Pathology of the Central Nervous System Flashcards
Nervous system is largely comprised of
Permanent cells (neurons) and stable cells (glia)
Do the CNS have an ability for. exansion
CNS exists within a physically unyielding and restrictive environment (the skull and spinal canal) with little ability for expansion
- Increased intracranial pressure is an event common to many pathological conditions
Human brain damage
Human brain exhibits remarkable regional specialization of function; clinical loss of function may result from damage to extremely small and specific regions
- Many diseases are the result of dysfunction at the level of receptors and transmitters, without apparent morphological changes
Blood-Brain-Barrier
Physico-chemical system regulating movement of nutrient and chemical into and out of the CNS
- BBB includes transporter that prevent surges of nutrients/AAs and neurotransmitter
- Primary BBB resides at the level endothelial cells, joined by tight junction to prevent promiscuous entry
- Astrocytes provide secondary BBB, fluid volume control
Where do BBB resides at?
The level of endothelial cells, joined
by tight junctions to prevent promiscuous entry
What provides secondary BBB
Astrocytes; fluid volume control
Cerebral Spinal Fluid
Transudate of blood formed by specialized cells (choroid plexus) within ventricles
- 600mL of CSF formed daily. 125-150mL in ventricles at any one time
- CSF replaced multiple times at each day
- CSF contains 0-6 WBCs/mL, 50-75mg/dL glucose (60% of serum glucose levels)
- CSF pressure is 80-180 mm water (5-14 mmHg) recumbent
CSF may be sampled
by Lumbar puncture
Where is transudate of blood formed
by specialized cells (choroid plexus) within ventricles
What do each part of the brain
Frontal Lobe
Parietal Lobe
Occipital Lobe
Temporal Lobe
Cerebellum
Brain Stem
Screen Shot
Frontal Lobe
- Problem solving
- Speaking
- Emotional traits
- Reasoning
- Voluntary motor activity
Brain Stem
- Breathing
- Temp
- Digestion
- Sleep/Alertness
- Swallowing
Cerebellum
- Balance
- Coordination and control of voluntary movement
- Fine muscle control
Temporal Lobe
- Understanding language
- Behavior
- Memory
- Hearing
Occipital Lobe
- Vision
- Color perception
Parietal Lobe
- Knowing right from left
- Sensation
- Reading
- Body orientation
Somatic Sensory Nuclei
Gets information by afferent sensory information
Somatic motor nuclei
Sends efferent signals to muscle and glands via the ventral root
Pattern of Pyramidal Motor Neuron Injury
- Upper motor neuron injury (‘brain injury’)
- Lower motor neuron injury (‘cord injury’)
Upper motor neuron injury (‘brain injury’)
- Primarily contralateral involvement
- Spastic paralysis, contractures
- Muscle is hypertonic
- Minimal atrophy
Lower motor neuron injury (‘cord injury’)
- Flaccid paralysis
- Prominent atrophy
- Contractures
Extrapyramidal Motor System
Function to fine tune and adjust action of the pyramidal system to enhance their precision and maintain muscle tone and posture
- Control automatic voluntary movements (eg. walking, riding a bicycle); inhibits involuntary movements
- Actions are involuntary and capable of great speed and precision
Input arises from deep brain nuclei, including the striate ganglia, substantia nigra, red nucleus
- Acts on ipsi and contralateral motor functions
- Damage causes increased muscle tone and rigidity or chorea (sudden involuntary movements)
Where do the extrapyramidal motor system input arises from?
Input arises from deep brain nuclei, including the striate ganglia, substantia nigra, red nucleus
What do Extrapyramidal Motor System do?
Functions to ‘fine-tune and adjust’ actions of the pyramidal system to enhance their precision, and maintains muscle tone and posture
- Controls automatic voluntary movements (eg. walking, riding a bicycle); inhibits involuntary movements
Cerebellar Dysfunctions
Ataxia:
- Disturbance of posture and gait which doens’t get worse when patient closes his/her eyes
- Patient will swerve or fall to injured side
- Decompensation of movement
- Dysmetria: inability to stop movement (past-pointing)
- adiadochokinesia
- scanning speech
Tremor
- Intention tremor that is absent at rest
Fine Touch Proprioception Vibration
(Primary Sensory) neuron synapses in the medulla ==> (Secondary sensory) neuron crosses midline of body in medulla ==> (Synapse with) tertiary sensory neuron in the THALAMUS ==> (Tertiary sensory) neuron terminates in somatosensory cortex
Irritants, Temperature, Coarse Touch
(Primary Sensory) neuron synapses in dorsal horn of spinal cord ==> (Secondary sensory) neuron crosses midline of body in spinal cord ==> (Synapse with) tertiary sensory neuron in the THALAMUS ==> (Tertiary sensory) neuron terminates in somatosensory cortex
Sensory and Proprioceptive Functions
Loss of it will cause
- Inability to assess limb position
- Astereognosis
- Loss of two point discrimination
- Loss of vibratory sense
- Loss of pain, pressure, heat sensation
Cells of CNS
Neurons
Astrocyte
Oligodendroglia
Microglia
Ependyma
Neurons
Parenchymal unit of CNS
Astrocyte
- Supporting glial cell
- provides trophic maintenance of neurons
- Contributes to BBB
- 10:1
Oligodendroglia
- Cell membrance supplies myelin to multiple axons in CNS
- Myelin in PNS is provided by Schwann cells
Microglia
- Immune cell of CNS
- Derived from circulating monocytes
Ependyma
- Line the CSF-containing ventricular system
- Modified ependyma (choroid plexus) forms CSF
Diseases of the Nervous System
- Developmental Disorders
- Vascular Pathology and Trauma
- Tumors
- Demyelinating Disease
- Degenerative Conditions
Developmental Neuropathology
1-5% of newborns have a CNS anomaly
May be caused by
- genetic defects
- drugs
- toxin/toxicants (often via maternal behavior)
- nutritional abnormalities,
- Infections (TORCH: Toxoplasmosis, Rubella, CMV, Herpes, Zika)
- Perinatal injury
- Most congenital defects are idiopathic
Consequences usually permanent
When is CNS most vulnerable?
During early gestation
- Early lesions are more severe
- Consequences usually permanent
Window of Vulnerability in Brain Morphogenesis
Initial Morphogenesis
Normal Differentiation
Neural Stabilization
Initial Morphogenesis
- Neural Induction/commitment
- Cell Proliferation
- Dysraphism (1st trimester)
Normal Differentiation
- Migration
- Aggregation
- Migration Disorders (2nd trimester)
Neural Stabilization
- Cytodifferentiation
- Synapse formation
- Differentiation disorders (3rd trimester)
Neural Tube Fusion
Lead to Fetal death and dysraphisms (NTDs)
Can be caused by:
- Carcinogens
- Heavy metals
- Hormones
- Antimitotic agents
- Vitamin A excess
- Folic acid deficiency
Craniorachischisis Totalis
- Failure of neural tube closure along it’s full length
- Absence of mature neural tissue and related structures (eg. calvarium)
Incompatible with life
Encephalocele
- Failure of anterior neural tube to fuse
- Incomplete formation of brain and calvarium
- Formation of CSF-filled sac
- Lesions is very severe
Lesser encephaloceles may be compatible with life
Meningocele
Meningoceles contain meninges and CSF, but no formed portion of brain
- Lesions vary widely in severity. If large the likelihood of rupture or infection is substantial
- Moderate lesions may be surgically repaired with survival
- Alpha-fetoprotein is elevated in ALL DYSRAPHISMS
– Test is used in prenatal screening
What do they for in prenatal screening for Meningocele
Alpha-fetoprotein is elevated
in all dysraphisms
Types of Spina Bifida
Spina Bifida Occulta (less sever)
Meningocle (sever)
Myelomeningocele (most sever)
Neuronal Migration
It causes Structural abnormalities (eg. microcephaly, agyria), Heterotopias, and Seizure disorders
Can be caused by
- Antimicrotuble agents
- Heavy metals
- Alcohol
- Pharmaceutical
- Pesticides
- Polychlorinated biphenyls
Differentiation
Causes:
- Structureal abnormalities (subtle)
- Pathway deficits
- Psychomotor deficits
- Epilepsy
- Delayed neurotoxicity
Caused by:
- Alcohol
- Pharmaceuticals
- Heavy metals
- Drugs of abuse
- Dietary deficiency
- Polychlorinated biphenyls
Hydrocephalus
An abnormal buildup of fluid in the ventricles (cavities) deep within the brain.
Synaptogenesis
Casues
- Discrete neurological expression
- Psychomotor retardation
- Delayed neurotoxicity
Caused by
- Alcohol
- Heavy metal
- Industrial pollutants
- Pharmaceuticals
- Drugs of abuse
- Pesticides
Crouzon’s Disease
genetic syndrome in which the seams of the skull fuse in abnormally
Brain Vasculature
Brain is 2% of body weight but receives 15-25% of cardiac output, consumes 20% of oxygen used by body
- Brain blood flow is relatively constant over wide systolic pressures due to autoregulation but shows regional variation of flow according to activity
- Autoregulation fails when systolic BP <50mm Hg
- Arterial supply enter from outside-in
- Arterial vessel reduces diameter rapidly upon entering cortex; may events such as deposition of metastase occur at the gray-white junction
- BBB resides primarily at brain vascular endothelium
- Brain possesses little extracellular space
Where is BBB
resides primarily at the brain
vascular endothelium
Where do the arterial supply enter from?
Outside in
- Autoregulation fails when systolic BP <50mm Hg
What do autoregulation do for the brain?
Keeps the Brain blood flow relatively constant over wide systolic pressures
- shows regional variation of flow according to activity
What do autoregulation do for the brain?
Keeps the Brain blood flow relatively constant over wide systolic pressures
- shows regional variation of flow according to activity
Vasucular Disease of the CNS
- Intracranial Pressure
- Vessel distribution/Circle of Willis
caused by
Aneurysms
Atherosclerosis
Strokes and CVAs
Intracranial pressure
Hematomas and traumatic events
- epidural (middle meningeal artery)
- Subdural (bridging veins)
Aneurysms
3mm-1cm
Most common in the Circle of Willis
- Most common (80%) at branch point of internal carotid artery
- Berry (saccular) aneurysm is rarely congenital; is. acquired with maturity and is present in 2% of adult population
- Atherosclerotic aneurysm are fusiform and commonly involve the basilar artery
- Rupture of either type is commonly fatal (25-50% die with first bleeding); next bleeds are worse
- 3-% of rupture occure with acute increases of intracranial pressure
Most common cause of non-traumatic subarachnoid beeding
What causes the Thunderclap headaches
Aneurysms
Aneurysm is the most common cause of
non traumatic subarachnoid bleeding
Atherosclerotic aneurysms are
Fusiform and commonly involve basilar artery
Cerebral Artery Aneurysm Treatment
Clip placed on the neck of the aneurysm
- Need surgury
Platinum wire is inserted into aneurysm until it is filled with coils => forced thrombus
- No breaking of skull is needed
- Leaking is possible
Flow Diversion Stent
Cerebrovascular Atherosclerosis
Involves larger vessels such as carotid, middle cerebral, basilar arteries
- Embli arising in atherosclerosis is a primary source of cerebral vascular accidents (stoke)
- With advanced therosclerosis, patients suffering a drop in BP may develop infarcts in the absence of occlusion (watershed infarcts)
- Chronic vascular insufficiency contributes to development of dementia (eg,. sleep apnea)
- Small emboli/platelet clots may cause transient ischemic attacks (TIAs); doesn’t cause neuronal death
– anticipate full stoke within several months of TIA
What vessels Cerebrovascular Atherosclerosis involve?
Larger vessels like carotid, middle cerebral, basilar arteries
An advanced atherosclerosis + drop in BP
May develop infarcts in the absence of occlusion (watershed infarcts)
- means blood flow drops
What is the primary source of cerebral vascular accidents (stokes)
Emboli arising in atherosclerosis a primary source of cerebral vascular accidents
What do chronic vascular insufficiency contributes to?
Development of dementia
Stroke
- 65% of stokes (CVA) are ischemic, arising from thrombi or thrombo-emboli from atherosclerosis in brain or heart (valces, atrial fibrillation or vessels)
- Emboli»_space;> thrombi
- 20% of strokes are hemorrhagic, usually involving the lenticulostriate branch of the middle cerebral artery (MCA)
- hemorrhages stokes result from hypertension; often occuring while straining at stool or during sexual activity
- Hemorrhages may be associated with use of thrombolytic drugs or anticoagulant
- Causes upper motor neuron syndorm
- Acute event involve impairment of BBB and edema
What is more serious for stoke Emboli or thrombi
Emboli
What do hemorrhagic stokes involves
lenticulostriate branch of the middle cerebral artery (MCA)
Hemorrhagic stoke result from? associated with?
- Usually result from hypertension; often occur while straining at stool or during sexual activity
- Hemorrhages may be associated with use of
thrombolytic drugs or anticoagulant therapy
What do stokes causes
upper motor neuron syndrome
Ischemic stroke Treatment
Drug management to lyse clot must begin <3.0—4.5 hrs into the event (control lipids)
- TPA iv; aspirin if emergent setting (need to be sure of the type)
- May require carotid endarterectomy or angioplasty/stenting
Hemorrhagic Stoke Treatment
Goal is to control intracranial bleeding and pressure
- Discontinue any blood thinning (Coumadin, Plavix),
- Administer anti-pressor, and drugs to reverse anticoagulant
- May require surgery if bleeding continues and/or damaged vessel identified
- REHAB as early and aggressively as patient can manage
t-Pa causes
Vessels to represses in the cold zone
Ischemic Stroke can be identified through
Radioactive glucose dye
- Blood shunted according to activity and shows the cold zone
Hemorrhagic Stroke; inside
Neurons going to die => liquified necrosis and removed
Neural Trauma
Common cause of death and long term disability (25% of accidental death is due to head trauma)
- Among survival, >20% suffer permanent disability; 5% remain permanently vegetative
Underlying events include
- Hemorrhage
- Movement of brain inside skull with resulting concussion (coup/contre-coup)
- Diffuse axonal injury (DAI; tear axons)
- Infection and EDEMA from altered BBB
BBB disruption may be long standing
Combat or sport injury
(‘closed-head’ injury)
In U.S., most traumatic brain injury results from
vehicular accidents, falls and collisions with objects, criminal assault including child abuse (‘shaken-baby syndrome’)
BBB disruption
may be long standing
Diffuse Axonal Injury
Consequence of acceleration or deceleration of brain, with stretching and/or tearing of axons
- Result in SCATTERED LESIONS both in white and grey matter
- Injury develop over a period of hours to weeks; it is progressive and irreversible
- Occures in 50% of sever head trauma
- 90% of patients with sever head trauma never regain consciousness
- Seen in shaken baby syndrome, TBI, vehicular truama fall, ..
- Difficult to diagnose by imagining
DAI result in
scattered lesions in both white and grey matter
Can DAI recover
Injury develops over a period of hours to weeks; is progressive and irreversible
Epidural Hemorrhage
Middle meningeal artery
- Generally acute, posttraumatic with skull fracture; Rapidly symptomatic
- A medical emergency
Subdural Hemorrhage
Bridging veins
- Generally slow in onset, may become chronic
- May be spontaneous or result of minor trauma
- Most common in elderly
- Headache (‘bursting’)
- Projectile vomiting w/o nausea
- Papilledema
- High mortality without treatment
Which hemorrhage happen posttraumatic event; Acute
Epidural
Which hemorrhage happen in the middle of the meningeal artery
Epidural
Which hemorrhage can become chronic
Subdural
Which hemorrhage happen in the bridging veins
Subdural
Intracranial Pressure (ICP)
Common in any space occupying condition:edema, tumor, hemorrhage, obstruction of CSF, trauma, Infections, etc.
- The higher the ICP the less promising the outcome
- Normal ICP 7-15 mmHg in supine adult; 20-25 mmHg may require treatment
Signs:
- Headache (made worse by coughing, sneezing, bending)
- Vomiiting w/o nausea
- Ocular effects (papilledema)
- Change in consciousness (ICP>50)
- Cheyne-Stokes respiration
- Reflex bradycarida (esp. in children)
Consequences:
- Increased CSF pressure
- Decreased cerebral perfusion
- Ischemia/necrosis
- Brain displacement
- Herniation
Treatment: aggressive
- Must maintain respiration and circulation, diruretics, hyperosmotic agents
ICP Signs
Signs:
- Headache (made worse by coughing, sneezing, bending)
- Vomiiting w/o nausea
- Ocular effects (papilledema)
- Change in consciousness (ICP>50)
- Cheyne-Stokes respiration
- Reflex bradycarida (esp. in children)
ICP Consequences and treatment
Consequences:
- Increased CSF pressure
- Decreased cerebral perfusion
- Ischemia/necrosis
- Brain displacement
- Herniation
Treatment: aggressive
- Must maintain respiration and circulation, diruretics, hyperosmotic agents (draw fluid out of brain)
Unique Features of CNS Tumors
- Do not have morphologically evident premalignant or in situ stages
- Low-grade lesions may infiltrate large areas of brain, with serious clinical consequences, inability to be resected, and poor prognosis
- Anatomic site can influence outcome independent of histological classification (eg. positional malignancy)
- Even highly malignant gliomas rarely spread outside the CNS
CNS Neoplasia
- Meningioma (benign)
- Astrocytoma (malignant)
- Glioblastoma multiforme (malignant)
- Oligodendroglioma
- Medulloblastoma
- Metastasis (most common)
Rule of 70’s
- 70% of primary brain tumors in children are located in the posterior fossa
- 70% of posterior fossa tumors are astrocytomas
- 70% of primary brain tumors in adults are in cerebrum
- 70% of primary brain tumors in adults are glioblastoma multiforme
Signs/Symptoms of Brain Tumors
- Headaches
- Seizures
- Cognitive/personality changes
- Eye weakness
- Nausea/vomiting
- Speech disturbance
- Memory loss
70% of posterior fossa tumors
astrocytomas
70% of primary brain tumors in children
are located in the posterior fossa
70% of primary brain tumors in adults
glioblastoma multiforme
70% of primary brain tumors in adults are in
cerebrum
Clinical Features of Brain Tumors
- Elevated intracranial pressure/compression due to space-occupying lesion
- Cerebral edema
- Irritative effects
- Destruction of local tissue
- Localizing signs reflecting areas of involvement ‘Positional malignancy’
- Hydrocephalus
- Rarely metastasize outside neuroaxis
Meningioma
Arises from the meningeal layer (mostly from the dura mater): Most common benign (90%) intracranial tumor
- 1:1000 individuals, F>M: 40-70 years of age
- Mostly sporadic, some related to radiation to head
Meningioma Signs and treatment
Signs/symptoms of elevated intracranial pressure.
- Most are clinically silent and slow growing
Treatment surgical, when location permits.
- Pre-surgical management includes trans-arterial embolization.
- Chemo not useful due to slow growth.
- Proton beam may be useful
Where do Meningioma arise from
from the meningeal layer (mostly from the dura mater)
What is the most common benign intracranial tumor
Meningioma
Medulloblastoma
- Predominantly in children
- Exclusively cerebellar, may ‘seed’ along the CSF pathway
- Highly malignant
- Highly radiosensitive
- With proper treatment, 5-year survival ~75%
- Arises from neurons of the forming cerebellum
A brain tumor that is most common in 40-70
Meningioma
A brain tumor that is highly malignant
Medulloblastoma
A brain tumor that arises from neurons
Medulloblastoma
- Arises from neurons of the forming cerebellum
Glioblastoma Multiforme
- Arises from astrocytes (astrocytoma GradeIV)
- More common in males; over 50 years of age
- No know cause
- May arise from progression of lower grade astrocytoma or as full GM
- Survival w/o treatment is <6 months
- Survival w treatment ~14 months
Treatment is surgery + radiation; tumor is very resistant to conventional therapy
Brain Metastasis
Account for ~50% of intracranial tumors
Common sites of primary tumor
- lung
- breast
- melanoma
- GI
- Kidney
Often occur at gray-white junction
- May present with paraneoplastic syndromes
Often treated with focused-beam radiation; palliative effect
A brain tumor that arises from astrocytes
Glioblastoma Multiforme
A brain tumor that is more common in adult men
Glioblastoma Multiforme
a brain tumor with unknown cause
Glioblastoma Multiforme
A brain tumor with 75% survival (5 years)
Medulloblastoma
