARI 1 MALFORMATION
A
- posterior fossa malformation
- cerebellar tonsils extend through foramen magnum
⇒ obstruction of CSF flow + compression of medulla
⇒ headache + cranial nerve deficits
21
Q
- Congenital malformations of central nervous system:
ARNOLD-CHIARI MALFORMATION
A
- posterior fossa malformation
- small posterior fossa + misshapen midline cerebellum with downward extension of vermis through foramen magnum
⇒ hydrocephalus + lumbar myelomeningocele
22
Q
- Congenital malformations of central nervous system:
DANDY-WALKER MALFORMATION
A
- posterior fossa malformation
- enlarged posterior fossa
23
Q
- Congenital malformations of central nervous system:
SPINAL CORD MALFORMATIONS
A
MORPHOLOGY:
- discontinuous or confluent expansion of ependyma-lined central canal (hydromyelia)
- formation of fluid-filled cleft-like cavity (syringomyelia)
- may develop secondary to alteration in CSF flow by tumor or trauma
- associated with destruction of grey and white matter + surrounded by reactive gliosis
- cervical spinal cord mostly affected
24
Q
- Cerebrovascular diseases:
GENERAL
A
= abnormality of the brain caused by:
- thrombotic occlusion ⇒ infarct
- embolic occlusion ⇒ infarct
- vascular rupture ⇒ intracranial hemorrhage
3 causes of ischemia/hypoxia:
⇒ generalized cerebral hypoxia/ischemia
⇒ infarct
⇒ vasculitis
25
114. Cerebrovascular diseases:
| GLOBAL CEREBRAL ISCHEMIA etiology
- when generalized reduction of cerebral perfusion ⇒ systolic pressure <55mmHg
- decrease in O2 saturation/ increase in CO2 saturation
26
114. Cerebrovascular diseases:
| GLOBAL CEREBRAL ISCHEMIA clinical features
MILD:
- transient postischemic confusional state ⇒ complete recovery
- irreversible CNS changes ⇒ pyramidal cells of hippocampus, Purkinje cells, pyramidal neurons in neocortex most susceptible
SEVERE:
- widespread neuronal death ⇒ neurological impairment and comatose
- brain dead
BORDERZONE INFARCT:
- zone between major cerebral arteries suffers hypo perfusion ⇒ hemorrhagic infarct(encephalo malacia rubra)
27
114. Cerebrovascular diseases:
| GLOBAL CEREBRAL ISCHEMIA morphology
- swollen brain ⇒ wide gyri, narrow sulci
- poor demarcation between white and grey matter
- herniation
EARLY (12-24h):
⇒ red neurons, eosinophilia, neuronal pyknosis and karyorrhexis, neutrophilia
SUBACUTE (24h-2w):
⇒ necrosis, macrophages, vascular proliferation, reactive gliosis
REPAIR (>2w):
⇒ removal of necrotic tissue
28
114. Cerebrovascular diseases:
| GLOBAL CEREBRAL ISCHEMIA transient ischemic attack
```
= episode of neurologic dysfunction caused by ischemia without infarction ("mini stroke")
- due to disrupted cerebral blood flow
- symptoms: paralysis, weakness
⇒ resolve after minutes-hours
- no morphological changes
- warning sign for infarct
```
29
114. Cerebrovascular diseases:
| FOCAL CEREBRAL ISCHEMIA classification
1. Ischemic infarct - white infarct
- artery occlusion
2. Hemorrhagic infarct - red infarct
- repercussion of ischemic infarct
- vein obstruction
- borderzone infarct
30
114. Cerebrovascular diseases:
| FOCAL CEREBRAL ISCHEMIA etiology + risk factors
Occlusion of cerebral artery due to:
1. Atherosclerosis ⇒ in situ thrombosis (basilar a., MCA)
2. Embolism
- from bifurcation of carotids
- from mural thrombi
- paradoxial
RISK FACTORS:
1. hypertension
2. diabetes mellitus
3. hypertriglyceremia
4. atherosclerosis
5. atrial fibrillation
6. transient ischemic attack
31
114. Cerebrovascular diseases:
| VASCULITIS
- may involve cerebral arteries ⇒ infarct
- inflammatory disorder, involves medium-sized parenchymal and subarachnoidal vessels
- chronic inflammation + destruction of vessel wall
- symptoms: cognitive dysfunction
- treatment: steroid and immunosuppression
- infectious arteritis can be caused by toxoplasma, aspergillosis, CMV encephalitis
32
114. Cerebrovascular diseases:
| LACUNAR INFARCTS
= hypertensive cerebrovascular disease
- HT ⇒ hyaline arteriolar sclerosis of deep arterioles of basal ganglia
- walls become weaker + more vulnerable to rupture
- small localized infarcts - few mm wide, mostly in deep grey matter + internal capsule
- clinically silent or neurologic impairment
33
114. Cerebrovascular diseases:
| FOCAL CEREBRAL ISCHEMIA morphology
Non-hemorrhagic infarct;
0-6h: normal tissue
6-12h: red neurons
12-48h: tissue is pale, soft, swollen + neutrophilia
2-10d: brain is gelatinous + friable, edematous
10d-3w: tissue liquefies, macrophages
3w-months: astrocyte + cytoplasmic enlargement regresses
34
115. Intracranial hemorrhage:
| CAUSES
⇒ hypertension
⇒ vascular malformation
⇒ bleeding disorder
⇒ trauma
35
115. Intracranial hemorrhage:
| APOPLEXIA
= intracerebral hemorrhage
- cause: HT
- rupture by:
* arteriolosclerosis ⇒ narrowing of lumen, fibrinoid material deposition in vessel wall
* Charcot-Bouchard ⇒ small micro aneurysm
36
115. Intracranial hemorrhage:
| HEMORRHAGE FROM VASCULAR MALFORMATION
TYPES:
1. arteriovenous malformation
- abnormal connection of arteries to veins
- loss of capillaries ⇒ increased pressure ⇒ prone to rupture
- seizure disorder, intracerebral hemorrhage, subarachnoid hemorrhage
2. cavernous angiomas
3. capillary telangiectasias
4. venous angiomas
37
115. Intracranial hemorrhage:
| PURPURA CEREBRI
```
= small bleedings in brain
CAUSES:
- thrombopathy
- coagulopathy
- vasculopathy
```
38
115. Intracranial hemorrhage:
| SUB-EPENDYMAL HEMORRHAGE
= bleeding under ependyma
- in immature babies ⇒ vasculature not well developed ⇒ sensitive to changes in pH and PaO2
- superimposed IRDS ⇒ low PaO2 ⇒ hypoxia ⇒ hemorrhage
39
115. Intracranial hemorrhage:
| SUBARACHNOID HEMORRHAGE
= bleeding between arachnoid mater and pia mater
- cause: rupture of berry aneurysm (disorder of ECM, polycystic kidney disease cause berry aneurysm)
- symptom: sudden, excrusiating headache + rapid unconsiousness
40
115. Intracranial hemorrhage:
| SUBDURAL HEMORRHAGE
= tear in bridging veins ⇒ hemorrhage between dura mater and arachnoid mater
- cause: trauma
- can be chronic in alcoholics (fall a lot)
41
115. Intracranial hemorrhage:
| EPIDURAL HEMORRHAGE
= tear in middle meningeal artery ⇒ separation of dura from skull
- cause: fracture of skull
- can compress brain surface
- symptom: lucid for many hours, neurological signs
42
116. Degenerative diseases and dementias:
| DEFINITIONS
Degenerative disease=
- progressive cellular degeneration of neurons ⇒ deterioration of brain function
Dementia=
- memory impairment + cognitive deficits with normal level of consciousness
43
116. Degenerative diseases and dementias:
| ALZHEIMER DISEASE general
- slow loss of intellectual function + alteration of mood and behavior
⇒ progressive disorientation, memory loss, aphasia
⇒ disabled, mute, immobile
- increasing incidence with age
44
116. Degenerative diseases and dementias:
| ALZHEIMER DISEASE pathogenesis
- sporadic or familial
FAMILIAL:
- accumulation of Beta amyloid (APP cleaved by beta-site of enzyme + gamma-seretase)
- mutations in APP ⇒ earlier onset of disease
- Down syndrome ⇒ APP located on chromosome 21
- allele of apolipoprotein E4 ⇒ increase risk + earlier onset
- SORL1 protein deficiency ⇒ late onset ⇒ alter intracellular trafficking of APP
⇒⇒ accumulations alter neurotransmission + are toxic to neurons and synapses + local inflammatory response to plaque
⇒ plaques, neurofibrillary tangles, neuronal loss
45
116. Degenerative diseases and dementias:
| PARKINSONS DISEASE general
- death of dopamine- containing cells in substansia nigra
| - diagnosis: no etiology + response to L-DOPA treatment
46
116. Degenerative diseases and dementias:
| PARKINSON DISEASE pathogenesis
- sporadic or AD/AR
- AD: alpha-synuclein mutation
- Lewy body = intramural inclusion of alpha-synuclein ⇒ shows defective degradation of the protein in the proteasome
47
116. Degenerative diseases and dementias:
| PARKINSONS DISEASE clinical features
Parkinsonism=
- diminished facial expression
- stooped posture
- slowness of voluntary movement
- festinating gait
- rigidity and tremor
- progresses over 10-15 years
- develop dementia
48
116. Degenerative diseases and dementias:
| HUNTINGTON DISEASE general
- inherited AD neurodegenerative disease
- age: 40-50s
- progressive movement disorders and dementia caused by tandem repeats
- death in about 15 years
49
116. Degenerative diseases and dementias:
| HUNTINGTON DISEASE pathogenesis
- tandem repeat CAG mutation in gene 4p16.3 ⇒ Huntingtin protein
- the larger the number of repeats ⇒ the earlier onset of the disease
* the mutated Huntingtin protein binds to and sequesters transcription factors ⇒ reduced synthesis of proteins
* mutated Huntingtin protein causes functional abnormalities in mitochondria ⇒ neurodegeneration
50
116. Degenerative diseases and dementias:
| HUNTINGTON DISEASE clinical features
- Huntington chorea: involuntary jerky movement
- may develop parkinsonism
- forgetfulness + emotional disorders ⇒ dementia
51
116. Degenerative diseases and dementias:
| AMYOTROPHIC LATERAL SCLEROSIS general
- degeneration of motor neurons in ventral horn of spinal cord
- sensory systems and cognitive functions unaffected
- lateral sclerosis= degeneration of corticospinal tracts
- age: 50s
52
116. Degenerative diseases and dementias:
| AMYOTROPHIC LATERAL SCLEROSIS etiology
- familial AD or sporadic
- Mutation in gene superoxide dismutase SOD1 on chromosome 21
- missense mutations ⇒ misfiling of protein ⇒ apoptosis
53
116. Degenerative diseases and dementias:
| AMYOTROPHIC LATERAL SCLEROSIS clinical features
```
Loss of upper motor neurons:
⇒ paresis
⇒ hyperreflexia
⇒ spasticity
⇒ positive Babinski sign
Loss of lower motor neurons:
⇒ denervation of muscular targets with symptoms of muscular atrophy
⇒ weakness
⇒ fasciculation
```
Early symptoms:
- weakness of hands, cramping of arms and legs
Late symptoms:
- muscle mass + strength decreases, involuntary contractions
54
117. Infections of the nervous system:
| BRAIN INFECTIONS ROUTES
1. Hematogenous spread
2. Direct implantation (post-traumatic, iatrogenic)
3. Local extension
4. Peripheral nerves
55
117. Infections of the nervous system:
| MENINGITIS classification
1. Infectious meningitis
- acute pyogenic meningitis
- aseptic meningitis
- chronic meningitis
2. Non-infectious meningitis
- spread of cancer
- drugs
- inflammatory lesions
56
117. Infections of the nervous system:
| ACUTE PYOGENIC MENINGITIS
```
BACTERIA:
- neonates: E.coli, S.agalactiae
- adolescents: N.meningitides
- elderly: S.pneumoniae, L.monocytogenes
SYMPTOMS:
- headache
- photophobia
- irritability
- clouding of consciousness
- neck stiffness
- Lumbar puncture ⇒ increased pressure, neutrophilic, elevated protein, reduced glucose
- untreated ⇒ fatal
```
57
117. Infections of the nervous system:
| ASEPTIC MENINGITIS
```
VIRUS:
- enterovirus
- HSV-2
CLINICAL FEATURES:
- less severe + self-limited
- increased lymphocytes
- protein elevation moderate
- glucose normal
- brain swelling
```
58
117. Infections of the nervous system:
| CHRONIC MENINGITIS
TUBERCULOUS MENINGITIS:
- generalized symptoms: malaise, headache, mental confusion, vomiting
- high protein, normal glucose
- tuberculoma
- leads to arachnoid fibrosis, hydrocephalus
NEUROSYPHLIS:
- tertiary stage of syphilis
- invasion of brain by T.pallidum
NEUROBORRELIOSIS:
- Borrelia burgdorferi
- symptoms: aseptic meningitis, facial nerve palsies, encephalopathy, polyneuropathies
59
117. Infections of the nervous system:
| ENCEPHALITIS general
= acute inflammation of the brain
| - causative agents: bacterial, viral, fungal
60
117. Infections of the nervous system:
| BACTERIAL ENCEPHALITIS
- can spread directly to brain
| - syphilis ⇒ neurosyphilis ⇒ encephalitis
61
117. Infections of the nervous system:
| ARBOVIRUS
- cause epidemic encephalitis
| - generalized neurologic symptoms ⇒ seizures, confusion, delirium, stupor, coma, reflex assymetry, ocular palsies
62
117. Infections of the nervous system:
| HSV-1
- causes encephalitis
- any age group, mostly children + young adults
Symptoms:
⇒ alterations in mood
⇒ memory
⇒ behavior
63
117. Infections of the nervous system:
| VZV
- chickenpox ⇒ latent in sensory ganglia ⇒ shingles
| - immunosuppressed patients ⇒ encephalitis
64
117. Infections of the nervous system:
| CYTOMEGALOVIRUS
- fetuses + immunocompromised
| - in-utero infection ⇒ periventricular necrosis, microcephaly
65
117. Infections of the nervous system:
| POLIOVIRUS
- enterovirus ⇒ paralytic poliomyelitis
- symptoms:
* gastroenteritis
* damages motor neurons
* flaccid paralysis
* death from paralysis of respiratory muscles
* post-polio syndrome ⇒ decreased muscle bulk and pain
66
117. Infections of the nervous system:
| RABIES
- causes encephalitis
- virus enters CNS by ascending along peripheral nerves
- symptoms:
* flu-like (malaise, headache, fever)
* extraordinary CNS excitability
* periods of alternating mania and stupor
* coma + death
67
117. Infections of the nervous system:
| HUMAN IMMUNODEFICIENCY VIRUS HIV
- Aseptic HIV-1 meningitis
- HIV-1 meningoencephalitis
⇒ AIDS-dementia complex
⇒ chronic inflammation with microglial nodules
- Vacuolar myelopathy
⇒ spinal cord tracts
68
117. Infections of the nervous system:
| FUNGAL ENCEPHALITIS
1. Candida albicans ⇒ multiple microabscesses
2. Mucor ⇒ mostly in diabetics with ketoacidosis
3. Aspergillus fumigatus ⇒ widespread septic hemorrhagic infarctions
4. Cryptococcus neoformans ⇒ often associated with AIDS
69
117. Infections of the nervous system:
| PROTOZOAL ENCEPHALITIS
TOXOPLASMOSIS:
- connatal:
* multifocal nectosis
* calcification
* hydrocephalus
- immunocompromised:
* necrotizing endephalitis
70
117. Infections of the nervous system:
| HELMINTH ENCEPHALITIS
ECHINOCOCCUS:
⇒ granulosus + multilocularis
T.SOLIUM :
⇒ cysticerosis
71
118. Prions:
| PRION DISEASES pathogenesis
= misfolded abnormal forms of a normal cellular protein, PrPc
⇒ acts as infectious agent ⇒ propagates + injures cells near by
- PrPc ⇒ PrPsc ⇒ resistant to protease digestion ⇒ initiate similar transformation to other PrPc molecules
⇒ accumulation of PrPsc in neural tissue ⇒ cell injury
PrPc: alpha-helix, soluble, non-infectious
PrPsc: beta-sheat, insoluble, infectious
72
118. Prions:
| CREUTZFELDT-JAKOB DISEASE
- manifests as rapidly progressive dementia
- sporadic / familial
- peak incidence age: 70s
- symptoms:
* memory and behavior changes
* dementia
- uniformly fatal, duration 7months
73
118. Prions:
| VARIANT CREUTZFELDT-JAKOB DISEASE
- affects young adults
- symptoms:
* behavior changes
* progresses more slowly
- consequence of exposure to prion disease of cattle, bovine spongiform encephalopathy
- similar pathologic appearance than other CJDs - spongiform change + absence of inflammation
74
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
CNS AND PNS MYELIN
```
CNS MYELIN:
- multiple layers of oligodendrocytes
- 1 oligodendrocyte ⇒ processes to many different axons
- internodes + nodes of Ranvier
- dominant in white matter
PNS MYELIN:
- made by Schwann cells
- each cell contract to only 1 internode
- specialized proteins + lipids
```
75
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
DEMYELINATING DISORDERS
- acquired diseases
- characterized by damage to previously normal myelin
- Diseases:
* multiple sclerosis (immune-mediated injury)
* progressive multifocal leukoencephalopahty (viral infection of oligodendrocytes)
76
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
DYSMYELINATION
- characterized by defective structure and function of myelin sheaths
- associated with mutations affecting proteins required for formation of normal myelin or in mutation affecting synthesis/degradation of lipids
- leukodystrophies
77
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
MULTIPLE SCLEROSIS general + etiology
- autoimmune inflammatory disease with demyelination
- age: 15-45 years old
- more in women 2:1
- relapsing and remitting episodes
ETIOLOGY:
- combination of environmental + genetic factors ⇒ loss of tolerance to self proteins
78
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
MULTIPLE SCLEROSIS clinical features
- pattern of relapsing-remitting disease ⇒ gradual accumulation of increasing neurologic deficits
- Visual impairment ⇒ unilateral
- Brain stem symptoms ⇒ cranial nerve signs, ataxia
- Spinal cord symptoms ⇒ motor and sensory impairment of trunk + limbs, spasticity, difficulty with bladder control
- Cognitive function
79
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
MULTIPLE SCLEROSIS morphology
MACROSCOPIC:
- grayish plaques in white matter
- mostly periventricular
MICROSCOPIC:
- active: macrophages
- inactive: no macrophages
- active plaque: fragmentation of myelin, preserve axon, luxol in macrophages
- subacute plaque: myelin loss, PAS positive, astrocytosis, perivascular lymphocytic infiltrate
- inactive plaque: no inflammation, no myelin
- on periphery ⇒ iron deposits
- shadow plaque: between normal and affected are ⇒ thin myelin
80
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
MULTIPLE SCELROSIS 4 patterns
1. Classic ⇒ Charcot
2. Acute ⇒ Marburg, aggressive
3. Neuromyelitic optica ⇒ Devic syndrome, affects optic nerve + spinal cord
4. Concentric sclerosis ⇒ Balo, demyelinated tissues form concentric layers
81
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
POST INFECTIOUS DEMYELINATION
- not related to direct spread of infectious agent but immune response to pathogen antigen ⇒ cross react with myelin antigens
1. Acute disseminated encephalomyelitis
- symptoms after week or two after infection
- diffuse brain involvement ⇒ headache, lethargy, coma
- progresses rapidly ⇒ fatal
2. Acute necrotizing hemorrhagic encephalomyelitis
- affects young adults + children
82
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
CENTRAL PONTINE MYELINOLYSIS
- nonimmune process
- loss of myelin in center of pons after rapid correction of hyponatremia
- causes: alcoholism + severe electrolyte imbalance
- symptoms:
* rapidly evolving quadriplegia
83
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
LEUKODYSTROPHIES
- inherited dysmyelinating diseases
- caused by abnormal myelin synthesis or turnover
- some involve lysosomal enzymes or peroxisomal enzymes
- some involve mutations in myelin proteins (AR)
CLINICAL FEATURES:
- diffuse involvement of white matter ⇒ deterioration in motor skills, spasticity, hypotonia and ataxia
84
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
HYPOGLYCEMIA
- resemble global hypoxia (mostly evident in hippocampus)
| - Purkinje cells spared
85
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
HYPERGLYCEMIA
- found in inadequately controlled DM + ketoacidosis or hyperosmolar coma
- symptom:
* confusion
* stupor
* coma
- must be corrected gradually (otherwise severe central edema)
86
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
HEPATIC ENCEPHALOPATHY
- decreased hepatic function ⇒ depressed level of consciousness ⇒ coma
- early: flapping tremor
- liver fails to clear ammonia ⇒ alteration of synaptic transmission + metabolic alteration in astrocytes
87
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
NUTRITIONAL DISEASES
VITAMIN B12 DEFICIENCY:
- ascending + descending fibers of spinal cord
- numbness in legs ⇒ spastic weakness ⇒ paraplegia
88
119. Primary diseases of myelin. Acquired metabolic and toxic disturbances of the brain:
TOXIC DISORDERS
1. Metals (lead)
2. Arsenic and mercury
3. Industrial chemicals (organophosphates)
4. Methanol ⇒ blindness
5. Environmental pollutants (CO)
6. Ethanol
⇒ excessive intake: brain swelling + death
⇒ chronic: cerebellar dysfunction (trunkal ataxia, unsteady gait, nystagmus)
7. Chemotherapeutic agents
8. Ionizing radiation
⇒ headache, nausea, vomiting, papilledema
⇒ coagulative necrosis in white matter
89
120. Tumors of central and peripheral nervous system:
| CHARACTERISTICS OF CNS TUMORS
```
HISTOLOGY:
- distinction between benign and malignant more subtle
PATTERN OF GROWTH:
- of low grade lesions may still infiltrate ⇒ serious clinical defects
CLINICAL COURSE DEPENDENT ON SITE:
- benign tumor can compress medulla
METASTATIC PROPERTIES:
- rarely metastasize outside CNS
- subarachnoid space provide pathway
```
90
120. Tumors of central and peripheral nervous system:
| CLASSIFICATION OF CNS TUMORS
1. GLIOMAS
- astrocytoma
- oligodendroglioma
- ependyoma
2. NEURONAL TUMORS
- central neurocytoma
- ganglioglioma
- dysembryoplastic neuroepithelial tumor
3. POORLY DIFFERENTIATED TUMORS:
- medulloblastoma
4. MENINGIOMA
5. METASTATIC TUMORS
91
120. Tumors of central and peripheral nervous system:
| FIBRILLARY ASTROCYTOMA
- location: cerebral hemispheres
- symptoms:
* seizures
* headaches
* focal neurologic deficits
- spectrum of histologic differentiation
- types depending on differentiation
* type 1-3: diffuse astrocytoma and anaplastic astrocytoma
* type 4: glioblastoma multiforme
- poor prognosis
- treatment: resection, radiotherapy + chemotherapy (survival of 8-10 months)
92
120. Tumors of central and peripheral nervous system:
| PILOCYTIC ASTROCYTOMA
- benign tumors
- affects children + young adults
- location: cerebellum, 3rd ventricle, optic nerve, cerebral hemispheres
- morphology: cystic appearance, bipolar cells, GFAP positive hairlike projections
93
120. Tumors of central and peripheral nervous system:
| OLIGODENDROGLIOMA
- arise from oligodendrocytes
- loss of heterozygosity for chromosomes 1p and 19q
- age: 40-50s
- symptoms: neurologic complaints, seizures
- location: cerebral hemispheres- white matter
- better prognosis
- treatment: surgery, chemotherapy, radiotherapy
- survival 5-10years
94
120. Tumors of central and peripheral nervous system:
| EPENDYMOMA
- arise next to ependyma-lined ventricular system
- location: 4th ventricle in childhood, spinal cord in adults
- CSF dissemination is common
MORPHOLOGY:
- solid/papillary masses outputting into ventricle
- pseudo-rosettes
95
120. Tumors of central and peripheral nervous system:
| CENTRAL NEUROCYTOMA
- arise from neural tissue
- low-grade tumor
- location: within or adjacent to ventricular system
- characterized by evenly spaced, round and uniform nuclei
96
120. Tumors of central and peripheral nervous system:
| GANGLIOGLIOMA
- arise from neural tissue
- tumors with mixture of glial elements and mature-appearing neurons
- slow growing
- glial component becomes anaplastic ⇒ progress rapidly
- symptoms: seizures
97
120. Tumors of central and peripheral nervous system:
| DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR
- low-grade tumor
- age: childhood
- slow growth + good prognosis after resection
- symptom: seizures
- location: superficial temporal lobe
- morphology: small round cells with features of neurons arranged in columns and around central cores of processes
98
120. Tumors of central and peripheral nervous system:
| MEDULLOBLASTOMA
- age: childhood
- location: cerebellum
- neuronal + glial markers, but undifferentiated
- highly malignant
- poor prognosis without treatment
- radiosensitive
- with total excision 5 years survival - 75%
99
120. Tumors of central and peripheral nervous system:
| MENINGIOMA
- benign tumor in adults
- location: attached to dura or arise from meningothelial cells of arachnoid
- may be found along any external surface of the brain+ in ventricular system ⇒ stromal arachnoid cells of choroid plexus
100
120. Tumors of central and peripheral nervous system:
| SCHWANNOMA
- benign tumors
- arise from Schwann cells
- symptoms due to compression of involved nerve or adjacent structures
- location: cranial vault, cerebellopontine angle, within dura or extradural
- easily surgically removed
101
120. Tumors of central and peripheral nervous system:
| NEUROFIBROMA
1. Cutaneous + solitary neurofibroma
- location: skin, peripheral nerves
- skin tumors: nodules, hyper pigmentation, grow large + pedunculated
2. Plexiform neurofibroma
- involve major nerve trunks
- potential for malignant transformation
102
120. Tumors of central and peripheral nervous system:
| MALIGNANT PERIPHERAL NERVE SHEATH TUMOR
- highly malignant sarcomas
- locally invasive
- multiple recurrence
- metastatic spread
- arise de novo or from transformation of plexiform neurofibroma
- can occur after radiation therapy
103
120. Tumors of central and peripheral nervous system:
| METASTATIC TUMORS
PRIMARY SITES:
- lung
- breast
- skin (melanoma)
- kidney
- GI tract
- form sharply demarcated masses, at grey-white matter junction, surrounded by edema
104
120. Tumors of central and peripheral nervous system:
| METASTATIC TUMORS/ PARANEOPLASTIC SYNDROMES
1. Subacute cerebellar degeneration ⇒ ataxia with destruction of Purkinje cells, gliosis, mild inflammatory infiltrate
2. Limbic enceohalitis ⇒ subacute dementia with perivascular inflammatory cuffs, microglial nodules, neuronal loss, gliosis
3. Subacute sensory neuropathy ⇒ altered pain sensation with loss of sensory neurons of dorsal root ganglia + inflammation
