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Central Nervous System Neurons

Department of Pathology Axonal Reaction


Acute cell injury (Red Neuron)
Atrophy & Neuronal
Degeneration
Intraneuronal Deposits

Glial Cell: Astrocyte


Gray & white matter
Star-shaped, imparted by its
multiple, branching cytoplasmic
processes
(+) GFAP

Astrocytes: Response to Injury


Gliosis
Rosenthal Fibers
Corpora amylacea
Cells Alzheimer Type II Astrocytes
Neurons
Glial Oligodendrocytes
Astrocytes Main cellular component of the
Oligodendrocytes white matter
Ependymal Cells Production & maintenance of
Microglial CNS myelin
Endothelial Cells
Microglia
Neuron Mesoderm-derived cells (bone
marrow)
Irregular/spindly nuclei
CD4+

Microglia: Response to Injury


Proliferation
Developing elongated nuclei (Red
Nuclei)
Forming Aggregates (microglial
nodules)
Neuronophagia

Ependyma
Lines the ventricular system and the
central canal of the spinal cord
Single layer of cuboidal to columnar
cells (variably ciliated)

Common Pathophysiologic
Complications of Brain Pathology

Herniations
Cerebral edema
Hydrocephalus
Cellular Reactions to Injury
Transcarvarial

Herniation Extracranial (Calvarial) Herniation

Shift of the brain through an


extracranial defect
These are generally post
traumatic or post surgical. The
brain can become ischemic and
infarct. Post trauma patients or
patients with significant
intracranial mass effect may
undergo craniectomy to remove
the ipsilateral, overlying bone .
This will allow the brain to
decompress through the defect.
Subfalcine This gross specimen correlates
Expansion of a cerebral with the CT of the brain shifting
hemisphere leading to through the cranial defect
displacement of the cingulate
gyrus Cerebral Edema
Compression of the anterior Vasogenic
cerebral artery Increased vascular permeability
Transtentorial (Uncal or Uncinate) Cytotoxic
Space-occupying lesion in the Altered cell regulation of fluid
temporal lobe or more lateral Interstitial
portion of the cerebral Transudation of fluid from the
hemisphere. ventricular system across the
ependymal lining
Clinical Consequences of Transtentorial
Herniation Morphology: Cerebral Edema
Alteration in consciousness to the Vasogenic Edema
point of coma, secondary to Soft & Swollen brain
compression of the midbrain by the Gyri are flattened, sulci are
impinging uncus widened, ventricles are
Stretching or compression of the compressed
oculomotor nerve (ipsilateral, Widened extracellular space
contralateral or both) between the normally closely
Compression of contralateral cerebral apposed myelinated
peduncle against the free edge of the fibers,distention of endothelial
tentorium cells and pericapillary astrocytic
Aqueductal compression and foot processes and breakdown
hydrocephalus further raising ICP of myelin
Intermittent compression of the post Cytotoxic Edema
cerebral artery Most evident in the gray matter
Duret Hemorrhages Cells are swollen and
vacoulated.
Herniation Interstitial Edema
Tonsillar Herniation (Coning) Abnormal flow of fluid around
One or both cerebellar tonsils the lateral ventricles when there
are displaced into the foramen is an abnormal flow of fluid from
magnum, with compression of the interventricular space.
the medulla and its vital
respiratory center Hydrocephalus
Enlargement of ventricles with an Spinal Dysraphism or Spina
associated increase in volume of CSF Bifida
500 ml/day Myelomeningocoele
140-150 ml (renewed q 6-8 hours) (Meningomyelocoele)
Secreted by the choroid plexus Meningocoele
Types: Forebrain Abnormalities
Non-communicating-blockage Polymicrogyria
anywhere along the ventricular Megalencephaly/ Microcephaly
system Lissencephaly (Agyria)
Communicating obstruction is Neuronal Heterotopias
along the subarachnoid path of Holoprosencephaly
CSF flow, including the sites of Agenesis of the Corpus callusom
its absorption Posterior Fossa Abnormalities
Arnold-Chiari Malformation
(Chiari Type II)
Causes of Hydrocephalus Dandy-Walker Malformation
Syringomyelia & Hydromyelia
Infants and Children
Congenital malformation Neural Tube Defects
Intrauterine or perinatal
infection Etiology: unknown
Vascular diseases Screening:
Neoplasm Maternal Blood Samples for
Adults alpha feto protein
Sudden or gradual obstruction Recurrence rate: 4-5%
of flow Risk factor: Folate Deficiency
Elderly
Normal pressure hydrocephalus Anencephaly
Mental slowness, incontinence, Malformation of the anterior end of the
gait disturbance neural tube, with the absence of brain
& calvarium
Hydrocephalus ex vacou 1-5/ 1000 live births
Cerebral atrophy, extensive tissue More common in females
loss, compensatory expansion of the Develop at 28 days of gestation
ventricular system Area cerebrovasculosa -consists of
scattered primitive neuroglial tissue
Morphology of Hydrocephalus elements within an irregular vascular
Interruption of the ependymal lining proliferation.
with ependymal granulations,
interstitial periventricular edema with Encephalocoele
thinning out of the myelin fibers Defect in the cranium
Diverticulum of malformed CNS tissue
Malformations & Developmental
Occurs in the occipital region or in the
Diseases
posterior fossa
Neural Tube Defects
Spinal Dysraphism or Spina bifida
Forebrain Abnormalities
Two Forms:
Posterior Fossa Abnormalities
Syringomyelia & Hydromyelia Asymptomatic bony defect
(spina bifida occulta)
Neural tube defects A severe malformation with a
Anencephaly flattened disorganized segment
of the spinal cord associated
Encephalocoele
with an overlying meningeal out
pounching
Meningocoele/Myelomenigocoele
Myelomeningocoele
(Meningomyelocoele)
Extension of CNS tissue through
a defect in the vertebral column
Meningocoele
Meningeal extrusion Neuronal Heterotopias
Stranded clusters of neurons
Strewn along the path of migration

Holoprosencephaly
Incomplete separation of cerebral
hemispheres across the midline
Forebrain abnormalities Midline facial abnormalities including
cyclopias
Polymicrogyria Arrhincephaly
Loss of the normal external contour of Trisomy 13 and Trisomy 18
the convolutions
Small, unusually numerous , irregularly
formed convolutions
Gray matter few layers, with
entraptment of apparent meningeal Holoprosencephaly
tissue at points of fusion
Localized tissue injury during the time
of neuronal migration.

Megalencephaly/Microcephaly
Microcephaly
Abnormally small brain
Chromosomal abnormalities,
fetal alcohol syndrome, HIV
infection in utero
Reduced neurons
Macrocephaly Agenesis of the Corpus Callosum
Lissencephaly (Agyria) Absence of white matter bundles that
Decreased to total absence of carry cortical projections from one
gyri hemisphere to the other.
Smooth brain X-ray: Mishapped lateral ventricles
(bat-wing deformity)
Lissencephaly (Agyria) Lipoma may occupy the defect

Posterior Fossa Abnormalities

Posterior Fossa Abnormalitites: Arnold-


Chiari Malformation
Chiari Type II malformation
Small posterior fossa, malformed Perinatal Injury
midline cerebellum with extension of
the vermis through the foramen Perinatal Brain Injury
magnum Cerebral Palsy non progressive
Hydrocephalus & Lumbar neurologic motor deficit with onset
myelomeningocoele during the perinatal period, regardless
of etiology
Intraparenchymal Hemorrhage within
the germinal matrix, near the junction
of thalamus and caudate nucleus
Periventricular leukomalacia (PVL)
chalky white plaques consists of
discrete regions of white matter
necrosis and mineralization
Perinatal Ischemic Lesion
Gliotic gyri (ulegyria)
Status marmoratus

Intraventricular Hemorrhage (IVH)


Dandy-Walker Malformation
Enlarged porterior fossa
Absent cerebellar vermis or
rudimentary form
Large midline cyst

Syringomyelia/Hydromyelia
Hydromyelia
Segmental or continous
Periventricular leukomalacia
expansion of the ependymal-
Shock lesions
lined central canal of the cord
Syringomyelia
Trauma
Formation of cleft-like cavity in
the inner portion of the cord Skull Fractures
Syringobulbia Diastatic
Slit-like cavity extend into the Displaced skull fractures
brainstem
Concussion
Signs & Symptoms: Syrinx Clinical syndrome brought about by
Syrinx cavities associated with
closed head injury
intraspinal tumors, degenerative Reversible and unassociated with
diseases.
permanent structural damage
Sensory loss of pain and temperature
Transient neurologic dysfunction, loss
in the upper extremeties, retention of
of consciousness, respiratory arrest &
the position sense, and absence of
loss of reflexes
motor deficits, due to early
Neurologic recovery: complete
involvement of the crossing anterior
Amnesia: persist
spinal commisural fibers
Direct Parenchymal Injury
Contusion
Transmission of kinetic energy
to the brain
Laceration
Penetration of an object and
tearing of tissue
Coup injury injury at the
point of impact
Contrecoup injury
damage to the brain
opposite the point of
impact White Matter Injury
Axonal retraction balls
Contussion Demostrated by silver staining
Contrecoup lesion in the frontal and Angular acceleration without impact
temporal poles are (arrows) are Axonal swelling
located opposite to a small coup lesion Decreased number of microglia
over the cerebellum Degeneration of fiber tracts

Laceration Epidural Hematoma


Tissue loss Middle meningeal injury
Temporal area
Histologic Morphology: Contusion Lucid for several hours before
24 hours- evidence of neuronal injury neurologic deficits
24-48 hours axonal swelling, Expand rapidly: Neurological
infiltrates emergency
Plaque jaune
Depress, retracted,yellowish- Subdural Hematoma
brown patches involving the Bridging veins
crests of gyri most commonly Manifest within the 1st 48 hours of
located at the sites of contre- injury
coup lesions Nonlocalizing sign, slowly progressive
neurologic deterioration
Course of Organization:
Lysis of clot
Fibroblast
Plaque jaune
Granulation tissue
Complication: Rebleeding

Other Traumatic Injury to the Brain


Traumatic subarachnoid hemorrhage
with intraparenchymal damage
Spinal cord Injury
Cerebrovascular Diseases

Hypoxia, Ischemia & Infarction


Intracranial Hemorrhage
Hypertensive Cerebrovascular Disease

Cerebrovascular Diseases
Third leading cause of death (after
heart disease and cancer).
Three categories:
Thrombosis Interruption of the normal
Embolism circulatory flow
Hemorrhage
Two processes: Acute Ischemic Injury
Hypoxia, ischemia and Ischemic (Hypoxic) Encephalopathy
infarction Generalized reduction of
Hemorrhage cerebral perfusion with
widespread damage
Cerebral Infarction
Focal ischemic necrosis that
follows reduction or cessation of
blood flow to the localized area
of the brain

Ischemic (Hypoxic) Encephalopathy


Mild: transient postischemic
confusional state with eventual
recovery
Global: widespread brain necrosis
Focal: localized area
Brain Death
Diffuse cortical Injury flat EEG
Brain Stem Damage
Absent reflexes
Respiratory drive
Respirator Brain
Soft, puree- like tissue that does
not fix and take stain well
Morphology of Hypoxic Brain
Swollen (Widened gyri,
narrowed sulci)
Poor demarcation of gray &
white matter
12-24 hours
Hypoxia, Ischemia & Infarction Acute neuronal cell
15% of the resting cardiac output change (red
20% of the total body oxygen neuron)-
consumption microvascularizatio
Normal cerebral function: 8-10 n, eosinophilia,
seconds after cerebral ischemia nuclear pyknosis &
Irreversible brain damage: 6-8 minutes karyorrhexis
30-60 minutes after reduction of blood 24 hours to 2 weeks
sugar to zero Necrosis of tissue,
influx of
macrophages,
Mechanism of O2 deprivation vascular
proliferation,
Functional Hypoxia reactive gliosis
>2 weeks
Low inspired partial pressure of
O2 Repair
Impaired O2 carrying capacity
Sensitivity of Cells to injury
Inhibition of O2 use by tissue
Neurons most sensitive
Ischemia (Transient or Permanent)
Astrocytes
Olgodendrocytes 2-10 days
Gelatinous and friable
Respirator Brain 10 days 3 weeks
Tissue liquefies and eventually
removed leaving a fluid-filled
cavity
12 hours
Ischemic neuronal damage and
edema
Loss of the usual tinctorial
characteristics of white & gray
matter structures
Swelling of endothelial & glial
cells, mainly astrocytes
Ischemic (Hypoxic) Encephalopathy
Disintegration of myelinated
Watershed or Border Zone Infarcts
fibers
Wedge-shape areas of 48 hours
coagulation necrosis that occur
Phagocytic cells, adventitial
in those region of the brain and
histiocytes and activated
spinal cord that lie distal to the
microglial
arterial irrigation.
Months
Cerebral Infarction Nuclear and cytoplasmic
Stroke enlargement subsides
Clinical term that refers to the
Non Traumatic Intracranial Hemorrhage
sudden development of a
neurologic deficit caused by
Intraparenchymal Hemorrhage
abnormality of the blood supply
Thrombosis or Embolism 80% arterial hypertension
Thrombosis Intracerebral arteriovenous
extracerebral carotid malformations
system Tumor
Atherosclerosis Hemorrhagic diathesis
Arteritis Tb & Amyloid angiopathy
Syphilis
Embolus intracranial Hypertensive Intracerebral Hemorrhage
vessels Putamen 50-60%
Shower embolization (fat embolism) Thalamus
generalized cerebral dysfunction Pontine tegmentum
Spinal cord infarction - Hypoperfusion Cerebellar hemispheres
Hemorrhagic (Red) Infarct Ganglionic hemorrhages
Multiple, confluent, petechial Complication: Charcot Bourchard
hemorrhages typically Aneurysm
associated with embolic events Extravasation of blood with
Reperfusion compression of the adjacent
Anticoagulation is parenchyma
contraindicated
White (Pale, Bland) Infarct Subarachnoid Hemorrhage (SAH)
Associated with thrombosis Rupture of berry aneurysm
6 hours of irreversible injury Extension from a traumatic hematoma
48 hours Rupture hypertensive intracerebral
Pale, soft, and swollen, and the hemorrhage into the ventricular
system
corticomedullary junction
Vascular malformation
becomes distinct
Hematologic disorder
Tumor collagenized walls, devoid of nervous
tissue
Berry Aneurysm Cerebellum, pons and subcortical
Saccular or congenital aneurysm regions
Other uncommon aneurysms:
Atherosclerotic (fusiform) Hypertensive Cerebrovascular Disease
Mycotic or traumatic aneurysm Acute Hypertensive Encephalopathy
Dissecting aneurysm Clinicopathologic syndrome
Pathogenesis: Unknown arising in the hypertensive
Age & Hypertension patient characterized by
Collagen disorders evidence of diffuse cerebral
74% of patient: Rupture dysfunction
5th decade Headaches, confusion, vomiting,
convulsions, coma
Females
Cause of Death: Cerebral
20-30% multiple
edema with Herniation
Headache
Healing Phase: meningeal fibrosis and Binswanger Disease
scarring, causing obstruction of CSF Pattern of injury is in the subcortical
flow white matter with axonal & myelin loss
Thin walled outpouchings of the artery
Few mm to 2-3 cm Lacunar Infarcts
Bright red,shiny surface and a thin Lake like spaces 15 mm wide
translucent wall Non cortical area of the brain
Rupture occurs in the apex of the sac
Slit Hemorrhages
Due to rupture of small caliber blood
vessels
Hemorrhage ---------slit like spaces
Focal tissue destruction, pigment
laden macrophages and gliosis

Infections

Route of Entry
Hematogenous
Direct Implantation
Vascular Malformations Local Extension
Arteriovenous malformations (AVMs) PNS rabies & herpes simplex
Most important
Abnormally tortous, Meningitis
misshapen vessels
Males affected 2x than Etiology
females Infants: E.coli & Group B strep
10-30 y.o Infants & Children: H. influenzae
Seizure, intracerebral Adolescents & young adults:
and/or subarachnoid Neisseria meningitidis
bleed Elderly: Streptococcus
Cavernous angiomas pneumoniae & Listeria
Capillary telangiectasia monocytogenes
SSx of menigeal irritation:
Cavernous Hemangioma headache, photophobia,
Greatly distended, loosely organized irritability, clouding of
vascular channels with thin consciousness, neck stiffness
Mental confusion
Bacterial Meningitis Vomiting
Complications:
Arachnoid fibrosis
hydrocephalus
Obliterative endarteritis
Arterial occusion - infarction
CSF
Pleocytosis
Elevated protein
Sugar : Normal or reduced

N. meningitidis

Neurosyphilis
Tertiary stage of syphilis
Impaired cell mediated
immunity
Patterns of CNS involvement:
Meningovascular syphilis
Heubner arteritis
Paretic neurosyphilis
Widespread individual
Viral Meningitis cell death and
Nonbacterial or aseptic consequently brain
Lymphocytic pleocytosis, moderate atrophy
protein elevation, normal protein Progrssive loss of mental
Enterovirus (echovirus, coxsackie, functions, mood
polio) alteration (delusion of
Brain swelling grandeur) and
Lymphocytic Infiltrates in the terminating in severe
leptomeninges dementia
Argyll Robertson pupil
Brain Abscess Loss of cortical neurons
Direct implantation of the organism, with proliferation of
local extension from adjacent foci microglia and gliosis
(mastoiditis) or hematogenous General paresis of the
Predisposing factors: insane
Acute bacterial endocarditis Tabes Dorsalis
Cyanotic heart disease Damage to the sensory
Chronic pulmonary sepsis nerve in the dorsal roots
Impaired position sense
Tuberculosis and ataxia (locomotor
Gelatinous or fibrinous exudates often ataxia)
at the base of the brain Loss of pain sensation
Granuloma formation (Charcot joints)
Meningoencephalitis
Signs & Symptoms: Viral Meningoencephalitis
Headache
Malaise
Spongiform Encephalopathies: Post polio syndrome: 25-35 years after
Creutzfeldt-Jacob Dse & Kuru resolution of the initial illness

Spongiform change in the gray matter Rabies


Prion Cebrebral edema
Abnormal form of a normal IP: 1-3 months
cellular protein and is relatively Hippocampal neurons and the
resistant to digestion by cerebellar Purkinje cells are the places
proteinase K Negri bodies are most likely to appear.
Severe neuronal loss
Reactive astrocytosis Fungal Infections
Kuru plaques 3 basic patterns
Chronic meningitis
Herpes Simplex Virus Vasculitis
Parenchymal invasion

Aspergillus

CMV
Fetus and immunosuppresed
individuals Toxoplasmosis
Periventricular necrosis
Severe brain destruction -
microcephaly and
periventricular calcification

Cytomegalovirus

Cysticercosis

Poliomyelitis
Picornavirus group
ofenterobacteriaciae Demyelinating Disease
Anterior motor neuron of the spinal Multiple Sclerosis
cord Dysmyelinating Diseas (Leukodystrophies)
Meningeal irritation Myelinolytic Diseases (Spongy
CSF: Aseptic meningitis Myelinopathies)
Demyelinating Diseases Globoid cell leukodystrophy (Krabbes
Acquired conditions characterized by Disease)
preferential damage to myelin with Beta-galactocerebrosidase
preservation of the axons Onset:
Causes: 6 months old
Auto-immune SSx:
Infection rigidity, decreased alertness,
fatal (2 y.o.)
Multiple Sclerosis Brain:
20-40 y.o. Demyelination & globoid bodies
Female (multinucleated histiocytes
Chronic remitting or chronic around the blood vessels)
progressive
Oligoclonal bands in CSF containing Krabbe Disease
excessive protein (IgG and Myelin
Basic Protein)
Etiology: autoimmune
(?) viral

Relapsing episodes of paresthesia,


visual disturbance (optic nerve) and
incoordination.
Metachromatic Leukodystrophy
Dysmyelinating Disease
(Leukodystrophies)

Adrenoleukodystrophy (ALD)
X- linked
Young boys
Adrenal (glucocorticoid) failure:
Accumulation of long chain fatty acids
Pronounced lymphocytic infiltrates
Large plaques of demyelination and
dies within 3 years
Adult forms: Slowly developing spastic
paralysis, cerebellar ataxia, peripheral
neuropathy.
Leukodystrophies
Krabbe Disease
Metachromatic Leukodystrophy (MLD)
Classic Metachromatic
Late infantile presentation lack of encepathalomyopathies
Adrenoleukodystrophy
arylsulfatase A
Systemic especially gallbladder, Pelizaeus-Merzbacher Disease
kidney & neuronal lipidosis Canavan Disease
Granulovacoular degeneration
Mitochondrial Encephalomyopathies Hirano bodies
Leigh Syndrome
Myoclonic epilepsy and ragged red Picks Disease
fibers Peak incidence at 60 y.o.
Mitochondrial encephalomyopathy, Male = female
lactic acidosis and stroke-like episodes AD
Kearns-Sayre Syndrome Profound dementia
Sharply demarcated focal (lobar)
Leigh Syndrome subacute necrotizing atrophy
encephalopathy Pick bodies: subtle, swollen,
filamentous, eosinophilic bodies in the
cytoplasm of the neurons

Degenerative Disease of Basal Ganglia


& Brain Stem
Parkinsonism
Clinical syndrome characterized
by: diminished facial expression,
stooped posture, slowness of
voluntary movement,
festinating gait, rigidity & pill
rolling tumor
Damage to the nigrostriatal
dopaminergic system
Degenerative Disease
Parkinsons Disease
Alzheimers Disease
Picks Disease

Degenerative diseases
Diseases of the gray matter
characterized by progressive loss of
neurons with associated changes of
the white matter tracts Huntingtons Disease
Hallmark in diagnosis: presence of AD
protein aggregates that are resistant 35-40 y.o.
to degeneration
Chorea, psychiatric changes
Dementia
(promiscousness, violence, sociopathic
behaviour, depression) later confusion,
Alzheimers Disease
memory deficit and dementia.
Most common cause of dementia in
Marked atrophy of the caudate nuclei
elderly
& putamen
Marked atrophy (frontal lobes)
Cell loss, senile plaques, neurofibrillary Spinocerebellar Degeneration
tangles, granulovacoular
degeneration, amyloid angiopathy Degenerative Diseases affecting the
Hirano bodies eosinophilic football Motor Neurons
shaped structures Amyotrophic Lateral Sclerosis
Cerebral amyloid angiopathy Bulbospinal Atropy
Dehydration
Amyotrophic Lateral Sclerosis Hepatic encephalopathy
Bunina Bodies Alzheimer Type II astrocytosis
PAS positive cytoplasmic
inclusions that appear to be a Toxic Disorders
remnant of autophagic vacoules Carbon monoxide
Methanol
Genetic Metabolic Diseases Degeneration of the retinal
Neuronal Storage Disease ganglion cells
Leukodystrophies Formate
Mitochondrial encephalopathies Ethanol
Cerebellar atropy and loss of
Toxic & Acquired Metabolic Diseases granule cells predominantly of
Vitamin Deficiencies the anterior vermis
Thiamine (Vitamin B1) Bergmann gliosis
Beri-beri Radiation
Wernicke encephalopathy Combine Methotrexate and Radiation-
benign, abrupt Induced Injury
Hemorrhage &
necrosis in the
mamillary bodies
Psychotic
symptoms
Ophthalmoplegia
Korsakoff syndrome
memory disturbance and
confabulation
Vitamin B12
Slight ataxia, spastic
weakness of the lower
extremeties
Swelling of the myelin
layers
Degeneration of the
axons of both ascending
tracts of the posterior
columns and descending
pyramidal tracts

Wernicke encephalopathy
Periventricular hemorrhages
and discoloration of mamillary
bodies.
Fibrillary gliosis

Neurologic Sequelae of Metabolic


Disturbance
Hypoglycemia
Hippocampus & Purkinje fibers
of the cerebellum
Hyperglycemia
Ketoacidosis & hyperosmolar
coma