Transcript The Central Nervous Systemx

Cellular Responses to Injury
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Reactions of neurons to injury
 Acute neuronal injury – “red neurons”
 Subacute and chronic neuronal injury –
degeneration
 Axonal reaction – regeneration
 Neuronal inclusions
Cellular Responses to Injury
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Reaction of astrocytes to injury
 Metabolic buffers and detoxifiers
 Gliosis
 Gemistoytic astrocytes
 Alzheimer type II astrocytes
 Rosenthal fibers
 Alexander disease
 Lafora bodies
Cellular Responses to Injury
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Other glial cells – oligodendrocytes and
ependyma
 More limited repertoire of reactions
 Inclusions
 CMV – extensive ependymal injury
Cellular Responses in Injury
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Reactions of microglia to injury
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Fixed macrophages in the CNS
Proliferation
Development of elongated nuclei
Formation of aggregates about small foci of
tissue necrosis ( microglial nodules)
 Congregation around cell bodies of dying
neurons ( neuronophagia)
 Blood-derived macrophages are principal
phagocytic cells in inflammatory foci
Cerebral Edema, Hydrocephalus,
and Raised Intracranial Pressure
and Herniation
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Cerebral Edema
 Vasogenic edema
 Cytotoxic edema
 Hydrocephalic edema
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Hydrocephalus
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Accumulation of excessive CSF within the ventricular system
Communicating
Noncommunicating
Hydrocephalus ex vacuo
Raised Intracranial pressure and herniation
 Subfalcine ( cingulate) herniation
 Transtentorial ( uncinate,mesial temporal) herniation
 Tonsillar herniation
Malformations and
Developmental Diseases
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Neural tube defects
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Encephalocele
Spinal dysraphism ( spina bifida)
Myelomeningocele
Meningocele
Anencephaly
Folic acid, alpha-fetoprotein
Forebrain anomalies
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Megaloencephaly or microencephaly
Lissencephaly ( agryia)
Polymicrogyria
Neuronal heterotopias
Holoproencephaly
Agensis of the corpus callosum
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Posterior fossa anomalies
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Dandy-Walker malformation
Arnold-Chiari malformation ( Chiari type II),
Chiari I malformation
Syringomyelia and hydromyelia
Perinatal Brain Injury
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Brain injury occurring in the perinatal
period is an important cause of childhood
neurologic disability
Cerebral palsy
Intraparenchylmal hemorrhage within the
germinal matrix
Periventricular leukomalacia
Multicystic encephalopathy
Ulegyria
Status marmoratus
Trauma
Skull fractures
 Parenchymal Injuries
 Traumatic Vascular Injury
 Sequelae of brain tumors
 Spinal cord Trauma – level of lesion
determines extent of neurologic
manifestation
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Trauma
Anatomic location and limited capacity
for functional repair – major
determinants of consequences of
trauma
 Skull fractures, parenchymal injury,
vascular injury or combination
 Penetrating or blunt (open or closed)
injury
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Trauma
Displaced skull fracture
 Basal skull fracture – CSF leak
 Diastatic
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Trauma
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Parenchymal Injuries
 Concussion – clinical syndrome of altered
consciousness secondary to head injury
typically brought about by a chance in the
momentum of the head
○ Instantaneous LOC, temporary respiratory
arrest, loss of reflexes, amnesia for the event,
post-concussive neuropsychiatric syndromes
Trauma
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Direct parenchymal injury
 Contusion
 Laceration
 Coup and contrecoup
 Plaque jaune
 Diffuse axonal injury
Trauma
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Traumatic vascular injury
 Epidural hematoma – middle meningeal
artery, temporal skull fractures, lucid interval
 Subdural hematoma – bridging veins, infants
and elderly, lysis -> growth of fibroblasts into
the hematoma -> early development of
hyalinized CT, chronic subdural – multiple
episodes of repeat bleding
Trauma
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Sequelae of brain trauma
 Post-traumatic hydrocephalus
 Post-traumatic dementia
 Punch-drunk syndrome
 Post-traumatic epilepsy
 Meningiomas
 Infectious diseases
 Psychiatric disorders
Cerebrovascular Diseases
Hypoxia, Ischemia, and Infarction
 Hypertensive cerebrovascular disease
 Intracranial hemorrhage
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Cerebrovascular Diseases
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Hypoxia, ischemia, and infarction
 Global cerebral ischemia
○ Hypotension, hypoperfusion, low-flow states
○ Hierarchy of sensitivity to insult
○ Selective vulnerability
○ Border zone “watershed” infarcts
 Focal cerebral ischemia
○ Adequacy of collateral flow
○ Majority of thrombotic occlusions are due to
atherosclerosis
○ Emboli – mural thrombi, MI valvular disease,
paradoxical
○ Vasculitis
Hypertensive Cerebrovascular
Disease
Lacunar infarcts
 Slit hemorrhages
 Hypertensive encephalopathy
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 Diffuse cerebral dysfunction
 Headaches, confusion, vomiting, convulsions,
coma
 Increased intracranial pressure
 Vascular dementia – Multi-infarct, dementia, gait
abnormalities, pseudobulbar signs,
superimposed focal defects, Binswanger
disease – loss of large areas of white matter
Intracranial Hemorrhage
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Intracerebral (intraparenchymal)
 Hypertension is the most common
underlying cause of primary brain
parenchymal hemorrhage
 Cerebral amyloid angiopathy
 Cerebral autosomal dominant arteriopathy
with subcortical infarcts and
leukoencephalopathy
Intracranial Hemorrhage
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Subarachnoid hemorrhage
 Saccular (berry) aneurysm – most frequent
cause, Table 28-19 – common sites,
sporadic most common, also AD polycystic
kidney disease, Ehlers-Danlos, type IV, NF
type 1, Marfan), “Worst headache of my life”
Intracranial Hemorrhage
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Vascular malformations
 Arteriovenous malformation
 Cavernous malformation
 Capillary telangiectasias
 Venous angiomas
Infections
Acute meningitis
 Acute focal suppurative infections
 Chronic bacterial meningoencephalitis
 Viral meningoencephalitis
 Fungal Meningoencephalitis
 Other infectious diseases of the nervous
system
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Principal routes of spread of
microorganisms into the CNS
Hematogenous spread
Direct implantation
Local extension
Transport along the peripheral NS
Meningitis
Inflammatory process of the leptomeninges
and CSF within the subarachnoid space
Acute pyogenic (bacterial)
Purulent CSF, exudate within the
leptomeninges, pus tracts along blood
vessels
Aseptic (viral)
less fulminant
Chronic (TB, syphilis, cryptococcal, lyme
disease
Acute Focal Suppurative
Infections
 Brain abscess
○ Acute bacterial endocarditis, congenital heart
disease, chronic pulmonary sepsis,
immunosuppression
 Subdural empyema
 Extradural abscess
Viral Meningoencephalitis
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Arthropod-borne – West Nile
Herpes simplex type 1 and type 2
Herpes Zoster
CMV
Poliomyelitis – anterior horn cells
Rabies – Negri bodies
HIV
Progressive multifocal leukoencephalopathy –
JC polyomavirus
Subacute sclerosing panencephalitis measles
Fungal Meningoencephalitis
Candida, Mucor, Aspergillus,
Crytococcus
 Chronic meningitis
 Vasculitits
 Parenchymal invasion
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Protozoal
Cerebral amebiasis fatal necrotizing
encephalitis or chronic
 Toxoplasmosis
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 Opportunistic
 Immunosuppression or maternal infection
 Multiple ring-enhancing lesions
Transmissible Spongiform
Encephalopathies (Prion
diseases)
Creutzfeldt-Jacob disease
 Gerstmann-Straussler-Scheinker
syndrome
 Fatal familial insomnia
 Kuru
 Figure 28-31
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Demyelinating Diseases
Multiple sclerosis
 Neuromyelitis optica – Devic disease
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 Bilateral optic neuritis and spinal cord
demyelination
Acute disseminated encephalomyelitis
and acute necrotizing hemorrhagic
encephalomyelitis
 Other diseases with demyelination
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 Central pontine myelinolysis – rapid
correction of hypomatremia
Multiple Sclerosis
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Autoimmune demyelinating disorder
characterized by distinct episodes of
neurologic deficits, separated in time,
attributable to white matter lesions that are
separated in space
Immune response against components of the
myelin sheat
Plaques – active, inactive, shadow
Visual impairment, cranial nerve signs, ataxia,
nystagmus, spinal cord lesions,
CSF – elevated protein, 1/3 pleocytosis,
increased IgG
Degenerative Diseases
Degenerative diseases affecting the
cerebral cortex
 Degenerative diseases of basal ganglia
and brainstem
 Spinocerebellar degenerations
 Degenerative diseases affecting the
motor neuron
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Degenerative Diseases affecting
the Cerebral cortex
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Alzheimer disease
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Frontotemporal dementias
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Most common cause of dementia in the elderly
Most cases are sporadic, 10% familial
Cortical arophy
Neuritic plaques
Neurofibrillary tangles
Abeta peptides
Abnormal forms of protein tau
Neuropil threads
CAA
Frontotemproal dementia with parkinsonisn linked to Tau mutations
Pick disease
Progressive supranuclear palsy
Corticobasal degneration
Frontotemporal dementias withou tau pathology
Vascular dementia
Degenerative Diseases of Basal
Ganglia and Brainstem
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Parkinsonism – diminished facial expression,
stooped posture, slowness of voluntary movements,
festinating gait, rigidity, “pill-rolling” tremor
Parkinson disease – dopamine, pallor of substantia
nigra, alpha-synuclein mutations, lewy bodies
Dementia with Lewy bodies
Multiple system atrophy – inclusions in
oligodendrocytes
Huntington disease – progressive movement
disorders, dementia, degeneration of striatal
nuerons, atrophy of caudate nucleus,
Spinocerebellar Degeneraitons
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Spinocerebellar ataxia
 Friedreich ataxia – frataxin mutations, GAA
trinucleotide-repeat, cardiomyopathy
 Ataxia-telangiectasia - immunodeficeincy
Degenerative diseases affecting
Motor Neurons
Amyotrophic lateral sclerosis – lower
motor and upper motor neurons
 Bulbospinal atrophy ( Kennedy
syndrome)
 Spinal muscle atrophy
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Genetic Metabolic Diseases
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Neuronal Storage diseases
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Leukodystrophies
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Neuronal ceroid lipofuscinoses
Tay-Sachs disease
Krabbe disease - deficiency of galatocerebroside beta-galactosidase
Metachromic leukodystrophy – deficiency of lysosomal enzyme arylsulfatase
Adrenoleukosystrophy
Pelizaeus-Merzbacher disease
Canavan disease
Alexander disease
Vanisning-white-matter leukodystrophy
Mitochondrial encephalomyopathies
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Mitochondrial encephalopathy, lactic acidosis, strokelike episodes (MELAS)
Myoclonic epilepsy and ragged red fibers (MERRF)
Leigh syndorme (subacute necrotizing encephalopathy
Kearn-Sayre syndrome
Alpers disease
Toxic and Acquired Metabolic
Diseases
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Vitamin deficiencies
 Vitamin B12
 Thiamine (B1)
○ Beriberi, Wenicke encephalopathy and Korsakoff syndrome
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Neurologic sequelae of metabolic disturbances
 Hypoglycemia
 Hyperglycemia
 Hepatic encephalopathy
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Toxic disorders
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Carbon monoxide
Methanol
Ethanol
Radiation
Combined radiation and methotrexate induced injury
Tumors
Gliomas
 Neuronal tumors
 Poorly differentiated neoplasms
 Other parenchymal tumors
 Meningiomas
 Paraneoplastic syndromes
 Peripheral nerve sheath tumors
 Familial tumor syndromes
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Tumors
20% of all childhood cancers are CNS
tumors
70% of childhood tumors arise in the
posterior fossa
70% of adult tumors arise in cerebral
hemispheres, supratentorial
Rarely metastasize outside of the CNS
Symptoms – seizures, headaches, focal
neurological deficits, hydrocephalus,
ataxia
Gliomas
Astrocytomas
Infiltrating vs non-infiltrating (pilocytic)
Grade I – pilocytic – often cystic
Grade II – diffuse astrocytoma
Grade III – anaplastic astrocytoma
Grade IV – glioblastoma (pseudopalisading)
Oligodendrogliomas
White matter
Well-circumscribed, better prognosis
Ependymomas
NF2, ependyma-lined ventricular system
Perivascular pseudorosettes
Subepndymomas
Choroid plexus papillomas/ carcinomas
Colloid Cyst of third ventricle
Medulloblastoma
Poorly differentiated
Well-circumscribed
Midline of the cerebellum
Desmoplastic variant
Drop metastases – cauda equina
Meningiomas
Attached to the dura
Usually benign
En plaque
Psammoma bodies
Atypical
Anaplastic
Metastatic
¼ to ½ of intra-cranial tumors in
hospitalized patients
Five most common
Lung
Breast
Melanoma
Kidney
GI
Peripheral Nerve Sheath Tumors
Schwannoma
Neural crest-derived Schwann cell
Acoustic neuroma – actually vestibular
Neurofibroma
Cutaneous
Peripheral nerve – solitary or plexiform
Malignant peripheral sheath tumors
Familial Tumor Syndromes
Neurofibromatosis Type I – AD, Lisch nodules, café au lait spots
Neurofibromatosis Type II – AD, 8th nerve schannomas and
multiple meningiomas
Tuberous Sclerosis – AD, hamartomas ( cortical tubers) and
benign neoplasms of the brain; seizures; liver, kidney,
pancreas cysts; angifibromas, shagreen patches, ash-leaf
spots, subungal fibromas
Von Hippel – Lindau Disease – AD, hemangioblastomas
(cerebellum and retina); cysts of liver, pancreas, kidney;
renal cell carcinoma, pheochromocytomas