Neuro Exam 3

Front 1

What are the sequence of events in neuronal development?

Back 1

neural induction -> neural tube formation -> generation of neurons and glia -> axon growth from neurons -> synapses made with targets -> dendrite growth -> myelination

Front 2

What is gastrulation?

Back 2

the process that establishes all three germ layers (ectoderm, mesoderm and endoderm) in the embryo, begins with formation of the primitive streak on the surface of the epiblast which has a primitive node on its cephalic end

Front 3

What is the importance of gastrulation?

Back 3

it defines the midline, A-P and dorsal ventral axes of all vertebrate embryos

Front 4

Describe the formation of the 3 germ layers by the invagination of epiblast cells.

Back 4

occurs when epiblast cells migrate toward the primitive streak, there they detach from the epiblast and slip beneath the primitive pit, once the cells have invaginated, some displace the hypoblast, creating endoderm and others come to lie between the epiblast and form mesoderm, cells remaining in the epiblast form ectoderm, endoderm formed first then mesoderm and ectoderm

Front 5

Describe the formation of the notochord.

Back 5

occurs during gastrulation, essential for the development of the nervous system, a cylinder of mesoderm that condenses at the midline of the mesoderm and extends from the mid-anterior to the posterior aspect of the embryo, generated by the primitive pit -> primitive streak, disappears once early development is complete

Front 6

What is the neuroectoderm?

Back 6

the ectoderm that lies immediately above the notochord, gives rise to the entire nervous system

Front 7

What is the neurulation?

Back 7

formation of the neural plate and neural tube

Front 8

Describe the steps involved in neuralation.

Back 8

notochord sends inductive signals to the overlying ectoderm that cause a subset of neuroectodermal cells to differentiate into neural precursor cells, thickens to form neural plate, lateral margins fold inward forming the neural tube (precursor to brain and spinal cord)

Front 9

Describe the closure of the neural tube.

Back 9

occurs when the neural folds approach each other in the midline, fusion begins in the cervical region (5th somite) and proceeds cranially and caudally, until closure is complete the cephalic and caudal ends communicatre with the amniotic cavity via cranial and caudal neuropores, cranial closes 2 days before posterior one completing neurulation

Front 10

When does neural tube closure occur?

Back 10

early, in the fourth week, day 25 and 27 for anterior and posterior ends respectively

Front 11

What are neural crest cells?

Back 11

formed from cells found at the lateral border of the neuroectoderm that dissociate from the neural tube, it undergoes an epithelium to mesenchymal transition as it leaves the neuroectoderm by active migration and displacement to enter the underlying mesoderm

Front 12

What is the importance of neural crest cells?

Back 12

are the precursor to melanocytes for skin and hair follicles and sensory ganglia, sympathetic and enteric neurons, Schwann cells and ells of the adrenal medulla

Front 13

Describe the organizer experiment.

Back 13

there is transplantation of the upper lip of the blastopore from one amphibian gastrula to another, often led to the induction of a second neural plate, in some instances an entire secondary embryo formed on the flank of the host, the stability of the upper lip of the blastopore to induce the formation of a secondary embryo suggested that this piece of tissue organized development in some fairly general way

Front 14

What role does BMP-4 have on induction of the neuroectoderm?

Back 14

inhibition of BMP-4 signaling induces neuroectoderm, important in neural induction and differentiation, including initial specification of the neural plate and subsequent differentiation of the dorsal part of the spinal cord and hindbrain

Front 15

Describe the inhibition of BMP-4.

Back 15

BMP-4 is secreted throughout the embryonic disc, in presence of BMP-4 mesoderm is ventralized to contribute to kidneys, blood, and body wall mesoderm, it would continue but BMP4 is blocked, this is why the node (dorsal lip of blastopores) is the organizer, inhibition causes cranial mesoderm to dorsalize into notochord, somites and somitomeres

Front 16

What factors antagonize BMP-4?

Back 16

chordin, noggin and follistatin, bind directly to BMPs and prevent their binding to BMP receptors (rescues ectoderm from becoming epidermis

Front 17

Where is Shh found? noggin?

Back 17

Shh is found in notochord and floorplate, noggin found from roofplate as well as the floor plate and notochord

Front 18

Describe the ventral and dorsal signaling in the early CNS development.

Back 18

signals from sonic hedgehog induce the floor plate, floor plate makes Shh too which induces formation of motoneurons and suppresses Pax genes expression (which is done by BMP4)

Front 19

Describe the molecular specification of neuronal phenotypes.

Back 19

there is an integrated network of local signals from the ventral and dorsal spinal cord that specifies sensory relaty neurons, interneurons and motor neurons, interactions between Shh, noggin/Chordin, BMP, RA and FGF leads to either expression or repression of a set of transcprtion factors that distinguish different precursors, these precursors go on to become sensory relay neurons (dorsal), interneurons or motor neurons (ventral)

Front 20

What is spina bifida?

Back 20

is a neural tube defect affecting the spinal region, it consists of a splitting of the vertebral arches and may or may not involve underlying enural tissue

Front 21

What is spina bifida occulta?

Back 21

a defect in vertebral arches that is covered by skin and usually does not involve underlying neural tissue, occurs in lumbosacral region and is usually marked by a patch of hair overlying the affected region, due to a lack of fusion of vertebral arches, affects about 10% of otherwise normal people, spinal cord is intact

Front 22

What is spina bifida cystica?

Back 22

severe neural tube defect, neural tissue and/or meninges protrude thorugh a defect in the vertebral arches and skin to form a cystlike sac, result in neurological deficits, not associated with mental retardation

Front 23

What is meningocele?

Back 23

a spina bifida in which only fluid-filled meninges protrude thorugh the defect

Front 24

What is meningomyelocele?

Back 24

neural tissue is included in the sac that protrudes through the defect

Front 25

What is myeloschisis or rachischisis?

Back 25

a spina bifida with neural folds that do not elevate but remain as a flattened mass of neural tissue, results in exposure of neural tissue that often becomes necrotic, the most severe type of abnormality

Front 26

Can spina bifida cystica be diagnosed prenatally?

Back 26

yes, by ultrasound and by determination of alpha-fetoprotein levels in maternal serum and amniotic fluid

Front 27

What is anencephaly?

Back 27

neural tube defect in which the cranial neural folds fail to close leading to tissue degernation and little or no formation of higher brain centers, cerebral cortex, is lethal, 70% of defects can be prevented by daily materanal use of folic acid beginning 2 to 3 months prior to conception and continuing throughout pregnancy

Front 28

What are some important facts about NTDs?

Back 28

1. is the most common human malformation incidence, of 1-8/1000 live births
2. etiology-failure of closure of the neural tube
3. multifactorial-chromosomal, diabetes, teratogens (such as medications for epilepsy), hyperthermia
4. prenatal diagnosis-alpha-fetoprotein (S-100), ultrasound (anencephaly)
5. prevention-folic acid (72% reduction)

Front 29

What is the significance of folic acid?

Back 29

reduces the incidience of NTDs by as much as 70% if 0.4 mg is taken daily beginning 2 months prior to conception

Front 30

What are some examples of infection agent teratogens that affect neuronal development?

Back 30

rubella (eye and ear defects), cytomegalovirus (eye defect, microcephaly), toxoplasmosis (hydrocephalus)

Front 31

What are some examples of physical agents/temperature teratogens that affect neuronal development?

Back 31

X-rays (spina bifida), hyperthermia (neural tube defects)

Front 32

What are some examples of drug teratogens that affect neuronal development?

Back 32

epilepsy medication (neural tube defects), vitamin A overdose (neural tube defects), folic acid antagonists (neural tube defects), alcohol (mental retardation)

Front 33

What are the different types of malformation that may occur during different time periods of development?

Back 33

weeks 0-3 usually leads to death of embryo, weeks 3-8 (organ formation) usually lead to malformation of embryo (heart defect), weeks 8-38 (growth and maturation of organ systems) may lead to functional disturbances of fetus (mental retardation)

Front 34

When is the risk of a congenital anomoaly greatest?

Back 34

during weeks 3-8, at about week 5 is at a max, then DEC with an INC in age

Front 35

What are the physical representations of fetal alcohol syndrome?

Back 35

thin upper lip, short palpebral fissures, flat nasal bridge, short nose, elongated philtrum, includes structural defects, growth deficiency and mental retardation

Front 36

Describe the development of the eye.

Back 36

placode and neural tube form the eye, optic vesicles from outpocketings of the forebrain, these vesicles come in contact with the ectoderm and induce changes for lens formation, optic vesicle then forms optic cup, then invaginats forming choroid fissure (where hyaloids artery enters the eye), lips of the choroid fissure fuse and eventually forms pupil, cells of surface ectoderm forms lens placode

Front 37

What is the significance of the lens placode?

Back 37

it invaginates and develops into the lens vesicle, which eventually forms the lens

Front 38

What is the significance of the optic cup?

Back 38

forms all the layers of the retina as well as the RPE and parts of the iris and ciliary body, muscles of the iris and ciliary body are formed by mesenchyme that invades the optic cup, this mesenchyme also forms the sclera and choroid

Front 39

Where does the cornea come from?

Back 39

cornea comes from surface ectoderm and the underlying mesenchyme, not the lens placode and optic cup, comes from a layer of surface ectoderm, the stroma and an epithelial layer bordering the anterior chamber

Front 40

What is coloboma iridis?

Back 40

defect in the eye due to a persistent choroid fissure (incomplete closure), usually restricted to the iris

Front 41

Describe the development of the ear.

Back 41

comes from the otic placode/otic vesicle

Front 42

What does the otic placode do?

Back 42

forms the membranous labyrinth and sensory neurons of CN VIII (inner ear), very slow development, otic vesicle detaches from surface ectoderm, divides into a ventral component (saccule and cochlear duct) and dorsal (utricle, semicircular canals and endolympahtic duct)

Front 43

Where does the middle ear cavity and ossicles come from?

Back 43

endoderm, cavity comes from the adjacent 1st pharyngeal pouch lined by endoderm, middle ear ossicles come from the mesenchyme of the 1st and 2nd arches which invade between the pouch and cleft

Front 44

Where does the external auditory canal come from?

Back 44

comes from the adjacent 1st pharyngeal cleft between the 1st (M and I) and 2nd (S) pharyngeal arches

Front 45

Where does the auricle come from?

Back 45

develops from auricular hillocks which are blocks of mesenchyme from the 1st and 2nd arches, defects in the auricle are often associated with other congenital malformations

Front 46

What are some examples of physical agents/temperature teratogens that affect neuronal development?

Back 46

X-rays (spina bifida), hyperthermia (neural tube defects)

Front 47

What are some examples of drug teratogens that affect neuronal development?

Back 47

epilepsy medication (neural tube defects), vitamin A overdose (neural tube defects), folic acid antagonists (neural tube defects), alcohol (mental retardation)

Front 48

What are the different types of malformation that may occur during different time periods of development?

Back 48

weeks 0-3 usually leads to death of embryo, weeks 3-8 (organ formation) usually lead to malformation of embryo (heart defect), weeks 8-38 (growth and maturation of organ systems) may lead to functional disturbances of fetus (mental retardation)

Front 49

When is the risk of a congenital anomoaly greatest?

Back 49

during weeks 3-8, at about week 5 is at a max, then DEC with an INC in age

Front 50

What are the physical representations of fetal alcohol syndrome?

Back 50

thin upper lip, short palpebral fissures, flat nasal bridge, short nose, elongated philtrum, includes structural defects, growth deficiency and mental retardation

Front 51

Describe the development of the eye.

Back 51

placode and neural tube form the eye, optic vesicles from outpocketings of the forebrain, these vesicles come in contact with the ectoderm and induce changes for lens formation, optic vesicle then forms optic cup, then invaginats forming choroid fissure (where hyaloids artery enters the eye), lips of the choroid fissure fuse and eventually forms pupil, cells of surface ectoderm forms lens placode

Front 52

What is the significance of the lens placode?

Back 52

it invaginates and develops into the lens vesicle, which eventually forms the lens

Front 53

What is the significance of the optic cup?

Back 53

forms all the layers of the retina as well as the RPE and parts of the iris and ciliary body, muscles of the iris and ciliary body are formed by mesenchyme that invades the optic cup, this mesenchyme also forms the sclera and choroid

Front 54

Where does the cornea come from?

Back 54

cornea comes from surface ectoderm and the underlying mesenchyme, not the lens placode and optic cup, comes from a layer of surface ectoderm, the stroma and an epithelial layer bordering the anterior chamber

Front 55

What is coloboma iridis?

Back 55

defect in the eye due to a persistent choroid fissure (incomplete closure), usually restricted to the iris

Front 56

Describe the development of the ear.

Back 56

comes from the otic placode/otic vesicle

Front 57

What does the otic placode do?

Back 57

forms the membranous labyrinth and sensory neurons of CN VIII (inner ear), very slow development, otic vesicle detaches from surface ectoderm, divides into a ventral component (saccule and cochlear duct) and dorsal (utricle, semicircular canals and endolympahtic duct)

Front 58

Where does the middle ear cavity and ossicles come from?

Back 58

endoderm, cavity comes from the adjacent 1st pharyngeal pouch lined by endoderm, middle ear ossicles come from the mesenchyme of the 1st and 2nd arches which invade between the pouch and cleft

Front 59

Where does the external auditory canal come from?

Back 59

comes from the adjacent 1st pharyngeal cleft between the 1st (M and I) and 2nd (S) pharyngeal arches

Front 60

Where does the auricle come from?

Back 60

develops from auricular hillocks which are blocks of mesenchyme from the 1st and 2nd arches, defects in the auricle are often associated with other congenital malformations

Front 61

Where does the eardrum come from?

Back 61

ectodermal epithelial lining at the bottom of the auditory meatus, endodermal epithelial lining of the tympanic cavity and an intermediate layer of CT that forms the fibrous stratum

Front 62

What do Hox genes do?

Back 62

regulate segmentation of the neuraxis, are important for patterning the embryonic axis, establishing different regions of the brain, determining the origin and type of gut derivatives, patterning the limbs and other similar phenomena, expressed in the notochord, prechordal plate and neural plate, segragates the brain into forebrain, midbrain and hindbrain regions, also guides differentiation of the embryo into distinct segments that give rise to the head, thorax and abdomen

Front 63

Describe the development of the brain ventricles.

Back 63

early in gestation the neural tube becomes subdivided into the presencephalon (anterior end of embryo), mesencephalon and rhombencephalon, spinal cord differentiates from the more posterior region of the neural tube, bending leads to can shape, further development distinguishes the telencephalon and diencephalon from the prosencephalon, the metencephalon and myelencephalon derive from the rhombencephalon, these subdivisions give rise to the rudiments of the major functional subdivisions of the brain while the spaces they enclose eventually form the ventricles of the mature brain

Front 64

What are the different flexures of the neural tube?

Back 64

the crook found at the anterior end of the tube, two types:
1. cephalic flexure-balloons out to form the prosencephalon giving rise to the forebrain, midbrain (mesencephalon) forms as a bulge above the cephalic flexure
2. cervical flexure-more caudal, forms the bindbrain (rhombencephalon), caudal to this flexure is the precursor of the spinal cord

Front 65

What is hydrocephalus?

Back 65

is incomplete closure of the cranial sutures, CSF accumulates and pressure from this accumulation enlarges the head, thinning the bones of the skull and cerebral cortex, usually due to a block in the circulatory pattern of the fluid, which occurs in the cerebral aqueduct of Sylvius

Front 66

Describe the development of the pituitary gland.

Back 66

develops from neural tube as a downward extension of the diencephalon (infundibulum) (gives rise to the posterior lobe composed of neurological cells and fibers from hypothalamus) and an ectodermal outpocketing of the stomodeum immediately in front of the buccopharyngeal membrane known as Rathke’s pouch (forms the anterior lobe)

Front 67

Describe the development of the spinal cord.

Back 67

neuroepithelial cells give rise to neuroblasts, neuroblasts form the mantle layer which forms the gray matter and extend their fibers to make the marginal layer which forms the white matter, neuroblasts are continually added to the mantle layer and form the basal (motor), alar (sensory) and floor (passageway for fibers to reach the other side) plates

Front 68

Describe positional changes of the cord.

Back 68

at 3 months, spinal cord extends the entire length of the embryo and spinal nerves pass through the intervertebral foramina at their level of origin, with INCing age vertebral column and dura lengthen more rapidly than the neural tube and the terminal end shifts to a higher level, as a result spinal nerves run obliquely from their segment of origin in the spinal cord to the corresponding level of the vertebral column

Front 69

What are the different sources of neurons/glia?

Back 69

neural tube (ventricular zone), placodes, neural crest, stem cells

Front 70

What is the ventricular zone?

Back 70

the precursor cells of neurons are found here, innermost cell layer surrounding the lumen of the neural tube, region of extraordinary mitotic activity

Front 71

Describe neurogenesis in the ventricular zone.

Back 71

the entire neuronal complement of the adult brain is produced during a time window that closes before birth, the precursor cells here undergo a stereotyped pattern of cell movements as they progress through the mitotic cyctle, leading to the formation of either new stem cells or postmitotic neuroblasts that differentiate into neurons

Front 72

What is the difference between new stem cells and neuroblast generation?

Back 72

new stem cells arise from symmetrical divisions of neuroectodermal cells, neuroblasts are generated from cells that divide asymmetrically

Front 73

Describe the migration of the neural crest.

Back 73

can go to somites, notochord or dorsal aorta, crest cells from the trunk region leave the nural folds and migrate via a dorsal pathway through the dermis where they enter the ectoderm for melanocytes and a ventral pathway through the anterior half of each somite to become sensory ganglia, also migrate from cranial neural folds contributing to the craniofacial skeleton

Front 74

What structures do the neural crest cells go to and what type of cells do they become there?

Back 74

DRG (unipolar neuron), pigment cells, sympathetic ganglion (multipolar neuron), developing adrenal gland (chromaffin cells), prevertebral plexus and plexus in the gut wall (parasympathetic (submucosal) plexus in gut)

Front 75

Where are the different types of mesenchyme found and what do they give rise to in head/face development?

Back 75

mesodermal mesenchyme is found in the myelencephalon and mesencephalon while neural crest mesenchyme is found in the pharyngeal branches, optic vesicle and diencephalon, mesodermal mesenchyme gives rise to the face while neural crest mesenchyme gives rise to the face skull

Front 76

What contribution does the neural crest have on cranio-facial development?

Back 76

pharyngeal branches give the head and neck their typical appearance in the 4th week, patterning of the skeletal elements of the pharyngeal arches is regulated by gene expression in pharyngeal pouch endoderm

Front 77

What are the different types of trunk crest and what cranial crest do they give rise to?

Back 77

1. spinal ganglia-cranial ganglia (V, VII, IX, X)
2. sympathetic ganglia-parasympathetic ganglia
3. glial cells of peripheral nerves-glial cells of peripheral nerves leptomeninges
4. melanocytes-melanocytes
5. adrenal medulla-carotid body, thyroid, skeleton (cranial bone and cartilage), CT (dermis, odontoblasts), muscle (ciliary, vascular)

Front 78

What is an embryonic stem cell?

Back 78

self-renewing, can give rise to all tissue and cell types (including germ cells)

Front 79

What is somatic stem cell?

Back 79

self-renewing, can give rise to full range of diploid, tissue-specific cell classes

Front 80

What is neural stem cell?

Back 80

self-renewing, can give rise to any diploid cell type in the CNS or PNS

Front 81

What is neural progenitor cell?

Back 81

no self-renewal, can give rise to only one class of neurons

Front 82

Describe the lineage concerning the generation of neurons and glia.

Back 82

1. neural tube -> neuroepithelium and mesenchyme
2. mesenchyme -> microglia cells
3. neuroepithelium -> apolar neuroblast, glioblast (spongioblast) and ependyma and epithelium of choroid plexus
4. apolar neuroblast -> bipolar neuroblast -> unipolar neuroblast -> multipolar neuroblast
5. glioblast -> astroblast (-> protoplasmic astrocytes and fibrous astrocytes) and oligodendroblast (-> oligodendrocytes)

Front 83

What cells perform myelination?

Back 83

Schwann cells in the PNS and oligodendrocytes in the CNS

Front 84

What determines cell diversity: lineage or environment?

Back 84

two different hypotheses:
1. cells acquire diverse fates while still at the precursor stage, relying primarily on information intrinsic to each cell, subsequent divisions result in the proliferation of these cells which differentiate according to their lineage
2. cells are descended from a pleuripotential precursor, diversity being generated among daughter cells by specific signals from other cells, experimental evidence in vertebrates favors this model

Front 85

Describe the role of different signaling molecules in turning neural crest progenitors into different phenotypes.

Back 85

cell signaling during migration of neural crest cells influences progenitor identity and termainl differentiation, each signal is available along a specfici migratory route taken by subsets of enural crest cells

Front 86

What are the different cell signals that can affect neural crest progenitors and what effect do they have?

Back 86

1. leukocyte inducing factor-turns neural crest progenitor into sensory neuron
2. FGF2-turns neural crest progenitor into sympathetic progenitor which can then be affected by NGF (to becomre adrenergic neurons) or ciliary neurotrophic factor (cholinergic neurons)
3. stem cell factor-turns progenitor into melanocyte
4. glucocorticoids-turns progenitor into chromaffin cell progenitor which becomes chromaffin cells

Front 87

What are radial glia?

Back 87

long processes that guides neuron migration, affect many neorblasts that migrate long distances within the CNS including those in the cerebral cortex, cerebellum and hippocampus, also thought to be neuronal progenitor cells in the developing CNS

Front 88

Describe the course of the radial glia.

Back 88

found in forebrain and radiates from the ventricle to the pial surface, there are also non-radially migrating cells that run perpendicular to the glial processes

Front 89

What are some examples of neurons that migrate?

Back 89

neural crest, mesencephalic nucleus of the trigeminal nerve, olfactory placode/hypothalamus (GnRH-neurons), oculomotor neurons (exchange across the midline)

Front 90

What are growth cones?

Back 90

a specialized structure at the tip of the extending axon, highly motile, explore the extracellular environment determining the direction of growth and then guiding the extension of the axon in that direction, have filopodia that extend from lamellipodium

Front 91

Why are growth cones important?

Back 91

activity is key for the construction of pathways and circuits in the developing brain, once a cone reaches and recognizes an appropriate target it is gradually transformed into either a presynaptic ending for an axon or the terminal domain of a dendrite

Front 92

What role do the filapodia on growth cones play?

Back 92

filopodia rapidly form and disappear from the terminal expansion like fingers reaching out to sense the environment

Front 93

What role do the cytoskeletal elements in growth cones play?

Back 93

growth cone motility reflects rapid, controlled rearrangement of cytoskeletal elements, these elements include actin (which regulates changes in lamellipodial and filopodial shape for directed growth) as well as the microtubules (responsible for the elongation of the axon itself)

Front 94

What happens during attractive and repulsive cues in the growth cone?

Back 94

G-actin is incorporated into F-actin at the leading edge of the filopodium in response to attractive cues, repulsive cues support disassembly and retrograde flow of G-actin toward the lamellipodium

Front 95

What role do the microtubules play in the growth cone?

Back 95

organized microtubules make up the cytoskeletal core of the axon, more broadly dispersed microtubule subunits are found at the transition between the axon shaft and the lamellipodium

Front 96

What regulates the assembly and disassembly of subunits to filaments or tubules?

Back 96

actine and tubulin-binding proteins, this process is influenced by changes in intracellular Ca2+ via voltage regulated Ca2+ channels as well as transient receptor (TRP) channels

Front 97

What happens to growth cone morphology during crucial decision points?

Back 97

growth cones change their morphology at crucial decision points (moments when cones encounter a potential target and extend numerous filopodia), suggest an active search for appropriate cues to direct subsequent growth

Front 98

What are some non-diffusible signals for axon guidance?

Back 98

1. on cell surface-cell adhesion molecules (CAMs), include neuronal, glial and cadherins
2. on extracellular matrix-laminin, collagen, fibronectin, there receptors are integrins

Front 99

What are some diffusible signals for axon guidance?

Back 99

netrins (commissures), ephrins (retinotectal map), and semaphorins (chemorepellent, can also be anchored to cell surfaces)

Front 100

What are the different types of adhesion molecules?

Back 100

laminin (found in the ECM with fibronectin and collagen), fibronectin, integrin, and CAMs

Front 101

What do the ECM cell adhesion molecules do?

Back 101

are secreted by the cell itself or by its neighbors, after secretion form polymers and create a more durable local EC substance

Front 102

What do integrins do?

Back 102

bind specifically to ECM cell adhesion molecules, do not have kinase activity, binding to ECM cell adhesion molecules triggers a cascade of events that generally stimulates axon growth and elongation

Front 103

What do the CAMs do?

Back 103

present on growing axons and growth cones as well as surrounding cells or targets, function as ligands and receptors, used in bundling of groups of axons as they grow, important determinants of final target selection in the transition from gworing axon to synapse

Front 104

Describe the ability of growth cones to respond to multiple cues.

Back 104

they can, react with chemoattractants and chemorepellants, chemoattractants can operate from a distance and reorient growth toward the source of the cue often by acting on a pioneer growth cone that sets out a course distinct form the fasiculated followers, chemoreulsive signals can also act from a distance, act at regions where axons must defasiculate from a nascent nerve in order to change their trajectory or avoid an inappropriate target

Front 105

What do trophic signals do?

Back 105

they support the furterh growth and differentiation of the axon and its parent nerve cell

Front 106

What are netrins?

Back 106

chemoattractant, they attract some axons, product of a gene that influenced axon growth and guidance, has no known enzymatic activity and thus must interact with the other proteins with catalytic activity

Front 107

Describe netrin/slit commissural guidance.

Back 107

netrin chemotropically regulate pathway formation in the developing spinal cord, commissural neurons send axons to the ventral region of the spinal cord including the floor plate, netricn and slit oppose each other at the ventral midline of the spinal cord, ensures that the axons relaying pain and temperature via the anterolateral pathway cross the midline at appropriate levels of the spinal cord and remain on the contralateral side until they reach their targets in the thalamus

Front 108

What are stripe assays?

Back 108

show the differences between anterior and posterior tectum, temporal retinal axons when presented with a choice of cell membranes derived from anterior or posterior tectal regions as a substrate, grow exclusively on anterior membranes, avoiding membranes derived from the wrong region of the tectum, the positive interactions are probably due to INC adhesion of the growth cones to the substrate whereas the failure to grow into inappropriate regions may result form repulsive interactions that tend to collapse the growth cones, temporal axons prefer to grown on anterior membranes, nasal retinal aoxons grow equally well on both stripes

Front 109

How do ephrins establish gradients fro retinotopic maps?

Back 109

posterior retinal axons project to the anterior tectum and anterior retinal axons to the posterior tectum, when the optic nerve of a frog is surgically interrupted the axons regenerate with the appropriate specificity

Front 110

What do complementary gradients of Eph receptors and ephrins lead to?

Back 110

lead to differential affinities and topographic mapping, retinal growth cones with a high concentration of Eph receptors would be more likely to recognize a lower concentration of ligand whereas a growth cone with low Eph receptor concentration would recognize a higher concentration of ligand

Front 111

What is the neurotrophic hypothesis?

Back 111

the idea that developing neurons compete for a limited supply of trophic factors secreted by their targets, those that receive factors survive those that don’t die

Front 112

What happens during manipulation of targets?

Back 112

it changes neuronal survival, target-derived trophic support regulates survival of related neurons, spinal cord generates an excess of neurons prior to differentiation and innervation of the limb, surgery to remove limb depletes the pool of motor neurons that would have innervated the missing extremity, adding an extra limb rescues early-generated neurons that normally would have died leading to an abnormally large number of limb motor neurons on the side related to the extra limb (these are recruited from the pool of cells overproduced rather than generated de novo

Front 113

Describe the neurotrophin receptors.

Back 113

there are TrkA, B and C receptors (which are specific for neurotrophins) and p75 receptors (these bind all types of neurotrophins), for the tyrosine kinases (Trk) there is some degree of cross-activation under certain conditions, are high affinity, p75 is low affinity, confers the ability to respond to a broad range of neurotrophins

Front 114

What are the different families of trophic factors?

Back 114

neurotrophins (NGF-like factors), GDNF-like trophic factors, FGF (fibroblast growth factors) and IGFs (insulin-like growth factors)0

Front 115

What are some sources of trophic factors?

Back 115

PNS and CNS, can be anterograde or retrograde

Front 116

What type of trophic factors do distinct DRG neurons react with?

Back 116

functionally distinct DRG neurons depend on different trophic factors, neurotrophins have distinct effects on different target neurons, distinct classes of peripheral somatosensory receptors and the DRG cells that give rise to these sensory ending depend on different trophic factors in specific target tissues

Front 117

What are different DRG neurons that react with different trophic factors?

Back 117

1. hair follicle-NT4/5
2. merkel disk-BDNF
3. free nerve ending-NGF
4. muscle spindle-NT3

Front 118

Describe the elimation of polyneural innervation.

Back 118

the number and pattern of synapses is adjusted during the first few weeks of postnatal life in the mammalian peripheral nervous system, in muscles and in peripheral ganglia each axon innervates a large number of target cells at birth than in maturity, rudimentary multiple innervation eliminated after birth, but complexity and size of arborization INC (get more and more terminal branches and synaptic endings

Front 119

What is the importance of the elimination of polyneural innervation

Back 119

leads to removal of immature contacts from all but one of a few axons of each target and the focus on fewer target cells by a progressively INCing amount of synaptic machinery for each axon that remains

Front 120

What are neurites?

Back 120

used to describe neuronal branches when it is not known whether they are axons or dendrites

Front 121

What is the effect of the neurotrophin NGF on the outgrowth of neurites and survival of neurons?

Back 121

in the absence of NGF there are few if any neuronal branches that grow out into the medium, adding NGF stimulates a halo of neurite outgrowth from the ganglion cells, NGF influences the survival of newborn rat sympathetic ganglion cells, these cells depend on NGF

Front 122

What is the effect of NGF on PC12 cells?

Back 122

when NGF is added to a medium of PC12 cells, leads to differentiation of PC12 cells, leads to formation of long thread like fibers

Front 123

What is the importance of signaling cascades?

Back 123

give the signal for survival (Trk receptor) or apoptosis (P75NTR receptor) for cells, Trk is via PLC-gamma and Ras cascade which leads to activation of CREB, p75 acts via TRAF5 and NRIF to activate NF-kappaB, BAD and caspase (leading to DNA cleavage)

Front 124

What signaling cascades does the Trk receptor activate?

Back 124

1. PI-3 kinase which activates PKB and Akt kinase which leads to cell survival
2. ras-activates kinases and MAP kinases which leads to neurite outgrowth and neuronal differentiation
3. PLC-leads to activation of IP3 (-> Ca2+ release) and DAG (-> PKC) which leads to activity-dependent plasticity

Front 125

What signaling cascades does the p75 receptor activate?

Back 125

1. SC1-cell cycle arrest
2. NADE-cell death
3. RhoA-neurite growth

Front 126

How does experience/environment influence formation of neural circuits?

Back 126

example: visual system development, ocular dominance columns, binocular vision, importance in other sensory and motor development

Front 127

Describe transneuronal transport.

Back 127

a neuron in the retina is shown taking up a radioactive amino acid (usually proline), incorporating it into proteins and moving the proteins down the axons and across the extracellular space between neurons (via anterograde axonal transport), this process is repeated in the thalamus and eventually label accumulates in the thalamocortical terminals in layer 4 of the primary visual cortex

Front 128

What are ocular dominance columns?

Back 128

an alternating series of eye-specific domains in cortical layer 4 from afferent terminals, can be visualized by injecting tracers such as radioactive amino acids into one eye and following their path

Front 129

Describe the course of the labeled amino acids.

Back 129

the labeled amino acids travel through the optic tract, cross the lateral geniculate nucleus and through the optic radiation, terminates in layer 4 of the primary visual cortex, found in ipsilateral but not in contralateral retinal ganglion cells axons

Front 130

What role does transynaptic transport have on which regions are labelled

Back 130

due to the transynaptic transport of the label, geniculocortical terminals related to the injected eye are visible as a pattern of bright stripes, the dark areas are the zones occupied by geniculocortical terminals related to the other eye

Front 131

Describe the development of ocular dominance columns.

Back 131

during early development, axons cross over multiple layers, as development continues, each of these axons become specialized to a specific layer and branch more and more until a point is reached (at 13 weeks) when each layer has only one axon innervating it

Front 132

What happens during the critical period when there is light deprivation?

Back 132

it reduces layer IV input, terminal arborizations of lateral geniculate nucleus axons in the visual cortex can change rapidly in response to monocular deprivation during the critical period, after only a week of monocular deprivation axons terminating in layer 4 of the primary visual cortex from LGN neurons driven by depreived eye have greatly reduced numbers of branches compared with those form the open eye, deprivation for longer periods does not result in appreciably larger changes in the arborization of geniculate axons

Front 133

Describe the test involved in looking at the effect of age of eyelid closure on the distribution of cortical neurons driven by stimulation of both eyes?

Back 133

histogram plots the number of cells that fall into one of the seven ocular dominance categories, defined based on the freq. of AP activity elicited from visual cortical neurons following illumination in the relevant eye, light is shined into both wide-open eyes to elicit responses in the visual cortex

Front 134

What happens in normal adults?

Back 134

cells in group 1 were activated exclusicely by the contralateral eye, cells in group 7 by ipsilateral eye, there were no cells that were not responsive to light stimulation in the retina

Front 135

What happens in monocular deprivation in kitten?

Back 135

one eye of a newborn kitten was closed from 1 week to 2.5 months, then allowed to mature, deprivation was relatively short, light presented to the open but transiently deprived eye elicited no electrical responses in visual cortical neurons, the only visually responsive cells responded to the ipsilateral eye

Front 136

What happens in monocular deprivation in an adult?

Back 136

a much longer period of monocular deprivation in an adult cat showed little effect on ocular dominance, although overall cortical activity is diminished, most of the responsive cells were driven by both eyes, in addition some cells are uniquely or mostly responsive to the deprived eye

Front 137

What does the experiment for monocular deprivation for 3 vs. 6 days show?

Back 137

shows the consequences of a short period of monocular deprivation at the height of the critical period in the cat, just 3 days of deprivation produced a significant shift of cortical activation in favor of non-deprived eye, six days of deprivation produced a shift of cortical activation in favor of the non-deprived eye that is almost as complete as that elicited by 2.5 months of deprivation

Front 138

What is the effect of strabismus induced during the critical period on ocular dominance?

Back 138

the number of binocularly driven cells (groups 3, 4, 5) is sharply DEC as a consequence of strabismus, most of the cells are driven exclusively by stimulation of one eye or the other, this enhanced segregation of the inputs presumably results from the greater discrepancy in the patterns of activity between the two eyes as a result of surgically interfereing with normal conjugate vision, this pathological state is thought to enhance the relative degree of correlation within inputs from each eye, and DEC the possibility of correlation between eye inputs

Front 139

What is Hebb’s postulate?

Back 139

hypothesis that states that the coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthens the synaptic connection between them, originally formulated to explain the cellular basis of learning and memory, it implies that synaptic terminals strengthened by correlated activity will be retained or sprout new branches, whereas those terminals that are persistently weakened by uncorrelated activity will eventually los their hold on the postsynaptic cell

Front 140

Describe how Hebb’s postulate is represented as it might operate during development of the visual system.

Back 140

the cell represents a postsynaptic neuron in layer 4 of the primary visual cortex, early in development, inputs from the two eyes converge on single postsynaptic cells, the two sets of presynaptic inputs have different patterns of electrical activity, each pattern is more correlated with terminals driven by the same eye than that driven by the opposite eye

Front 141

In this example, how do the right and left eye inputs differ?

Back 141

the three left eye inputs are better able to activate the postsynaptic cell, these inputs cause the postsynaptic cell to fire a pattern of Ap that follows the pattern seen in the input, as a result, the activity of the presynaptic terminals and the postsynaptic neuron is highly correlated, according to Hebb’s postulate these synapses are therefore strengthened, the inputs from the right eye carry a different pattern of activity that is less well correlated with the majority of the activity elicited in the postsynaptic cell, these synapses gradually weaken and are eventually eliminated while the correlated inputs form additional synapses

Front 142

What is imprinting?

Back 142

a rapid and permanent form of learing that occurs in reponse to early experience

Front 143

What did Konrad Lorenz do in imprinting experiments?

Back 143

showed that goslings follow the first large, moving object they see and hear during their first day of life, they can imprint on a wide range of animate and inanimate objects, in many mammals auditory and visual systems are poorly developed at birth and maternal imprinting relies on olfactory and/or gustatory cues, experiments shows that many complicated behaviors, emotional responses and other predilections are well established in the nervous system prior to any significant experience and that the need for certain kinds of early experience for normal development is predetermined

Front 144

What is the critical period?

Back 144

temporal windows where environmental factors are especially influential in early life, allows for the individual to adapt to and are influenced by the particular circumstances of an individual’s environment, specific stimuli only work during the critical period and will not work outside of it, some last long, others are short, a given behavior requires a specific environmental influence in order to develop normally

Front 145

What human behaviors fall to critical periods?

Back 145

language, vision, auditory, somatic sensory and olfactory systems

Front 146

Is the brain hard-wired?

Back 146

the mature brain is not entirely hard-wired, some forms of neuronal plasticity extend into adulthood including short and long term synaptic plasticity

Front 147

What is short term plasticity?

Back 147

synaptic connectivity between neurons is a dynamic entity that is constantly changing in response to neural activity and other influences, most short term affect the amount of neurotransmitter released from presynaptic termainls in response to a presynaptic AP, usually enhance it and are caused by persistent actions of Ca2+ ions within the presynaptic terminal

Front 148

What are the different types of short term plasticity?

Back 148

facilitation, augmentation and potentiation, also synaptic depression

Front 149

What happens when a train of stimuli is applied to a presynaptic motor nerve?

Back 149

it produces changes in EPP amplitude causing it to DEC, once stimulus is removed and given some time to rest, EPP returns to normal with a single stimulus

Front 150

What are the steps of dynamic changes in transmitter release caused by the interplay of severl forms of short term plasticity?

Back 150

facilitation (INC release) and augmentation (DEC release back to normal levels) of the EPP occurs at the beginning of the stimulus train and are followed by a pronounced depression of the EPP, potentiation (INC from the <1 area) beings late in the stimulus train and persists for many seconds after the end of the stimulus, leading to post-tetanic potentiation

Front 151

What is synaptic facilitation?

Back 151

a rapid INC in synaptic strength that occurs when two or more APs invade the presynaptic terminal within a few milliseconds of each other, a result of prolonged elevation of presynaptic Ca2+ levels following synaptic activity

Front 152

What is synaptic depression?

Back 152

opposes facilitation, causes neurotransmitter release to decline during sustained synaptic activity, depression depends on the amount of neurotransmitter that has been released, lowering external Ca2+ conc. causes the rate of depression to be slowed, amount of depression is proportional to the amount of transmitter released from the presynaptic terminal

Front 153

What elicits potentiation and augmentation?

Back 153

elicited by repeated synaptic activity and serve to INC the amount of transmitter released from presynaptic terminals, both enhance the ability of incoming Ca2+ to trigger fusion of synaptic vesicles with the plasma membrane but they work over different time scales (few seconds for augmentation while augmentation outlasts the tetanus)

Front 154

What is habituation?

Back 154

a DEC in the response to a benign stimulus when that stimulus is presented repeatedly, reduced mobilization of transmitter vesicles to the active zone

Front 155

What is sensitization?

Back 155

an enhanced response to a wide variety of stimuli after the presentation of an intense or noxious stimulus

Front 156

What is short-term presynaptic facilitation of synaptic transmission?

Back 156

signal transduction cascade involving neurotransmitters, second messengers and ion channels

Front 157

What is long-term presynaptic facilitation of synaptic transmission?

Back 157

changes in gene expression, protein synthesis (PKA and MAPK translocate to nucleus, PKA phosphorylates CREB, activation of transcription), INC in number of synapses

Front 158

What is sensitization?

Back 158

allows an animal to generalize an aversive response elicited by a noxious stimulus to a variety of other, non-noxious stimuli

Front 159

Describe sensitization in the snail, Aplysia.

Back 159

sensitization of gill withdrawal is elicited by pairing a strong electrical stimulus to the animal’s tail with another light touch of the siphon, this stimulus elicits a strong withdrawal of the gill bec the noxious stimulus sensitizes the gill withdrawal reflex to light touch, remains enhanced for an hour but if repeatedly done can enhance for weeks

Front 160

Describe the mechanism involved in sensitization in the snail Aplysia.

Back 160

touching the siphon skin activates sensory neurons that excite interneurons and gill motor neurons, a shock to the animal’s tail sitmulates modulatory interneurons that alter synaptic transmission between siphon sensory neurons and gill motor neurons resulting in sensitization

Front 161

Describe the presynaptic mechanism of sensitization.

Back 161

1. serotonin is released by facilitatory interneurons and binds to G-protein-coupled receptors on presynaptic terminals of siphon sensory neurons
2. INC production of cAMP
3. cAMP binds to PKA
4. PKA phosphorylates several proteins probably including K+ channels
5. this reduces the probability that the K+ channels open during a presynaptic AP, this prolongs the presynaptic AP thereby opening more presynaptic Ca2+ channels
6. enhanced influx of Ca2+ into the presynaptic terminals INC transmitter release onto motor neurons during a sensory AP

Front 162

Describe how the hippocampus can act as a model for plasticity.

Back 162

identified as having long term synaptic plasticity, either undergoeing long-term potentiation or long-term depression, studied at the excitatory synapses here, important in memory formation and retrieval, shown to be activated during certain kinds of memory tasks and that damage here results in an inability to form certain types of new memories

Front 163

What is long-term potentiation (LTP)?

Back 163

long-lasting INC in synaptic strength

Front 164

What is long-term depression (LTD)?

Back 164

long-lasting DEC in synaptic strength

Front 165

What synaptic connections in the hippocampus show areas of LTP?

Back 165

dentate gyrus where the signal affects granules cells, from the granule cells to the CA3 pyramidal cells, and from the CA3 pyramidal cell to the CA1 pyramidal cells via Schaffer collaterals

Front 166

Describe long-term potentiation of Schaffer collateral-CA1 synapses.

Back 166

two stimulating eletrodes each activate separate populations of Schaffer collaterals providing test and control synaptic pathways, after a single stimuli either minutes before and one hour after a high freq. train of stimuli the high frequency stimulus train INC the size of the EPSP evoked by a single stimulus, if the pathway does not receive high frequency stimulation, the EPSP is unchanged

Front 167

Describe the time course of changes in the amplitude of the EPSPs evoked by stimulation of pathways.

Back 167

high frequency stimulation of pathway 1 causes a prolonged enhancement of the EPSPs in this pathway, this potentiation persists for several hours while the amplitude of EPSPs produced in 2 remain constant

Front 168

What happens when presynaptic and postsynaptic activity is paired?

Back 168

get LTP, single stimli applied to a Schaffer collateral synaptic input evokes EPSPs in the postsynaptic CA1 neuron, these stimuli alone do not elicit any change in synaptic strength, however when the CA1 neuron’s membrane potential is briefly depolarized in conjunction with the Schaffer collateral stimuli, there is a persistent INC in the EPSPs

Front 169

Describe the LTP at a CA1 pyramidal neuron receiving synaptic inputs from two independent sets of Schaffer collateral axons?

Back 169

strong activity initiates LTP at active synapses without initiating LTP at nearby inactive synapses, weak stimulation of pathway 2 alone does not trigger LTP, however when the same weak stimulus to pathway 2 is activated together with strong stimulation of pathway 1 both sets of synapses are strengthened

Front 170

What are the properties of LTP?

Back 170

1. it is state dependent-the state of the membrane potential of the postsynaptic cell determines whether or not LTP occurs
2. input specificity-LTP induced by activation of one synapse does not occur in other, inactive synapses that contact the same neuron, thus LTP is restricted to activated synapses rather than to all of the synapses on a given cell
3. associativity-weak stimulation of a pathway will not by itself trigger LTP, if one pathway is weakly activated at the same time that a neighboring pathway onto the same cell is strongly activated, both synaptic pathways undergo LTP

Front 171

What role does Mg block from NMDA receptors have on LTP?

Back 171

it is one mechanism of LTP, the NMDA receptor channel can open only during depolarization of the postsynaptic neuron form its normal resting level, depolarization expels Mg2+ from the NMDA channel, allowing current to flow into the postsynaptic cell, this leads to Ca2+ entry which in turn triggers LTP

Front 172

What effect do retrograde effects have on LTP?

Back 172

retrograde effects may be rleased from the postsynaptic neuron to go back to the presynaptic terminal and have an affect there, can include NO or BDNF

Front 173

Describe the signaling mechanisms underlying LTP.

Back 173

during glutamate release, the NMDA channel opens only if the postsynaptic cell is sufficiently depolarized, Ca2+ enters the cell through the channel (NMDA) and activates postsynaptic protein kinases, these postsynaptic kinases trigger a series of reactions that leads to insertion of new AMPA receptors into the postsynaptic spine, thereby INCing the cell’s sensitivity to glutamate (and entrance of Na+)

Front 174

Describe the mechanism responsible for long-lasting changes in synaptic transmission during LTP.

Back 174

the late component of LTP is due to PKA activating the transcriptional regulator CREB, which turns on expression of a number of genes that produce long-lasting changes in PKA activity and synapse structure

Front 175

Describe the mechanism of long-term synaptic depression in the cerebellum.

Back 175

glutamate released by parallel fibers activates both AMPA receptors and metabotropic glutamate receptors, the latter produces two second messengers (DAG and IP3) which interact with Ca2+ that enters when climbing fiber activity opens voltage-gated Ca2+ channels, this leads to activation of PKC which triggers clathrin-dependent internalization of postsynaptic AMPA receptors to weaken the parallel fiber synapse

Front 176

Describe the role of kinases and phosphatases in LTP and LTD.

Back 176

kinases affect LTP and phosphatases affect LTD

Front 177

What is required to maintain LTP?

Back 177

requires protein synthesis and formation of new synapses, repetitive high frequency stimulation induces LTP that persists for many hours, treatment with anisomycin (an inhibitor of protein synthesis), causes LTP to decay within a few hours after the high frequency stimulation

Front 178

What is epilepsy?

Back 178

recurrent seizures, a seizure is a sudden, synchronized excessive activation of a large number of neurons, seizure is a symptom of epilepsy, may be due to too much LTP

Front 179

What are the triggers for epilepsy?

Back 179

hypoxia, fever, light flashes, alcohol, loss of sleep, brain trauma, tumor

Front 180

How is epilepsy diagnosed?

Back 180

history, EEG and MRI

Front 181

How is epilepsy treated?

Back 181

medication (e.g. Phenobarbital), surgery (in extreme cases)

Front 182

What does the nissl stain do?

Back 182

stains RNA blue and is used to highlight important structural features of neurons, nissl substance appears dark blue due to the staining of ribosomal RNA giving the cytoplasm a mottled appearance

Front 183

How long does it take to regenerate nervous tissue?

Back 183

~3 months, also possible for the nervous tissue to not be repaired after several months

Front 184

What is Wallerian degeneration?

Back 184

the process by which the distal portion of a damaged axon segment degenerates, it is an active destructive process (not due to loss of energy), removal of myelin by Schwann cells, invasion of macrophages, denervated Schwann cells secrete NGF, divide and form bands of Bungner, all these events promote the Regeneration Process (prepare pathway for axonal regeneration)

Front 185

What types of cells are responsible for myelination?

Back 185

in the PNS, Schwann cells are, they myelinate only 1 neuron at a time, in the CNS, oligodendrocytes are and can myelinate multiple axons at one time

Front 186

What role do Schwann cells play in regeneration?

Back 186

they support regeneration, theyh produce a number of developmentally regulated molecules that promote axon growth and synapse formation, once macrophages clear debris from the degenerating peripheral stump the Schwann cells proliferate, express adhesion molecules on their surface and secrete neurotrophins and other growth-promoting signaling molecules, parent neurons release gene products that make receptors so they can react with Schwann cell factors

Front 187

What is necessary for successful regeneration?

Back 187

survival of cell body, axon growth and functional connection with target

Front 188

What are the trophic responses to injury for the different parts of the nervous system?

Back 188

1. CNS-INC in NGF and trkB
2. DRG-DEC p75, DEC trkA, INC trkB
3. distal nerve stump-INC NGF, INC BDNF, DEC NT-3, INC NT-4, INC p75, INC trkB, INC trkC
4. muscle-INC BDNF
5. skin-INC NGF

Front 189

What are some different trophic factors and where do they play a role in regeneration?

Back 189

1. NGF-DRGs, sympathetic ganglia
2. BDNF-motor neurons
3. CNTF-motro neurons
4. GDNF-motor neurons
5. FGF-retinal ganglion cells
6. IGF-sciatic nerve

Front 190

What is NGF?

Back 190

nerve growth factor, small secreted protein which induces the differentiation and survival of particular target neurons, critical for the survival and maintenance of sympathetic and sensory neurons, released from target cells, binds to and activates high affinity receptor (trkA) and is internalized into the neuron

Front 191

What is BDNF?

Back 191

brain-derived neurotrophic factor, protein that acts on certain neurons of the CNS and PNS that helps to suppor the survival of existing neurons and encourage the growth and differentiation of new neurons and synapses, active in hippocampus, allows for neural stem cells to make new neurons, binds to TrkB

Front 192

What is CNTF?

Back 192

ciliary neurotrophic factor, gene, promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations, survival factor for neurons and oligodendrocytes

Front 193

What is GDNF?

Back 193

glial cell line-derived neurotrophic factor, potently promotes the survival of many types of neurons, promotes the survival and differentiation of dopaminergic neurons and also prevents apoptosis of motor neurons induced by axotomy

Front 194

What is FGF?

Back 194

fibroblast growth factor, involved in wound healing

Front 195

What is nervus suralis?

Back 195

nervus suralis (sural nerve) acts as a substrate graft to bridge nerve segments, found on the posterior part of the leg, and on the lateral side of the foot and little toe

Front 196

Describe successful regeneration of motor nerve.

Back 196

if a nerve is cut and a muscle two muscles are denervated, during successful regeneration, only one motor nerve axon is reinnervated and innervates its muscle fiber, there is then a connection made between the 1st and 2nd muscle fiber, other nerve fiber is degenerated, the glia scaffold still remains

Front 197

What are the molecular and cellular responses that promote peripheral nerve regeneration?

Back 197

the Schwann cells is essential for this process, once the macrophages have cleared the debris from the degenerating peripheral stump the Schwann cells proliferate, express adhesion molecules on their surface and secrete neurotrophins and other growth promoting signaling molecules, in parallel, the parent neuron of the regenerating axon expresses genes that restore it to a growth state, the gene products are often receptors that allow the cell to respond to the factors provided by the Schwann cell

Front 198

Describe CNS axon degeneration.

Back 198

removal of debris is slow, growth cones hardly advance, astrocytes form scars

Front 199

What are some examples of attractive cues in the CNS?

Back 199

1. adhesive markers-laminin, fibronectin, cadherin, cell adhesion molecules (N-CAM, Ng-CAM)
2. diffusible markers-netrins, ephrins

Front 200

What are some examples of repellent cues in the CNS?

Back 200

1. adhesive markers-semaphorins, collapsing, myelin-associated protein
2. diffusible markers-semaphroins, netrins

Front 201

What is Nogo?

Back 201

is a membrane protein of oligodendrocytes, an inhibitor of neurite outgrowth specific to the CNS, blocking Nogo during neuronal damage (from diseases such as MS) will help to protect or restore the damaged neurons, possible treatment for auto-immune mediated demyleinating diseases and spinal cord injury regeneration

Front 202

What are the differences between the PNS and CNS that are important for regeneration?

Back 202

in the PNS, the Schwann cells in the distal nerve stump line up to form channels through which the axons can regrow, in the CNS, clearance of axonal debris and myelin is slow distal to the injury and astrocytes form a dense scar, the axonal growth in the injured CNS is limited to the site of the lesion

Front 203

What happens in regeneration in the CNS?

Back 203

in the absence of a glial scar, which are particularly prominent in long axon pathways in the brain, there is a series of local cellular changes at or near an injured site, these include the local degeneration of myelin as well as other cellular elements, the clearing of this debris by microglia that act as phagocytic cells in the CNS, and the local production of inhibitory factors by reactive astrocytes, oligodendroglia and microglia

Front 204

What supports CNS regeneration?

Back 204

PNS grafts, the growth promoting properties of peripheral nerve sheaths and Schwann cells facilitate growth of damaged axons within the CNS, severed axons from the optic nerve are apposed to a peripheral nerve graft, the axons now grow through the peripheral nerve graft to reach the superior colliculus a normal target for retinal ganglion cells, regenerated axons make synapses with targets in the superior colliculus

Front 205

What improves regeneration in the spinal cord?

Back 205

antibodies to myelin-associated proteins (such as Nogo) improve regeneration in the spinal cord

Front 206

What role does neurtrophin-3 have on regeneration?

Back 206

neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion, recovery from spinal cord injury can also be mediated by antibodies to neurite growth inhibitors

Front 207

How does Nogo inhibition enhance CNS regeneration?

Back 207

selectively expressed in oligodendroglial cells and is not found in Schwann cells, thorugh that blocking an inhibitory factor such as Nogo would lead to improved regeneration of long axon pathways in the CNS

Front 208

Describe the delivery of trophic factors.

Back 208

1. intracerebral/intraventricular infusion
2. slow-release implants
3. carrier-mediated transport across BBB
4. grafting of cells producing trophic factor
5. development of low-molecular weight agonists
6. fusion proteins with trafficking motifs for delivery along spinal/CNs

Front 209

What are some characteristics of spinal cord injury?

Back 209

1. compression, secondary hemorrhagic necrosis
2. large myelinated axons more affected
3. spill of ion contents (INC K+, DEC Na+, DEC Ca2+)
4. edema (- corticosteroids)
5. instability (immobilization and traction)
6. irreversible and reversible components
7. effects of hypothermia

Front 210

What are some statistics concerning spinal cord injury?

Back 210

8500 per year, 40% fatal (USA), caused by car accidents, falls, gun shot/stab wounds, diving, motor cycle

Front 211

What is the acute management for spinal cord injuries?

Back 211

immobilization, MRI, corticosteroids, gastric dilation, ileus, shock, infection

Front 212

What is the long-term management for spinal cord injuries?

Back 212

bladder and bowel functions, skin (decubitus ulcers), pulmonary, physiotherapy

Front 213

What is prospect for spinal cord injuries?

Back 213

10-20% will regain some modest functions

Front 214

What happens in optic nerve crush?

Back 214

loss of retinal ganglion cells, BDNF, GFDN, antibodies to myelin

Front 215

What happens in Parkinson’s?

Back 215

loss of substantia nigra neurons, BDNF, GDNF, fetal tissue transplant, stem cells

Front 216

What happens in Alzheimer’s?

Back 216

loss of cholinergic basal forebrain neurons, NGF, BDNF

Front 217

What happens in amyotrophic lateral sclerosis?

Back 217

loss of motorneurons, CNTF, BDNF, GDNF, IGF

Front 218

What is the primary mechanism for neuronal apoptosis after injury?

Back 218

apoptosis can be elicited by excitotoxicity via excess glutamagte, and by the binding of inflammatory cytokines to receptors in the neuronal membrane, in addition, loss of neuronal connections to a target and resultant deprivation of trophic support can initiate apoptosis, any or all of these stimuli, once present, result in the removal of the anti-apoptotic gene Bcl-2, cytochrome c is then released from mito, activatin caspacse-3 and obligating the cell to apoptotic death as caspase-3 stimulates destructive changes in downstream molecules

Front 219

What are some stimuli for apoptosis?

Back 219

DNA damage, hypoxia, stress, growth factor withdrawal

Front 220

What happens with blockage of Bcl-2?

Back 220

allows cytochrome c to be released by mito, cytochrome c leads to activation of caspase-9 and caspase-3

Front 221

What happens during apoptosis?

Back 221

chromosome condensation, DNA fragmentation, membrane blebbing, cytoskeletal changes

Front 222

What are some strategies to treat loss of specific neurons?

Back 222

1. drugs to enhance function of still remaining neurons (Parkinson’s: L-DOPA, Alzheimer’s-AChE inhibitors)
2. trophic factors to resuce remaining neurons
3. grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons
4. stem cells to replace lost neurons
5. prosthetic devices to replace function of lost neurons (pacemakers; cochlear implants)

Front 223

What are some drugs to enhance function of still remaining neurons?

Back 223

Parkinson’s: L-DOPA
Alzheimer’s: AChE inhbitors
those that are symptomatic, wears off as additional neurons degenerate, little benefit in advanced stages

Front 224

What effect does supplying trophic factors to rescue remaining neurons have?

Back 224

delivery problematic, side effects with systemic treatment, targeted delivery needed, supply of the trophic factor may not be the problem, but rather downstream problems with receptors or signal transduction

Front 225

Describe grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons.

Back 225

clinical results are too variable, in case of Parkinson’s outcomes are not better than deep brain stimulation, immunosuppressive treatment may be needed

Front 226

In mammals what are some examples of normal generation and replacement of neurons in the adult?

Back 226

olfactory receptor cells, taste receptor cells, interneurons in olfactory bulb, interneurons in hippocampus

Front 227

In other vertebrates what are some examples of normal generation and replacement of neurons in the adult?

Back 227

auditory and vestibular hair cells in birds, retinal cells (including retinal ganglion cells) in fish, song control neurons in forebrain of birds

Front 228

Describe the use of stem cells to replace lost neurons.

Back 228

risk of teratomas (engineer embryonic stem cells with regulatable suicide genes), will stem cell-derive dopaminergic neurons be more successful than primary dopaminergic neurons in fetal grafts?, immunosuppressive treatment needed?

Front 229

What do adult neural stem cells form?

Back 229

adult neural stem cells can be induced to form glial or neuronal phenotypes

Front 230

What is the mechanism for adult neural stem cell to glial or neuronal phenotypes?

Back 230

adult neural stem cell -> progenitor -> oligodendrocyte, astrocyte, immature neuron (-> maturation and integration to become mature neuron)

Front 231

Where are stem cells located?

Back 231

stem cells hide among ependymal cells in the subventricular zone, an ependymal cell undergoes asymmetric cell division to generate a subventricular zone progenitor cell, the progenitor cell undergoes several rounds of division to generate migratory neuronal precursor cells

Front 232

Describe the steps in neurogenesis in the adult mammalian brain.

Back 232

proliferation -> fate determination -> migration -> integration

Front 233

Where is stem cell therapy headed in the future?

Back 233

recent progress shows that neurons suitable for transplantation can be generated from stem cells in culture, and that the adult brain produces new neurons from its own stem cells in response to injury, these findings raise hope for the development of stem cell therapies in human neurodegenerative disorders, before clinical trials are initiated, we need to know much more about how to control stem cell proliferation and differentiation into specific phenotypes, induce their integration into existing neural and synaptic circuits and optimize functional recovery in animal models closely resembling the human disease

Front 234

What can improve hearing?

Back 234

1. cochlear implants
2. Atoh1 gene therapy-auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals

Front 235

Which forms of hearing loss are the most common?

Back 235

by far the most common forms of hearing loss involve the peripheral auditory system, namedly those structures that transmit and transducer sounds into neural impulses, monaural hearing deficits are the defining symptom of a peripheral hearing loss, can be conductive or sensorineural

Front 236

What is conductive peripheral hearing loss?

Back 236

involve damage to the outer or middle ear, can be due to occlusion of the ear canal by wax or foreign objects, rupture of the tympanic membrane, arthritic ossification of the middle ear bones

Front 237

What is sensorineural peripheral hearing loss?

Back 237

stems from damage to the inner ear, due to congenital or environmental insults that lead to hair cell death or damage to the auditory nerve

Front 238

How is conductive hearing loss treated?

Back 238

an external hearing aid is used to boost sounds to compensate for the reduced efficiency of the conductive apparatus, contain microphone, speaker and amplifier

Front 239

How is sensorineural peripheral hearing loss treated?

Back 239

if auditory nerve is intact can use cochlear implants to partially restore hearing, consists of a peripherally mounted microphone and digital signal processor that transforms a sound into its spectral components and additional electronics that use this information to activate different combinations of contacts on a threadlike multisite stimulating electrode array

Front 240

What else are cochlear implants good for?

Back 240

good for restoring hearing to people with hair cell damage, permitting them to engage in spoken communication

Front 241

What happens with damage to the phrenic nerve?

Back 241

breathing problems, if have damage to phrenic nerve there are breathing pacemaker systems available

Front 242

Describe MS plaques.

Back 242

MS in the medulla, have chronic inactive plaques that are seen in the center and right, whereas a shadow plaque is seen on the left above the inferior olive

Front 243

What is an example of loss of glial cells?

Back 243

MS, loss of oligodendrocytes, optic nerve, corticospinal tract, autoimmune disease, symptomatic treatment (corticosteroids)

Front 244

What are the emotional states?

Back 244

subjective experiences, visceral motor response, somatic motor responses, an emotional motor system

Front 245

Describe fear.

Back 245

it is a primary emotion experienced by all social animals and is an evolutionary need, it is a visceral motor and somatic motor response

Front 246

How is fear measured in animals?

Back 246

1. heart rate and BP
2. salivation
3. respiratory rate
4. scanning
5. startle
6. urination/defecation
7. freezing

Front 247

How is fear measured in humans?

Back 247

1. heart pounding or racing
2. dry mouth
3. pale skin
4. respiratory rate
5. hypervigilance
6. INC startle
7. urination/diarrhea
8. apprehensive expectation

Front 248

Describe the sympathetic component of fear.

Back 248

fight or flight, noradrenergic, postganglionic innervation includes the heart, salivary glands, airways, pupils, bladder and bowel

Front 249

Describe humor.

Back 249

it is a secondary emotion, it may be unique to humans and may have an evolutionary need, it is subjective, is a visceral and somatic motor response

Front 250

What are some other secondary emotions?

Back 250

pride, gratitude, shame

Front 251

Describe the parasympathetic division.

Back 251

for rest, digestion and enjoyment, cholinergic (Ach), postganglionic innervation includes the heart, salivary glands, airways, pupils, bladder and bowel

Front 252

Describe the emotional response to a visual stimulus.

Back 252

retina -> optic nerve -> occipital lobe -> visual association cortex -> then what?

Front 253

Describe the integration that occurs in the cortex.

Back 253

the emotional association structures, looks to see how a horror flick causes sympathetic activation and how a favorite song causes a sense of joy, also looks at what mediates external stimuli into subjective responses and physiologic responses

Front 254

What brain structures mediate emotion?

Back 254

hypothalamus, limbic system (including the limbic cortex and amygdale), brainstem

Front 255

What is the hypothalamus?

Back 255

a deep brain structure made up of a number of nuclei (under the thalamu), integral in emotional and sexual (and other) behaviors

Front 256

Where is the hypothalamus?

Back 256

base of the forebrain, behind the optic chiasm, forms part of the walls of the 3rd ventricle, contiguous with infundibular stalk to pituitary

Front 257

What does the hypothalamus do?

Back 257

integration of emotional response, forebrain, brain stem, spinal cord, sexual response and preferences, endocrine responses (neurosecretory, oxytocin, vasopressin directly to posterior pituitary

Front 258

How do we know that the hypothalamus integrates emotions and behavior?

Back 258

ablation studies, stimulation studies, primary emotions involved include fear and anger

Front 259

Describe ablation studies in cats.

Back 259

transaction through the midbran, disconnecting the hypothalamus and brainstem abolishes sham rage, the integrated emotional responses associated with sham rage survive removal of the cerebral hemispheres as long as the caudal hypothalamus remains intact (i.e. remove cerebral hemispheres get rage, remove hemispheres and hypothalamus then no rage)

Front 260

Describe stimulation studies on cats.

Back 260

lateral hypothalamic stimulation leads to rage and attack, other areas cause the cats to become defensive and fearful

Front 261

What is the route of information for the hypothalamus?

Back 261

input comes from the cortex (relatively unprocessed), output to brainstem’s reticular formation

Front 262

What is the reticular formation of the brainstem?

Back 262

is a brainstem web containing 100+ cell groups, controls sleep/awake cycle

Front 263

What is the route of information for the reticular formation (and other brainstem motor pools)?

Back 263

receives hypothalamic and cortical output (separate descending projections that run parallel to volitional motor system), output to somatic and autonomic effector systems (widespread visceral and somatic motor responses, affects cardiac, respiratory, bowels and bladder)

Front 264

What is the limbic system?

Back 264

link between higher cortical activity and the lower systems that control emotional behavior

Front 265

What are the contents of the limbic system?

Back 265

limbic lobe and deep lying structures including the amygdale, hippocampus, and mammilary bodies

Front 266

What is the limbic lobe?

Back 266

primitive cortical tissue, cingulated gyrus, parahippocampal gyrus

Front 267

Where is the limbic lobe?

Back 267

encircles the upper brain stem, around the corpus callosum

Front 268

What does the limbic system do?

Back 268

integrates information from cortical association areas, know this from experiments by Kluver and Bucy

Front 269

Describe Kluver and Bucy’s experiment.

Back 269

they removed the temporal lobe (destroying much of the limbic lobe) in the monkey, preoperation, the monkey was aggressive and had rage, post-op the monkey was docile, orally fixated, had INC sexual and compulsive behaviors, stimulate sympathetic NS stimulation

Front 270

What is Kluver-Bucy syndrome?

Back 270

in humans, is severe temporal lobe damage as seen in tumors, surgery or trauma, leads to visual agnosia (unable to recognize objects, although not blind), apathy, placidity, disturbance in sexual function, dementia, aphasia, amnesia

Front 271

What are some additional structures in the limbic system?

Back 271

orbital and medial prefrontal cortex, nucleus of thalamus, amygdala (nuclear mass) plus the limbic lobe

Front 272

Where is the amygdala?

Back 272

buried in the white matter of the temporal lobe, in front of the hippocampus

Front 273

What does the amygdala do?

Back 273

connects to the olfactory lobe, cerebral cortex (frontal and association areas of temporal lobe) and brainstem and hypothalamus, it is the emotional association area, links cortical areas that process sensory info to hypothalamus and brainstem effector systems, allows for emotional learning

Front 274

Describe the pathways in the rat brain that mediate the association of auditory and aversive somatic sensory stimuli.

Back 274

information processed by the auditory centers in the brainstem is relayed to the auditory cortex via the medial geniculate nucleus (1), the amygdale receives auditory information indirectly via the auditory cortex (2) and directly from one subdivision of the medial geniculate (3), the amygdale also receives sensory information about other sensory modalities, including pain (4), thus the amygdale is in a position to associate diverse sensory inputs leading to new behavioral and autonomic responses to stimuli that were previously devoid of emotional content (5)

Front 275

What role does the amygdala play in learned emotions?

Back 275

learned fear in rats via classical conditioning (associative learning, long term potentiation), abolish the fear response (infuse NMDA antagonist into amygdale during learning (no learning of fear) or remove one amygdale and block visual information from the eye on that side

Front 276

Describe learned fear.

Back 276

plays a possible role for amygdala in clinical disorders, in humans there are adaptive responses and non-adaptive responses (overreactive learned fear response, PTSD, phobias, gender differences)

Front 277

Describe the interaction between fear and the amygdala.

Back 277

conscious and unconscious, students shown images of fearful faces too quickly to register, amydala activity increased

Front 278

Describe the interaction between pleasure and the amygdala.

Back 278

emotional coloring of environments, INC recall when activated, learned rewards (anticipation of pleasure (or fear), drugs of abuse), emotional significance of environment (adapt/survive/reproduce)

Front 279

How does functional nueroimaging show up during craving?

Back 279

use PET and fMRI, activation of amygdala and anterior cingulated cortex, degree of cue activation correlated with craving severity, degree of activation correlated with likelihood of relapse (cocaine, alcohol, heroin, nicotine), as a result of intracellular changes, the previously cocaine addicted brain has persistently altered functioning (craving, drugs have a persistent effect)

Front 280

Describe the activation of brain sites for cocaine users and normal pleasures.

Back 280

cocaine abusers may experience a powerful urge to use when they encounter environmental cues associated with use, limbic regions of the brain are activated when watching cocaine related videos, activates the amygdala and anterior cingulate

Front 281

What happens with lesions to the amygdala?

Back 281

DEC learned rewards, DEC drug seeking behavior in animals (cocaine, heroin)

Front 282

what is the orbitofrontal cortex?

Back 282

posterior frontal lobe, mediates aggression and emotional responsiveness (damage to parts of frontal lobe: disinhibition, Phineas Gage), lesion input from amygdala DEC rage from disappointed primates

Front 283

What are some examples of structural clinical disorders?

Back 283

1. frontal lobe injuries
2. temporal lobe epilepsy (TLE)
3. amygdala abnormalities (Kluver-Bucy, Urbach-Wiethe)
4. rabies
5. lobotomy
6. stroke

Front 284

Who is Phineas Gage?

Back 284

was the foreman of a railway construction gang, on September 13 1848 as accidental explotion of a charge he had set blew his tamping iron through his head, the tamping iron was 3 feet 7 inches long and weighed 13.5 pounds, the tamping iron went in point first under his left cheek bone and completely out through the top of his head, landing about 25 to 30 yards behind him, he remained conscious and physically recovered

Front 285

Describe Gage before the accident.

Back 285

capable of efficient foreman, well-balanced, shrewd, smart businessman, sociable

Front 286

Describe Gage after the accident.

Back 286

fitful, disrespectful, profane, impatient and stubborn, unable to create and stick to future plans, his friends said he was no longer Gage

Front 287

Describe frontal lobe syndromes.

Back 287

impulse control, emotional incontinence, problems with planning, organization, motivation, rational decision making

Front 288

Describe the maturation of the brain.

Back 288

brain not adult until 20s

Front 289

Describe temporal lobe epilepsy.

Back 289

abnormal activity (seizure) of temporal lobe, olfactory/gustatory hallucinations, déjà vu/jamais vu, derealization/depersonalization, INC psychiatric disorders interictally, special EEG leads

Front 290

What are the symptoms of the Kluver Bucy Syndrome?

Back 290

agnosia, apathy, disturbed sexual behavior, dementia, aphasia, amnesia

Front 291

What are the causes of Kluver Bucy Syndrome?

Back 291

tumors, trauma, herpes, surgery

Front 292

What is Urbach-Wiethe?

Back 292

rare genetic disease, bilateral calcification and atrophy of anterior temporal lobes, unable to identify fear from photos

Front 293

What experiment shows that the amygdala is a key brain center for the experience of fear?

Back 293

patients with brain damage outside of the anterior-medial temporal lobe and damage to the amygdala were ask to rate the emotional content of a series of facial expressions, patients with damage to the amygdala recognized happiness, surprise, anger, disgust, sadness, and neutral qualities in facial expressions about as well as controls, however they failed to recognize fear

Front 294

What happens during rabies virus infection of the temporal lobes?

Back 294

anxiety/rage

Front 295

What happens during a lobotomy?

Back 295

separation of tracts from orbitofrontal cortex to amygdala

Front 296

Describe the lateralization of emotions.

Back 296

compare it to other lateralized brain functions (speech, attention (neglect syndromes)), left brain functions (number skills, written language, reasoning, spoken language, scientific, right hand), right brain functions (insight, 3-D forms, art, imagination, music awareness, left hand control)

Front 297

Describe the importance of the right hemisphere.

Back 297

expression and comprehension of emotional (affective) content, speech (prosody), images, L hemifield/L ear better at detecting emotional nuances of speech/images, L face may be more expressive of emotion, the understanding and expression of affective (mood) components to speech, relatively more L facial expression

Front 298

What happens with R hemisphere damage?

Back 298

(posterior frontal, right parietal), leads to aprosody, unable to read emotional coloring of speech, email (why we use emoticons such as :( and :), symbols to add prosody

Front 299

What happens with left hemisphere aphasia?

Back 299

poor comprehension of words, still understand emotional content, clinical situations

Front 300

What do the left and right hemisphere contribute to mood?

Back 300

L is for positive emotions (left lesions lead to a risk of depression), R is for negative emotions (R lesions may have elevated mood)

Front 301

What happens during a stroke?

Back 301

L anterior damage leads to depression, R anterior damage leads to euphoria, depression more than triples the likelihood of dying in the 10 years after a stroke, treatment with antidepressants may improve survival

Front 302

What is the limbic system?

Back 302

generates primitive emotional responses to situations, emotion allows for survival, allows to identify danger/threats (fear and aggression), allows to identify pleasure (natural rewards, eating, sex, social interaction)

Front 303

What is the reward pathway?

Back 303

specialized brain areas for producing and regulating pleasure (sex), includes the ventral tegmental area (VTA), nucleus accumbens (NA), prefrontal cortex, areas of limbic system (amygdala, hippocampus, hypothalamus), dopamine transmission

Front 304

What are some characteristics of the reward pathway?

Back 304

1. vulnerable
2. dysregulated when exposed to illicit drugs
3. normally adaptive goal directed behavior now directed to harmful substance

Front 305

What is the nucleus accumbens?

Back 305

it is the sweet spot for dopamine release in response to rewards

Front 306

How do dopamine levels change in nucleus accumbens when a patient reports feeling high?

Back 306

the higher a patient feels high the larger the change in dopamine levels

Front 307

What is the VTA and NA?

Back 307

primitive brain stem and limbic areas, activated by drugs of abuse, activation of these primitive areas can override more evolved cortical areas, drugs activate the pathway with force and persistence not seen with natural rewards

Front 308

What do drugs of abuse do to neurotransmission of emotions?

Back 308

disrupts it, synthetically produce feelings of pleasure in the reward system by altering neurotransmission of dopamine neurons, variety of sites and receptors where drugs affect transmission, all substances have a common endpoint

Front 309

Describe synaptic transmission.

Back 309

after binding, neurotransmitters release from receptor and goes back into the cleft, removed by enzymes or reuptake pump/transporter back into terminal, quick removal of transmitters allow for precise communication between neurons

Front 310

What happens with stimulation of brain reward areas?

Back 310

direct electrical stimulation of brain reward areas will lead to elevated dopamine, stimulates natural rewards

Front 311

What effect does sex and food have on dopamine levels?

Back 311

important for evolution, linking pleasurable feelings to food and sex is important in continuing the species

Front 312

What do differenet drugs do to different levels of transmitters?

Back 312

1. amphetamines INC DA levels 1000%
2. cocaine INC DA levels 350%
3. nicotine INC accumbens activity 225%

Front 313

What is the definition of addiction?

Back 313

addiction is a disease of brain reward centers that ensures the survival of organisms and species

Front 314

What are drug effects on neurotransmission?

Back 314

alcohol, heroin, nicotine excite the dopamine neurons in the VTA to INC dopamine release, stimulants can stimulate dopamine dumping and block reuptake

Front 315

Describe the relationship between drug abuse and addiction.

Back 315

drug abuse is initially voluntary behavior, drug addiction is compulsive drug abuse in the presence of adverse consequences, drug use and addiction are associated with long term physical functional changes in the brain, addiction is influenced by social, genetic and behavioral factors

Front 316

What are drug’s effects on the cell?

Back 316

drugs of abuse all directly or indirectly INC dopamine binding to postsynaptic receptor with acute behavioral effects, chronically, this INC cAMP levels and leads to a cascade of changed cell activity, activation of transcription factor CREB and changes in gene expression (changes in synapses, cell structure and function), the resulting intracellular changes appear to be the molecular and cellular basis of addiction (persistent behavioral abnormalities)

Front 317

What effect do drugs have on learning?

Back 317

intracellular changes for addiction similar to learning, both activities share intracellular signaling cascades (cAMP) and depend on activity of CREB, INC neuronal capacity for excitatory inputs, another transcription factor-delta fosB

Front 318

Describe the relationship between learning and addiction.

Back 318

learning and addiction show similar changes in neuron morphology, similar changes at the level of the synapse, multiple similar changes in the neuron, long term changes, addiction is long term, phasic dopamine release signals prediction of reward, gambling

Front 319

What is tolerance?

Back 319

needing INC doses of drug to achieve same response, body more efficient in clearing drug, cells more resistant to drug effect, receptor down regulation or DEC efficiency with activating cAMP

Front 320

What is craving?

Back 320

intense desire, can occur even after initial use, single dose of cocaine in rats can INC glutamate transmission for 5 days (back to baseline in 10 days)

Front 321

What happens with cocainie addicted brains?

Back 321

as a result of intracellular changes the previously cocaine addicted brain has persistently altered functioning (ie craving), amygdala (again)

Front 322

Describe chronic drug effects.

Back 322

over time, brain activity, as measured by PET, trends towards normal, neurophysiological function may never normalize

Front 323

What is the effect of drug use on descision making?

Back 323

studied using the Iowa gambling task, compare with patients with brain damage (ventromedial prefrontal cortex), 63% of addicts as impaired as brain damaged patients (some variability), impaired decision making, unable to learn from recent feedback

Front 324

What is the Bechara gambling task?

Back 324

patients are presented with four decks of cards, they select from different card decks to receive imaginary rewards and penalties, unknown to the patient, some of these decks give good rewards, but occasionally dole out hefty penalties, in contrast, the good decks give moderate rewards and only small penalties, normal subjects soon stop selecting cards from bad decks but orbitofrontal patients do not stop

Front 325

What are the correlates for the Iowa gambling task?

Back 325

oblivious to future positive or negative consequences, guided by immediate prospects

Front 326

What are some different drugs that impair decision making?

Back 326

alcohol, cannabis, cocaine, opiod, methamphetamine, meth may be more harmful than others, some substance users will not have impaired decision making

Front 327

What are the take homes for the emotion lecture?

Back 327

drug addiction happens at a cellular level, permanent brain changes include craving, deficits in memory, mood, stimulants are key offenders

Front 328

What is the take home message on depression?

Back 328

severe depressed mood and impaired functioning, #2 among disabling disease of Westernized countries, 15% lifetime risk of completed suicide, Nevada ranks 1 to 4 rate in the country, Nevada rate for elderly suicide is 300% of national average, strong genetic component, can be neurotransmitter, structural or functional problem

Front 329

How is depression diagnosed?

Back 329

need 5 or more symptoms of 2+ weeks
1. depressed mood
2. DEC energy
3. sleep and appetite changes
4. memory/concentration changes
5. thoughts of death/suicide
6. guilt
7. DEC interests
8. tearfulness

Front 330

What is the role of depression on the amygdala?

Back 330

INC blood flow in depression, asymmetry R amygdala gets more, correlates with severity of depression

Front 331

What is the role of the left prefrontal cortex on depression?

Back 331

depression as a power failure of L PFC, moderates negative emotional output of amygdala (dread, fear, sadness, stroke patients, DEC blood flow on PET scans of depressed (non-stroke) patients, activity normalizes with medication treatment

Front 332

What happens with asymmetries in PFC function?

Back 332

peppy L PFC (extraversion), levels of corticsol are lower, less reactive to stressors, individual differences measured in infants, adults

Front 333

Describe the left prefrontal cortex in depressed patients.

Back 333

smaller volume of ventral anterior cingulated in depressed patients (40% smaller) on PET scans with less blood flow, blood flow normalizes with treatment of depression, smaller volume may be related to loss of glial cells (cell loss from toxic cortisol levels secondary to stress)

Front 334

Describe the role of the hippocampus on depression.

Back 334

animals experiencing repeat stress (shrinking of hippocampus), hippocampus may shrink in people with recurrent depression, hippocampal cell loss may lead to cognitive decline, atrophy of neurons with chronic exposure to stress and cortisol, death of neurons with severe and prolonged stress, neuroendangerment with moderate levels of stress/cortisol

Front 335

Why are some individuals more vulnerable to depression?

Back 335

stress/loss, genetic traits

Front 336

What role does stress play on the body?

Back 336

stress plays a role in inflammation (IL, cytokines), stress DEC BDNF in hippocampus (could contribute to atrophy and DEC functioning of neurons)

Front 337

What is the summary on emotion lecture?

Back 337

1. emotional responses mediated by hypothalamus and limbic structures
2. injuries to different areas lead to disturbed behaviors and emotions
3. addiction is a brain disease
4. depression is a brain disease (environment contributes, strong genetic component, treatment: neurotransmitter manipulation)

Front 338

What is sexual dimorphism?

Back 338

two forms, have different behaviors, anatomy, hormones and physiology

Front 339

What are sexual dimorphic behaviors?

Back 339

in animals includes sexual behaviors and rearing of young, in humans includes sexual affiliation, spatial thinking, use of language and what is attractive in a mate

Front 340

Describe sexual behaviors.

Back 340

all behaviors are based on underlying neuronal circuitry

Front 341

Describe anatomical differences in sexual dimorphics.

Back 341

brain differences (in rodents two distinct forms, in humans there is a continuum), reflects behavioral differences as well

Front 342

What is the genotypic definiation of sex?

Back 342

XX female, XY male, XXY (rare), XO (rare), unchangeable

Front 343

What is Turner’s Syndrome?

Back 343

XO, short stature, low hairline, shield-shaped thorax, widely spaced nipples, shortened metacarpal IV, small finger nails, brown spots (nevi), characteristic facial features, fold of skin, constriction of aorta, poor breast development, elbow deformity, rudimentary ovaries, gonadal streak (underdeveloped gonadal structures), no menstruation

Front 344

What is the phenotypic definition of sex?

Back 344

internal and external genitalia, XX (have ovaries, uterus, vagina, labia), XY (testes, seminal vesicles, penis and scrotum), this is modifiable

Front 345

What is gender identification?

Back 345

subjective perception of one’s sex (fixed age 3 or 4), confusing for some, societal expectation, sexual orientation (social construct-homosexualitey diagnosed and treated 50 years ago), divergence in how brain vs. body are masculinized

Front 346

What influence does hormones have on dimorphism?

Back 346

1. genotypes-> gonads
2. gonads -> sex hormones
3. sex hormones -> developmental effects on the brain
4. fetuses sexually bipotential in early weeks

Front 347

What role does the hypothalamus have on sex?

Back 347

mediates sexual behaviors, multiple factors (arousal, vascular and smooth muscle control, hormones), ablate parts of the hypothalamus (preoptic area) and male rats will lose copulatory behaviors

Front 348

In females, what role does the hypothalamus have on sex?

Back 348

1. estrous cycle-most animals (seasonal mating), some species have males cycle with day length
2. menstrual cycle-hidden estrous, sexual behavior only partially influenced by cycle/hormonal states
3. GnRH-LH, FSH from anterior pituitary

Front 349

What hormones are secreted by the hypothalamus?

Back 349

anterior pituitary releases FSH and LH, testes (testosterone and sperm production) and ovaries (estrogen secretion, ovulation) feedback to the brain

Front 350

What hormones are released from the anterior pituitary?

Back 350

ACTH, TSH, prolactin, GH, FSH, LH

Front 351

What hormones are released form the posterior pituitary?

Back 351

oxytocin, vasopressin (anti-diuretic hormone ADH)

Front 352

In males, what role does the hypothalamus have on sex?

Back 352

parallel feedback loops on hormones (GnRH-cyclical release LH/FSH), nonseasonal sexual behaviors, sexual activity limited by female receptivity

Front 353

What happens with hypothalamic dysfunction?

Back 353

1. Kleine Levin Syndrome
2. Periodic hypersomnolence
3. periodic hypersexuality
4. also appetite, mood and memory changes, may respond to lithium treatment

Front 354

What effect do sex hormones have on the brain?

Back 354

testosterone to female rat pups (reduction of synapses in hypothalamus region, brain became more male), castrating male rat pups (INC synapses in region, brains more female, behavior more female (lordosis), reversed if add testosterone to castrated male rat pups

Front 355

What is the sexually dimorphic nucleus (SDN)?

Back 355

nucleus in rodent hypothalamus, different size in males than females, development under influence of hormones

Front 356

What do hormones do to the fetal brain?

Back 356

organize it, testosterone -> estradiol in male brain, estrogen -> estradiol in female brain, timing of midgestational hormonal surges key to establishment of sex differences in fetal brain, testosterone also acts on androgen receptors

Front 357

In development, when is there a fetal testosterone surge?

Back 357

weeks 7-22

Front 358

What is alpha-fetoprotein?

Back 358

binds circulating materal estrogens but not testosterone, prevent fetal brains from early exposure to maternal estrogens, in fetal circulation and CSF (screen for neural tube defects, Down’s syndrome)

Front 359

Describe brain masculinization.

Back 359

default is female, timing of testosterone surge important for adequate number and type of receptors, too soon and inadequate receptor sites, TDF gene on Y chromosome signals testosterone secretion, need aromatase to convert testosterone to estradiol

Front 360

Describe body masculinization.

Back 360

default is female, testosterone converted to DHT, binds to peripheral androgen receptors

Front 361

Describe the mechanism of brain and body masculinization.

Back 361

both the brain and body of mammals are initially organized according to a female characteristic plan, maleness emerges from two distinct influences of testosterone on body tissues, masculinization of the brain mediated by estrogen and of the body by dihydrotestosterone (DHT), different tissues can convert testosterone to different products because of the enzyme they contain, DHT is manufactured in cells containing 5-alpha-reductase, and E is manufactured in those that contain aromatase

Front 362

Describe the binding of hormones in rat brain.

Back 362

hormone freely diffuse into cells, receptors and binding proteins in cytoplasm, distributions of receptor types, rat brain estradiol receptors (hypothalamus, amygdala)

Front 363

Describe the estrogen receptor.

Back 363

binds estradiol, transcriptional factor activates gene transcription, sexually dimorphic neural circuits, estrogen binds to estrogen receptor/transcription factor, this then binds to DNA and promotes or inhibits transcription

Front 364

What are the types of brain changes via hormone binding?

Back 364

neuronal size, dendritic length and spine density, branching, number of synapses

Front 365

Describe estrogen as a growth factor.

Back 365

fetal and adult brains, brain changes can be cyclical (with hormonal/estrous cycles), pregnancy and delivery, hypothalamus/hippocampus, substance response can depend on menstrual phase, PMS (cyclical effects of hormone on limbic system)

Front 366

Describe the relationship between CNS dimorphisms and sexual functioning.

Back 366

spinal nucleus of the bulbocavernosus (rodents), Onuf’s nucleus in sacral spinal cord (humans), smaller muscle in females, fewer neurons in females

Front 367

What role does the hypothalamus have on structural dimorphisms?

Back 367

in rodents and monkeys, sexually dimorphic nucleus of preoptic area, high level of neuronal firing in males during specific phases of copulation, lesions (abnormal sexual behaviors, DEC sexual response, abnormal mate selection), in humans, interstitial nuclei of anterior hypothalamus (INAH)

Front 368

Describe the interstitial nuclei anterior hypothalamus (INAH).

Back 368

4 nuclei, dimorphic at different developmental stages (2X larger in males, N1 same size in females until age 2, N1 DEC in size after age 50 both gender, changes related to sex hormones)

Front 369

What is the corpus callosum?

Back 369

fiber bundle connecting hemispheres (female brains less lateralized/more cross hemispheric communications), different shape to the splenium (more bulbous in women, unclear significance)

Front 370

What structures are larger in healthy male brains relative to cerebrum size?

Back 370

orbitofrontal cortex, amygdala, corpus callosum

Front 371

What structures are larger in healthy female brains relative to cerebrum size?

Back 371

cingulated gyrus, occipital lobe

Front 372

What are some structural dimorphisms?

Back 372

apoptosis, trophic factors (size differentiation)

Front 373

What are some functional dimorphisms?

Back 373

lactation, parenting, language, anxiety, depression, paraventricular nucleus and the supraoptic nucleus are the same size and shape, female nuclei sensitive to postpartum hormonal surges, formation of gap junctions (oxytocin surges), mediate lactation

Front 374

Describe the difference in cognitive function between males and females concerning brain dimorphisms.

Back 374

language, in F, more aphasia if L anterior damage (less aphasia in general), in M, more aphasia if L posterior damage

Front 375

Describe the development of lateralization.

Back 375

boys lateralize visuospatial info age 6, girls lateralize at 13, effects of circulating hormones, amygdala activated more than in females (R for male and L for female)

Front 376

Describe the relationship between the brain and sexual orientation.

Back 376

differences among one gender that may be related to straight/gay, brain structures (hypothalamic nuclei) through to differ in gay/straight male brains do not appear to reliably correlate, fMRI suggest male and lesbian brains may share response to hormone activation on the hypothalamus

Front 377

What is some other evidenece for the biology of homosexuality?

Back 377

nonhumans, genetics, this is a highly politicized area of research, must be cautious in reviewing agenda, methods, analysis and interpretation

Front 378

What is some nonhuman homosexual behavior?

Back 378

fruit flies (some males court other males), marine birds (some females pair off to raise chick)

Front 379

Describe homosexuality in sheep.

Back 379

a hypothalamic nucleus is smaller in male sheep that prefer to mount other rams, the volume of a sexually dimorphic nucleus in the ovine medial preoptic area/anterior hypothalamus varies with sexual partner preference, over 200 species

Front 380

Describe the genetics of homosexuality.

Back 380

variable research findings, 30% concordance in MZ twins, 0-22% in DZ twins

Front 381

Describe the rearing effects of homosexuality.

Back 381

children raised by one or two homosexuals (no difference in sexual orientation, psych illnesses, IQ or moral attitudes, INC tolerance to diversity, discussions about sex, less likely to be abused sexually or physically)

Front 382

Describe the relationship between maternal exposures and homosexuality.

Back 382

femal fetuses exposed to diethylstilbestrol (saturates alpha-fetoprotein, more tomboy behavior), female fetuses with adrenogenital syndrome (high levels of circulating androgens in utero, not bounded by AFP, fetal brain exposed, children with male play behavior, INC homosexuality (up to 40%)

Front 383

Describe the relationship between maternal stress and homosexuality.

Back 383

female rats exposed to stress during third week of gestation, INC sexual ambiguity in male offspring (normal 80% males are studs, 20% duds (asexual), stressed 20% studs, 60% bisexual, 20% duds, ratios can be altered by social rearing conditions, change in stressed mothers: peak testosterone too early)

Front 384

Describe the relationship between maternal factors and homosexuality.

Back 384

androgen production may be DEC in stressed or ill women, fetal androgen production may be premature relative to receptor status, male sibling birth order, boys born to wartime mothers: higher rates of homosexuality, what social factors also play a role

Front 385

Describe maternal stress.

Back 385

dud males more nurturing of rat pups, female offspring of stressed mothers less interested and able to care for young

Front 386

Give a summary concerning brain structure and human sexuality.

Back 386

1. small differences in brain structure: large differences in sexual behaviors
2. brain dimorphisms result form effects of circulating hormones during development
3. discrepancies: timing of hormone surges, size of M vs. F vs. homosexual not consistent

Front 387

What does testosterone contribute too?

Back 387

contributes to male and female sexuality, male levels peak teens-20s, improve libido

Front 388

Describe the neurochemical activation of adult sexuality in males.

Back 388

arginine vasopressin (AVP), in amygdala and hypothalamus, mediates both aggressive and sexual drives (extra AVP: more territorial and combative (sexual jealousy), released from pitutitary during anticipatory sexual behavior)

Front 389

Describe the neurochemical activation of adult sexuality in females.

Back 389

oxytocin, manufacture is under control of estrogen, if released into male circulation: orgasm, in females: more relevant to courting and copulation (peripherally critical for birth and nursing), block oxytocin in female rats: no sexual receptivity, mediates sexual pleasure in females, women who breast feed

Front 390

Describe the neurochemical mediaion of sexual pleasure.

Back 390

dopamine and opioids implicated in reward system, opiate blockade more effective in DECing sexual reward in males, opiate addicts: “orgasmic rush” (dopamine, nucleus accumbens)

Front 391

Describe intersexuality.

Back 391

1-2% of live births, chromosomal abnormalities, testicular feminization, 5 alpha reductase deficiency, congenital adrenal hyperplasia, hermaphrodism

Front 392

Describe Kleinfelter’s syndrome.

Back 392

XXY, small gonads, passive, possibly developmentally slow or delayed, can also be XYY (lower IQ, tall), tall stature, slightly feminized physique, tendency to lose chest hairs, female-type pubic pattern, testicular atrophy, osteoporosis, breast development, poor beard growth, frontal baldness absent

Front 393

Describe testicular feminization (androgen insensitivity syndrome).

Back 393

defective gene fro androgen receptor, internal genitalia Male, external genitalia Female (or ambiguous), XY gender ID = female, amenorrhea (Joan of Arc)

Front 394

Describe 5 alpha reductase deficiency.

Back 394

“testes at twelve”, Dominican Republic, 5 alpha reductase: converts testosterone and allows for external male genitalia, born female, at puberty: testicular secretion of androgens INC and male genitalia develop

Front 395

Describe congenital adrenal hyperplasia.

Back 395

females with overactive adrenals during development (ambiguous genitalia), high levels of circulating androgens, tomboys as children, later choice of female sexual partner

Front 396

Describe hermaphrodism.

Back 396

both testis and ovary present (ovotestis), spectrum of external genitalia, XX, XY or mosaic, rare

Front 397

Are there brain differences in transsexuals?

Back 397

bed nucleus of the stria terminalis, smaller in women than men, transsexuals: smaller than in women

Front 398

In conclusion, what determines gender?

Back 398

genes, X, Y, synchronization of hormonal surges, effects of enzymes and intact receptor systems, mismatches between brain and body development are possible

Front 399

Describe the neurophysiology of bonding.

Back 399

evolutionary adaptive, secure base associated with optimal personality development, chronic insecurity-developmentally impaired adults (trust, intimacy)

Front 400

What are nurturant brain circuits?

Back 400

more developed in women than men, probably evolved from subcortical systems that involve female sexual urges, pituitary hormones: oxytocin (uterine contractions, lactation, sexual feelings, proliferation of receptors in the brain in response to estrogen levels (stria terminalis)

Front 401

What does oxytocin do for maternal feelings and behaviors?

Back 401

nesting, other behaviors, damage to this structure signifantly impairs maternal behavior

Front 402

What role does oxytocin have on maternal behaviors in rats?

Back 402

virgin females exhibit maternal behavior with direct oxytocin administration (nest building, retrieving, attempts to nurse), maternal behaviors following first delivery can be blocked by oxytocin antagonists (not true of later deliveries (learned behavior), presence of estrogen and prolactin enhances oxytocin response, maternal behavior can also be learned (modeling)

Front 403

What role does oxytocin have on maternal behaviors in humans?

Back 403

released in nursing mothers, causes the suckling reflex (conditions to various infant stimuli), directly activates brain reward processes (dopamine and opiods), blocks tolerance to opiod reward (sustains high affective arousal in brain’s opioid experiences

Front 404

What are the implications?

Back 404

baby to the brest right after delivary, nursing reinforces the social bond between mother and child via oxytocin and opioids (short and long term)

Front 405

What are some other benefits of breast feeding?

Back 405

immune system, IQ, protective effects for infant (leukemias, obesity and diabetes, schizophrenia), protective effects for mother (breast cancer, post partum depression)

Front 406

Describe learned behavior.

Back 406

nurturance can be modeled and learned, adoptive parents can bond, some adoptive mothers can lactate

Front 407

Describe social bond.

Back 407

positive social interactions derive part of their pleasure form endogenous opioid release (play in young, grooming in adults), understanding of opioid addiction and related behaviors

Front 408

More on social bond.

Back 408

1. animals prefer to spend more time with animals in whose present they experienced high brain oxytocin and opioid activites
2. primitive emotional reason we choose to be with friends/family vs. strangers
3. friendships cemented by same chemical systems that mediate maternal and sexual urges
4. understanding behaviors related to drug addiction

Front 409

Give a summary for the sexuality lecture.

Back 409

1. default female phenotype, fetal hormonal exposure for male genotype
2. deep brain structures mediate sexual behaviors
3. vasopressin/oxytocin integral
4. nurturant and social bonding appear to have evolved from older sexual circuitry

Front 410

How is CN I tested?

Back 410

test ability to identify familiar aromatic odors, one naris at a time with eyes closed, scratch n sniff test, whole cloves or peppermint, don’t use noxious odors (kerosene), elicits pain fibers

Front 411

How is CN II tested?

Back 411

test vision with Snellen chart and Rosenbaum near vision chart, ophthalmoscopic exam, look at optic disk, visual acuity, color vision, visual fields to confrontation, papillary response (miosis-pupil gets smaller, mydriasis-when pupil gets really large), direct response, consensual response, accommodation, convergence movements, optokinetic nystagmus (allows the eye to follow objects in motion with the head still)

Front 412

How is CN III tested?

Back 412

test visual fields by confrontation and extinction of vision, test extraocular eye movements

Front 413

What is diplopia?

Back 413

double vision

Front 414

How is CN IV tested?

Back 414

inspect eyelids for drooping, test extraocular eye movements

Front 415

How is CN VI tested?

Back 415

inspect pupils’ size fore equality and their direct and consensual response to light and accommodation, test extraocular eye movements

Front 416

How is CN V tested?

Back 416

inspect face for muscle atrophy and tremors, palpate jaw muscles for tone and strength when patient clenches teeth, test superficial pain and touch sensation in each branch (test temperature sensation if there are unexpected findings to pain or touch)

Front 417

How is CN VII tested?

Back 417

inspect symmetry of facial features with various expressions, test ability to identify sweet and salty tastes on each side of the tongue

Front 418

How is CN VIII tested?

Back 418

test sense of hearing with whisper screening tests or by audiometry, compare bone and air conduction of sound, test for lateralization of sound

Front 419

How is CN IX tested?

Back 419

test ability to identify sour and bitter tastes, test gag reflex and ability to swallow

Front 420

How is CN X tested?

Back 420

inspect palate and uvula for symmetry with speech sounds and gag reflex, observe for swallowing difficulty, evaluate quality of guttural speech sounds (presence of nasal or hoarse quality of voice)

Front 421

How is CN XI tested?

Back 421

test trapezius muscle strength (shrug shoulders against resistance), test sternocleidomastoid muscles strength (turn head to each side against resistance)

Front 422

How is CN XII tested?

Back 422

inspect tongue in mouth and while protruded for symmetry, tremors and atrophy, inspect tongue movement toward nose and chin, test tongue strength with index finger when tongue is pressed against cheek, evaluate quality of lingual speech sounds

Front 423

When checking Cn V, VII, IX, X and XII what is the difference between dysarthria and Broca’s aphasia?

Back 423

dysarthria is a production problem, can’t move tongue or throat to make words, Borca’s aphasia is a brain problem, can’t think of word but can say words (words make no sense but can make words out), stroke common cause for both, myasthenia also can cause dysarthria

Front 424

What makes up the motor exam portion of the neurological exam?

Back 424

1. observation-involuntary movements, tremor, hypokinesia
2. inspection-muscle wasting, fasciculations
3. palpation-tenderness (myositis), fasciculations
4. muscle tone-hyporeflexia, hyperreflexia
5. functional testing-drift, fine finger movements, rapid toe tapping
6. strength of individual muscle groups

Front 425

What is hypokinesia?

Back 425

slow or diminished movement of body musculature, associated with basal ganglia diseases, 4 types include bradykinesia (slowness of movement), freezing (can’t move), rigidity (INC in muscle tension when moved by an outside force), postural instability (loss of ability to maintain an upright posture)

Front 426

What are fasciculations?

Back 426

a muscle twitch, a small, local, involuntary muscle contraction visible under the skin arising from the spontaneous discharge of a bundle of skeletal muscle fibers, associated with lower motor neuron pathology

Front 427

What is myositis?

Back 427

inflammation of the muscles, considered likely to be caused by autoimmune conditions, rather than directly due to infection, see an elevation of creatine kinase

Front 428

What is hyporeflexia? hyperreflexia?

Back 428

1. hyporeflexia-presence of below normal or absent reflexes, generally associated with a lower motor neuron deficit
2. hyperreflexia-overactive or overresponsive reflexes, include twitching or spastic tendencies, indicative of upper motor neuron disease

Front 429

What makes up the reflex portion of the neurological examination?

Back 429

1. deep tendon reflexes-compare both sides, reinforcement, clonus
2. plantar response-babinski’s sign
3. reflexes tested in special situations-suspected spinal cord damage, frontal release signs, posturing
4. frontal lobe release-snout, grasp, palmomental

Front 430

What is clonus?

Back 430

is a series of involuntary muscular contractions due to sudden stretching of the muscle, sign of certain neurological conditions, associated with upper motor neuron lesions, rapidly dorsiflex the ankle

Front 431

What is Babinski’s sign?

Back 431

identifies disease of the spinal cord and brain, exists as a primitive reflex in infants, check lateral side of the sole of the foot by running from heel to the metatarsal pads, if toes curve inward and the foot everts this is normal, if toes fan out the Babinski sign is + indicating damage to the CNS, can indicate UMN damage to the spinal cord in the thoracic or lumbar region, or damage to the corticospinal tract

Front 432

What makes up the coordination and gait portion of the neurological examination?

Back 432

1. appendicular coordination-rapid alternating movements (dysdiadochokinesis), finger-nose-finger test, heel-shin test, ataxia, overshoot
2. Romber test
3. gait-ordinary gait, tandem gait, special gait testing

Front 433

What is Dysdiadochokinesis?

Back 433

the inability to perform rapid, alternating movements, feature of cerebellar ataxia, and is the result of lesions to the posterior lobe of the cerebellum, thought to be caused by the inability to switch on and switch off antagonizing muscle groups

Front 434

What is the Romberg test?

Back 434

used to asses the dorsal columns of the spinal cord which are essential for joint position sense (proprioception), if + suggests that ataxia is sensory in nature, ask person to stand erect with feet together and eyes closed and watch their movements, + if swaying

Front 435

hat makes up the sensory exam of the neurological examination?

Back 435

1. primary sensation-asymmetry, sensory level, pain (sharp vs. dull), temperature (cold vs. warm), vibration sense (tuning fork), joint position sense, light touch and two-point discrimination
2. cortical sensation-graphesthesia, sterognosis (identify objects by touch)
3. extinction, hemineglect (lesion of right parietal lobe)
4. dermatomes, myotomes, sclerotomes

Front 436

What is graphesthesia?

Back 436

ability to recognize writing on the skin purely by the sensation of touch, tested in order to test for certain neurological conditions

Front 437

What is stereognosis?

Back 437

ability to perceive the form of an object by using the sense of touch, this sense along with tactile spatial acuity, vibration perception, texture discrimination and proprioception are mediated by the dorsal column-medial lemniscal system of the CNS

Front 438

What is hemineglect?

Back 438

is a neurological condition in which after damage to one hemisphere of the brain, a deficit in attention to the opposite side of space is observed, most commonly on right cerebral side, if affect right parietal lobe can lead to neglect for the left side of the visual field causing a patient with neglect to behave as if the left side of sensory space is nonexistent, can still turn left

Front 439

What makes up the coma exam of the neurological examination?

Back 439

1. level of consciousness
2. ophthalmoscopic exam
3. vision (blink-to-threat)
4. papillary responses
5. vestibule-ocular reflex
6. corneal reflex
7. gag reflex
8. withdrawal from painful stimulus
9. posturing reflexes

Front 440

What is scotoma?

Back 440

is an area or island of loss or impairment of visual acuity surrounded by a field of normal or relatively well-preserved vision, blind spot is a scotoma, caused by demyelinating disease such as MS

Front 441

What is the oculocephalic reflex?

Back 441

medical sign seen in comatose patients in which the eyes will move opposite the direction the head is turned, thus maintaining a more-or-less steady gase, determines if a comatose patient has intact function of the brainstem, normally in a conscious person this reflex is suppressed by the cerebral cortex

Front 442

What happens during an upper motor neuron lesion vs. a lower motor neuron lesion in the face?

Back 442

UMN lesion leads to weakness of inferior facial muscles, LMN lesion leads to weakness of superior and inferior facial muscles

Front 443

What is decorticate?

Back 443

posture position, decorticate (flexor, present with arms flexed or bent inward on the chest, hands are in fist and legs extended caused by disinhibition of the lateral vestibulospinal tract and red nucleus, facilitates motor neurons in the lower cord serving extensor muscles of the lower extremities)

Front 444

What is decerbrate?

Back 444

decerbrate (involuntary extending of the upper extremities in response to external stimuli, head is arched back, arms are extended by tehs ides and legs are extended, extended elbows, caused by damage to brain stem below the level of the red nucleus)

Front 445

Compare LMN and UMN defects.

Back 445

1. strength-DEC, DEC
2. muscle tonus-flaccid, spastic
3. atrophy-present, disuse/less
4. reflexes-DEC, INC
5. plantars-flexor, extensor
6. fasciculations-present, absent

Front 446

What is spasticity?

Back 446

INC resistance to passive movement with sudden collapse (clasped knife collapse, UMN sign), pyramidal sign

Front 447

What is rigidity?

Back 447

cogwheel and plastic tonus, paratonia (basal ganglion signs), extrapyramidal sign

Front 448

What is monoparesis?

Back 448

UMN lesion but occasionally LMN lesion, hemiparesis, paraparesis and quadriparesis are signs of UMN lesions, associated sensory, autonomic, cerebellar and other signs triangulate the lesion

Front 449

Describe the extent of the association cortex.

Back 449

the association cortex is almost everywhere, the association cortex is the seat of human cognitive ability and is defined as the remainder of the neocortex after excluding the primary sensory and motor regions, the term association refers to the fact that these regions of the cortex integrate information derived from other brain regions, constitutes about 75 percent of the cortical surface of the brain

Front 450

What is the study of cognition?

Back 450

essentially the study of association cortex functions, primary function of the association cortex is cognition

Front 451

What is cognition?

Back 451

selective attention to external stimuli and internal motivation, recognition and identification of stimuli (with regard to motivational state), planning responses to stimuli

Front 452

In terms behavioral psychology, what is the association cortex.

Back 452

the association cortex lowers the predictability of the stimulus-reponse bond, a bond that allows for the very accurate predictions of a response given a known stimulus in animals with relatively little association cortex

Front 453

What is the function of the parietal lobe in cognition?

Back 453

attending to complex stimuli in the external and internal environment

Front 454

What is the function of the temporal lobe in cognition?

Back 454

identifying the nature of complex information that has been pre-processed by parietal association cortical structures by matching it to some stored template

Front 455

What is the function of the frontal lobe in cognition?

Back 455

planning (and executing) a behavioral response to such stimuli, active aspects of attention as well

Front 456

What makes up the neocortex?

Back 456

association cortex along with the primary and secondary sensory and motor areas, it is six layers, however not all neocrotex is alike-cytoarchitectonically speaking, association is not the most differentiated and is not the newest cortex to emerge, what is new in humans is its relative mass, not all cortex is neocortex

Front 457

What is not classified as neocortex?

Back 457

hippocampal cortex and in general a great deal of the cortex on the underside of the brain is three or four layered archiocrotex, not six layered neocortex, while not typically referred to as association cortex, these cortically structures function much as association cortex

Front 458

What are the commonalities of all neocortical regions?

Back 458

1. each cortical layer has a primary source of inputs and a primary output target
2. each area has connections in the vertical axis (columnar) and connections in the horizontal axis (lateral)
3. cells with similar function tend to be arrayed in radially aligned groups
4. interneurons within specific layers provide for extensive local horizontal connections (within a given cortical layer) linking functionally similar groups of cells

Front 459

Describe the association cortex connectivity.

Back 459

The most extensive inputs to any given region of the association cortex come from other cortical regions (cortico-cortical connections). The immediately adjacent regions provide the most input, and levels of input taper down as regions of origin become more distant. Connections are ipsilateral and contralateral—the latter via the corpus callosum and anterior commussure.

Front 460

What is the major source of inputs to the association cortex?

Back 460

thalamus, some primary connections include:
1. other cortical regions -> pulvinar nucleus -> parietal association cortex
2. other cortical regions -> lateral posterior nucleus -> temporal association cortex
3. other cortical regions -> medial dorsal nucleus -> frontal association cortex

Front 461

What do the signals coming into the association cortex carry?

Back 461

The signals coming into the association cortices via the thalamus carry highly processed sensory and motor information from multiple areas of the cerebral cortex. (An important clinical implication of this is that thalamic lesions may produce symptoms that mimic cortical lesions).

Front 462

Where are some other strong inputs from? what are they involved in?

Back 462

Other strong inputs are from the brainstem and basal forebrain regions—dopaminergic, noradrenergic and serotonergic nuclei from the brainstem reticular formation and the cholinergic nuclei of the brainstem and basal forebrain. These pathways are involved in psychiatric and degenerative neurologic conditions and are a focal point of most of the effects of drugs aimed at altering emotional or cognitive symptoms.

Front 463

Where do the outputs of the association cortex go?

Back 463

Outputs from association areas go primarily to hippocampus, basal ganglia, cerebellum, thalamus, and other association cortices.

Front 464

What are the effects of lesions to the parietal lobe on the right side?

Back 464

1. defects appear to be in the spatial distribution of attention
2. contralateral neglect syndrome (hemi-neglect)
3. disruption in spatial frame of reference

Front 465

What are the effects of lesions to the parietal lobe on the left side?

Back 465

1. receptive aphasic deficits
2. sub-clinical defect in spatial distribution of attention
3. also right-left confusion, finger agnosia and others

Front 466

what are the effects of lesion to the temporal lobe on the right side?

Back 466

1. object agnosia-failing to match a highly processed sensory representation of an object to a stored template to achieve recognition
2. prosopagnosia-a special case of object agnosia, most broadly a failure to identify individual objects within a category while identifying the category

Front 467

What are the effects of lesion to the temporal lobe on the left side?

Back 467

1. anomia-the representation of the word for the recognized object is not accessible

Front 468

What are the effects of lesion to the frontal lobe on the right side?

Back 468

1. aprosodias
2. motor program deficits

Front 469

what are the effects of lesion to the frontal lobe on the left side?

Back 469

1. expressive aphasias
2. motor program deficits

Front 470

What are the effects of lesion to the frontal lobe in general (mostly prefrontal, medial and orbital-frontal)?

Back 470

1. compromise the ability to plan behavior in relation to the environment and to use memories to guide the appropriateness of behavior in various situations
2. defects in the impulse to act (lack of or too much)
3. defects in active attention

Front 471

Describe the clinical study of localization.

Back 471

The clinical study of the localization—relating specific cognitive functions to specific brain structures, is largely confined to patients who have suffered small and localized strokes, small penetrating injuries, small tumors, or to patients who have (again small) neurosurgical lesions. Such patients are a small subset of brain-injured patients.

Front 472

Describe the patients who are most likely to show symptoms due to injury to the association cortices?

Back 472

1. middle cerebral artery stroke
2. traumatic brain injury-particularly in decelerating brain injuries
3. neurologic degenerative diseases

Front 473

What is neuropsychological testing?

Back 473

The fundamental principals of neuropsychological testing are the same as those guiding a basic mental status examination (and many aspects of the basic neurological examination). What is added to the medical examination is the science of psychometrics.

Front 474

What domains are sampled in neuropsychological testing?

Back 474

1. perception
2. recent memory
3. visuo-spatial abilities
4. language
5. abstraction (thinking and reasoning)
6. executive functions
7. affect
8. impulse
9. insight

Front 475

What is behavioral neurology?

Back 475

Essentially it is the neurological study of syndromes associated with injury to the association cortex.

Front 476

What is lateralization?

Back 476

Lateralization refers to the functional specialization of one hemisphere for a particular cognitive activity.

Front 477

What is the difference between speech and language?

Back 477

Speech is distinct from language. About 200 phonemes are the basic building blocks of speech. You could say that speech is the ability to quickly and fluidly produce long sequences of phonemes. Assigning meaning to these arbitrary phoneme sequences is language.

Front 478

What is aphasia?

Back 478

Aphasia involves the compromise of essential language (symbolic) functions while leaving the sensory and motor components of verbal (and written) communication intact. The emphasis on the loss of the ability to produce or understand symbolic as opposed to realistic representations is important. The more symbolic the representation, the less understanding in the presence of an aphasia.

Front 479

Who is Paul Broca?

Back 479

Paul Broca was one of the first to associate language with the left hemisphere.

Front 480

Who is Carl Wernicke?

Back 480

Carl Wernicke distinguished receptive language deficits from expressive ones. Later Norman Geschwind elaborated on the distinctions first made by Wernicke resulting in our current heuristic model for the aphasias.

Front 481

What causes focal brain syndromes?

Back 481

-All focal brain syndromes can be considered to be the result of:
1. The destruction of a particular information processing center (e.g., Broca’s area, Wernicke’s) or
2. A disconnection of inputs to, or outputs from, such a center.
-Appreciating this leads to the basis for the current conceptual model of the aphasias.

Front 482

What is conduction aphasia?

Back 482

Conduction aphasia is a classic example of a disconnection syndrome.

Front 483

What are the different types of aphasia?

Back 483

Broca’s aphasia
Wernicke’s aphasia
Conduction aphasia
thalamic aphasias

Front 484

What is atherosclerosis?

Back 484

Atherosclerosis: decades-long process; progression favored by hypercholesterolemia, HTN, cigarette smoking, fatty streak, focal plaques and complicated fibrous plaques

Front 485

What are fatty streaks?

Back 485

Fatty streak: yellowish discoloration on intimal surface of blood vessel; microscopically, lipid –filled macrophages called “foam cells” (may be present even in childhood)

Front 486

What are focal plaques?

Back 486

Focal plaques: eccentric thickening at bifurcations; addition of massive extracellular lipids that displaced normal cells and matrix (late childhood or early Adolescence)

Front 487

What are complicated fibrous plaques?

Back 487

Complicated fibrous plaques: central acellular area of lipid covered by a cap of smooth muscle cells and collagen (third decade of life); with endothelial injury, caps thicken quickly as a result of thrombosis-dependent fibrotic organization

Front 488

What is the response to injury hypothesis of artherogenesis?

Back 488

Atherosclerosis begins as a response to chronic minimal injury to the endothelium and interactions among monocytes, lipoproteins, platelets, lymphocytes, and smooth muscle cells abet and continue the pathogenic process

Front 489

What are the 3 types of vascular injury?

Back 489

1. Type I injury: functional alterations of endothelial cells; primarily caused by
turbulence of blood flow
Other factors: HTN, hypercholesterolemia, circulating vasoactive amines, immunocomplexes, viral infections, and a chemical irritant in tobacco smoke
2. Type II injury: denuding of endothelium and superficial intimal injury accompanied by platelet deposition with or without thrombus formation
3. Type III injury: deep intimal and medial damage with marked platelet aggregation and mural thrombosis (usually seen following plaque rupture)

Front 490

What is the role of monocytes?

Back 490

Monocytes bind to endothelium after vascular cell adhesion molecule (VCAM) is expressed, insinuate themselves between endothelial cells . Once in the intima, they are transformed into macrophages and ingest modified lipids (primarily oxidized lipids).

Front 491

What are T lymphoctyes?

Back 491

T lymphocytes help to mobilize macrophages.

Front 492

Describe the oxidation of LDL-cholesterol.

Back 492

-“Scavenger receptor” on macrophages readily takes up oxidized LDL
-Oxidation induced by free radicals produced by macrophages, endothelial cells, or smooth muscle cells
-Oxidized LDL-cholesterol contribute to atherogenesis in 3 other ways: 1) its cytotoxic properties promote endothelial injury; 2) acts as chemoattractant for monocytes; and 3) inhibits egress of macrophages from plaques

Front 493

Describe smooth muscle cell migration and proliferation.

Back 493

-Makes up substantial bulk of plaque
-Factors involved: 1) growth factors (PDGF), 2) eicosanoids, 3) certain cytokines (eg, tumor necrosis factor, interleukin-1 and interferon), and 4) nitric oxide

Front 494

What are the role of platelets?

Back 494

-Contribute to formation of capsule of “fatty lesions”, of subendothelial “fibrointimal lesions” and stimulate migration and proliferation of smooth muscle cells
-Platelet activation: incited by exposed collagen; activated platelets acquire enhanced capacity to catalyze interactions between activated coagulation factors
-Platelet adhesion: promoted by damage to intimal surface, toxic products released by macrophages; platelets adhere to subendothelial receptors (mainly, GP-Ib-IX)
-Platelet aggregation: interplatelet bridging (receptor GP IIb-IIIa)

Front 495

Describe thrombosis.

Back 495

-Activation of coagulation cascade culminates in generation of thrombin which converts soluble fibrinogen to fibrin forming a blood clot. Fibrin molecules aggregate together, trapping platelets, erythrocytes, and leukocytes
-Thrombosis on atherosclerotic plaque may precipitate acute episodes of transient ischemia and ischemic stroke (as well as MI and unstable angina)

Front 496

What determines the severity of brain dysfunction and thus the severity of stroke?

Back 496

Duration, severity and location of focal cerebral ischemia determine the severity of brain dysfunction and thus the severity of stroke.

Front 497

What is the requirement of constant energy supply?

Back 497

The transient change in voltage induced by the action potential is determined by the concentration of ions on either side of cell membrane. Maintaining these ionic gradients is an energy-consuming process that requires constant supply of glucose and oxygen to the neuron.

Front 498

What happens with inadequate energy supply?

Back 498

-Cellular energy stores depleted due to lack of glucose and oxygen
-“Leaky” membrane leads to K+ and ATP loss
-5-10 minutes required for irreversible brain damage
-One or more branching mechanisms may independently lead to cell death:
-May involve 1) deterioration of ion gradients or 2) effects of anaerobic metabolism

Front 499

Describe the deterioration of ion gradients leading to excitotoxicity.

Back 499

• Anoxic depolarization (equilibrium of intracellular and intracellular ions) causes potassium exit & sodium, chloride and calcium entry
• Massive release of glutamate & aspartate
• Glutamate further activates sodium & calcium ion channels in the neuron membrane ---- cytotoxic edema
• Activation of calcium channels result in furher influx of calcium
• Entry of calcium through N-methyl-D-aspartate (NMDA) channel activation: further depletion of energy, activation of proteases, lipases, and nucleases
• These enzymes & their metabolic products (oxygen free radicals) cause cell death
• Neuroprotective agents: drugs that would block above steps; still investigational

Front 500

What is the ischemic penumbra?

Back 500

• Core ischemic zone: blood flow below 10% to 25 %, severe ischemia can result in necrosis of neurons and glial cells
• Penumbral zone: mild to moderately ischemic tissue between normally perfused area and the area in which infarction is evolving; ailing but salvageable tissue; supplied by collaterals; extent varies directly with the number and patency of collateral arteries; if reperfusion not established in the early hours, cells may die

Front 501

What are the cerebral infarcation/effects of edema?

Back 501

• Edema may cause further damage by compressing neurons, nerve tracts, and cerebral arteries
• May increase intracranial pressure (ICP) or shift structures within cranial vault
• Two major types of edema: 1) Cytotoxic: onset within minutes to hours; swelling of all cellular elements of the brain (neurons, glia, endothelial cells); increased intracellular calcium activates phospholipases and the release of arachidonic acid, leading to release of free radicals and infarction, 2) Vasogenic: increase in extracellular fluid volume due to increased permeability of brain capillary endothelial cells (onset within hours to days)

Front 502

Describe the anaerobic glycolytic pathways.

Back 502

• Compensate for loss of oxygen & provide source of energy
• Produce damaging byproducts including lactic acid and hydrogen ions (latter facilitate ferrous-iron-mediated free radical mechanisms; irreversibly affect neuronal integrity)

Front 503

What is transient ischemic attack (TIA)?

Back 503

A clinical syndrome characterized by an acute loss of focal brain or monocular function with symptoms lasting less than 24 hrs and which is thought to be due to inadequate cerebral or ocular blood supply, without ischemic changes in Diffusion Weighted Imaging (DWI)

Front 504

What is stroke?

Back 504

Clinical syndrome characterized by an acute loss of focal brain or monocular function with symptoms lasting greater than 24 hrs and which is thought to be due to inadequate cerebral or ocular blood supply.

Front 505

Describe the importance of cerebrovascular accident or brain attack.

Back 505

 Third leading cause of death
 750, 000 cases/year
 Leading cause of significant disability
 Cost: $40 billion/year

Front 506

What are the different types of stroke?

Back 506

 Ischemic, 80% (non-hemorrhagic, bland stroke)
-thrombosis, 50% (small & large-vessel), usually when sleeping or lying down
-embolism, 30% [now believed significantly higher], usually when active
 Hemorrhagic, 20%
- intracerebral (HTN (hypertension) as risk)
- subarachnoid (aneurysm)

Front 507

What are some non-modifiable risk factors of stroke?

Back 507

 Age
 Gender (male)
 Race (asians, blacks, females more prone to intracranial stenosis)
 Diabetes mellitus (treated or not)
 Prior stroke or transient ischemic attack
 Family history
 Asymptomatic carotid bruit (playing alone and then listening to colleagues and then hear a bruit when they are asymptomatic)

Front 508

What are some less well-documented non-modifiable risk factors of stroke?

Back 508

 Geography/ climate
 Socioeconomic factors

Front 509

Describe diabetes mellitus as a non-modifiable risk factor of stroke.

Back 509

 Non-modifiable risk factor
 Stroke 2.5 – 4 X more common
 Microvascular complications (retinopathy, nephropathy, neuropathy, stroke), Macrovascular complications: MI, Peripheral Vascular Disease (PVD), stroke)

Front 510

Describe hypertension as a treatable risk factor for stroke.

Back 510

Hypertension: accelerates atherosclerosis, promotes microaneurysm formation (in the subcortical areas of the brain, why HTN is a known culprit for hemorrhage)

Front 511

Describe heart disease as a treatable risk factor for stroke.

Back 511

Heart disease (atrial fibrillation, recent MI, valvular disease)

Front 512

Describe cigarette smoking as a treatable risk factor for strok.

Back 512

Cigarette smoking: increases BP, CO, platelet aggregation 50% risk overall, if stop smoking then risk goes down, but chances of lung cancer are a lot higher, High cholesterol & lipids, obesity, inactivity

Front 513

What are some less well documented risk factors for stroke?

Back 513

 Alcoholism-it alters platelet function, may give rise more to hemorrhagic stroke than bland stroke
 Drug abuse (cocaine, methamphetamine), if taking slimming pills, more you do these durgs the more prone the vessels are to microhemorrhage
 Bacterial infections, tonsilitis esp. in kids, can get some type of vasculitis (is a strong risk factor for stroke)

Front 514

What are some potential genetic risk factors for stroke?

Back 514

 Presence of Apolipoprotein E4 forms part of VLDL,
 High homocysteine level (may be born with high homocysteine, most common cause is folate deficiency)
 Factor V mutation resistance to anticoagulant protein C

Front 515

What are the stages of atherosclerosis and thrombosis?

Back 515

1. Fatty streak-fatty streak at age 11 or 12
2. Focal plaques
3. Complicated fibrous plaques

Front 516

What role do statins have on atherogenesis?

Back 516

 Statins prevent the Oxidation of LDL cholesterol (oxidized LDL promotes more injury, attracts more monocytes, inhibits egress of macrophages from plaques
 Smooth muscle cell migration and proliferation, makes plaque stable

Front 517

What is the role of platelets on atherogenesis?

Back 517

1. adhesion
2. activation
3. aggregation

Front 518

Describe thrombosis.

Back 518

 Activation of coagulation cascade
 Generation of thrombin (converts fibrinogen to fibrin)
 Trapping of platelets, erythrocytes, monocytes (red fibrin clot)
 Thrombosis on atherosclerotic plaque may precipitate cerebrovascular accident (CVA), MI or unstable angina

Front 519

What is the difference between diffusion weighted MRI and perfusion-weighted MRI?

Back 519

-diffusion-weighted can display an area of infarction
-perfussion-weighted can show the wider area of ischemia, the difference between the lesion as shown on perfusion-weighted MRI and diffusion weighted MRI represents tissue that is potentially salvageable

Front 520

Describe the core zone in the ischemic penumbra.

Back 520

 Core zone: severely ischemic, blood flow below 10%-25%
 Penumbral zone: viable but ailing since collateral flow is inadequate to maintain neuronal demand for oxygen and glucose

Front 521

What are the effects of edema/cerebral infarction?

Back 521

 The infarcted tissue causes edema, shift of brain substance causing further damage by compressing other structures (neurons, nerve tracts and cerebral arteries)
a) Cytotoxic edema: neurons, glia, and endothelial cells swell (within minutes)
b) Vasogenic edema: increased permeability of capillary endothelial cells to serum proteins (delayed onset)

Front 522

Describe the deterioration of ion gradients.

Back 522

 Egress of K+, ingress of Na+, Cl-, Ca++
 Massive release of glutamate and aspartate (excitatory)
 Activation of Na+ and Ca++ ion channels
 Accumulation of Na+ and Ca++, accompanied by inflow of water ---- cytotoxic edema
 Entry of Ca++ causes activation of proteases, lipases, nucleases --- damage of cell membranes, genetic material, structural proteins --- cell death

Front 523

What are the 5 basic objectives of emergent evaluation of stroke patients?

Back 523

 Confirm that stroke is the cause of symptoms (make sure it is not due to bell’s palsy)
 Provide information about possible reversibility of the pathology
 Give clues about etiology
 Predict likelihood of complications; and
 Begin appropriate treatment

Front 524

What does the AHA stroke council recommended for the assessment of a person with a suspected stroke?

Back 524

 EMS should be instructed in the rapid recognition, evaluation, treatment and transport
 Baseline assessment within minutes, CT scan ASAP; use National Institutes of Health Stroke Scale (NIHSS)

Front 525

What characterizes the immediate evaluation of persons suspected with stroke?

Back 525

1. Airway
2. Vital signs
3. General medical assessment (including evidence of injury, cardiovascular abnormalities)
4. Neurological assessment (frequent)

Front 526

What is the clinical presentation of acute stroke?

Back 526

 Can be maximal at onset, stepwise (“stuttering”), or fluctuating
 Ischemic & hemorrhagic: clinical presentations overlap
 DDx: seizures (Todd’s paralysis), brain tumors, hypoglycemia, other metabolic disturbances

Front 527

What does the middle cerebral artery supply?

Back 527

 supplies the lateral surface of hemisphere except for:
1. frontal lobe
2. strip along superomedial border of frontal lobe
3. lowest temporal convolutions
 Most frequently affected in embolic & thrombotic stroke

Front 528

Describe a left MCA territory stroke: dominant hemisphere.

Back 528

 Cortex & white matter (WM) of the lateral & inferior aspects of frontal lobe, motor cortex (areas 4 & 6, center for contraversive eye movements, motor speech area of Broca), cortex & WM of the lateral parietal lobe (sensory cortex, angular & supramarginal gyri), lateral & superior parts of the temporal lobe, insula

Front 529

How does a left MCA territory stroke: dominant hemisphere present clinically?

Back 529

global aphasia, eyes deviated to left (when have a seizure eyes deviate away from where it is firing, if destructive then eyes deviate to site of lesion); right hemiparesis (arm weaker than leg), right hemisensory deficits, right homonymous hemianopsia (right visual field cut)

Front 530

Describe right MCA territory stroke: non-dominant hemisphere.

Back 530

 Aphasia not present
 Spatial disorientation (with disorder of body image), left hemineglect, anosognosia
 Dysarthria may be present

Front 531

Describe a posterior circulation (vertebrobasilar territory) stroke.

Back 531

 Ataxia, gait abnormalities
 Diplopia, oscillopsia, nystagmus, dysconjugate eye movements
 Nausea & vomiting (center is in area post-rema)
 Crossed hemiparesis, hemisensory deficits
 Headache more common

Front 532

Describe the evaluation and work-up of a stroke patient.

Back 532

 History and PE
 Computed Tomography (CT) scan of the head
 12-lead EKG, chest X-ray
 Complete blood count, PT, PTT
 Chemistries (sodium, phosphate, glucose abnormalities may mimic stroke)
 Urine and serum toxicology (drugs and alcohol)

Front 533

What are some other neuroimaging techniques and ancillary tests?

Back 533

 Magnetic Resonance Imaging (MRI), Diffusion Weighted Imaging (DWI), Magnetic Resonance Angiography (MRA)
 Ultrasound (Carotid Duplex, Transcranial Doppler, 2-D echo)
 Conventional Angiography
 Single Photon Emission Computed Tomography (SPECT)
 Positron Emission Tomography

Front 534

What other tests may be required under special circumstances?

Back 534

 Cervical spine x-ray
 Arterial blood gas
 Lumbar puncture
 Electroencephalogram (EEG)

Front 535

Describe emergent supportive care.

Back 535

 Maintenance of adequate tissue oxygenation: protecting the airway, O2 inhalation
 Maintaining optimal blood pressure (autoregulation faulty or lost in stroke patients
 Management of blood glucose abnormalities (hyperglycemia associated with poorer prognosis)
 Management of fever and infections (ischemia worsened by hyperthermia, improved by hypothermia

Front 536

What are the therapies with FDA approval?

Back 536

 IV TPA (< 3hours)
 IA fibrinolysis (< 6 hours)
 IA MERCI retriever < 8 hours
 Endovascular temperature control

Front 537

Describe acute stroke treatment.

Back 537

 Intravenous recombinant tissue plasminogen activator (TPA): within 3 hours of stroke symptom onset
 Intraarterial TPA: within 6 hours; MCA territory stroke by angiography

Front 538

What are some known factors that cause stroke progression?

Back 538

 Hypotension
 Hyperglycemia
 Hyperthermia
 Infection
 Cerebral hypoperfusion

Front 539

What is the treatment of brain swelling?

Back 539

 Cerebral perfusion pressure =MAP-ICP
 Fluid Restriction (1200 ml /day/m2)
 Controlled hyperventilation: 25 mm Hg
 Mannitol, 0.25 mg/kg IV over 20 minutes; repeat PRN, serum osmolality maintained in the range of 300-320mOsm/l
 Barbiturate coma, with ICP monitoring (subarachnoid bolt, IV catheter or Camino catheter): maintain CPP greater than 50 mmHg; pentobarbital serum level of 2-4 mg/dl
 Surgery (wait 2 weeks)

Front 540

Describe the management of cerebral edema, INC intracranial pressure and hydrocephalus.

Back 540

 Brain edema peaks at 3-5 days
 Treatment includes:
1. hyperventilation (lower PCO2)
2. osmotic diuretics
3. drainage of CSF (ventriculostomy)
4. surgery (lobectomy)

Front 541

Describe neuroprotective agents.

Back 541

 Several trials going on
 So far, trial on one free-radical scavenger showed positive results
 Phase II trials have proven beneficial; Phase III (human efficacy trials) non-benefial to negative
 Common measures may “neuroprotect”

Front 542

Describe stroke prevention.

Back 542

 Anticoagulants (Heparin, Warfarin)
 Antiplatelets (aspirin, clopidogrel dipyridamole/ASA combination, ticlopidine)
 Carotid endarterectomy if indicated
 Risk factor control!

Front 543

Describe the concept of stroke teams and stroke units.

Back 543

 “Time is brain”
 Stroke awareness
 Common mistakes may lead to fatal consequences
 Boutique stroke neurology: Patients will receive best care; length of stay shortened

Front 544

what is learning

Back 544

adaptive change in behavior caused by experience (observable change in activity important to the welfare of the organisms

Front 545

what is memory

Back 545

internal storage and recall of previously learned behaviors

Front 546

what is foregetting

Back 546

loss of memory function, retrograde vs. anterograde amnesia

Front 547

What are the classifications of memory?

Back 547

by function and temporality

Front 548

Describe the functional classification of memory

Back 548

1. declarative (explicit)-storage and recall information available to the conscious mind, 2 subtypes (EPISODIC memory-specific personal events, can be looked up, SEMANTIC memory-generic facts and meaning about the world around us, the gist (of course semantic memory must somehow be extracted from episodic experience)
2. non-declarative (implicit, procedural)-storage and subconscious retrieval of skills and associations, performance skills (how to) and interpretation 9attractive funny) can’t be readily verbalized

Front 549

Describe the temporality classification of memory

Back 549

1. immediate-rapid decay (seconds or less) orf a sensory experience
2. working-retention and recall of events for a period of seconds to minutes (actually attentional looping of immediate memory and LTM with suppression of distraction stimuli
3. short-term-minutes to a few hours
4. long-term-permanently available (due to storage of engram)

Front 550

What is the difference between biological memory and CPU memory?

Back 550

unlike CPU memory, biological memory arises from activity of the processors (neurons) themselves, in the context of behavior. the brain is not a computer

Front 551

Describe the epidemiology of dementia.

Back 551

Worldwide, at least 7 per cent of persons over 65 and nearly half of those over 85 have some form of dementing illness
Including milder forms of dementia, the prevalence may rise to 15 per cent of the elderly
Prevalence closer to 8-10 per cent in US and other developed countries with longer life spans

Front 552

What is the effect of age on dementia.

Back 552

The epidemic nature of dementia derives from the sharp rise in its incidence with age
The elderly population is increasing rapidly both in absolute numbers and percentage of the population
Proportion of US population > 65 years of age
Moreover, the most rapidly growing age group are the very old, those 85 and older, who may account for 18.2 million people by mid 21st century

Front 553

Describe the financial burden of dementia

Back 553

In the US, dementia costs over $100 billlion per year
Approximately 10 per cent of all health care expenditures
Dementia patients account for a disproportionate use of health care resources
Dementia patients account for more hospitalization days than any other psychiatric condition among geriatric age group
Immense burden not only to patients but to their caregivers, the health care system, and society as a whole

Front 554

What is the definition of dementia?

Back 554

Dementia is a syndrome of acquired, persistent intellectual impairment that is due to brain dysfunction

Front 555

How is dementia diagnosed?

Back 555

Operationally, dementia implies impairment in three or more of the following domains of mental capacity: (Memory, Praxis, Executive Functions, Language, Calculations, Personality, Perception, Semantic Knowledge, Emotional Expression or Awareness
Compromise documented by mental status assessment, either by bedside mental status evaluation, clinical rating scales or by neuropsychological testing

Front 556

Describe acquired dementia.

Back 556

congenital mental, retardation and developmental delay

Front 557

Describe persistent dementia.

Back 557

delirium

Front 558

Describe multiple cognitive deficits.

Back 558

isolated, neuropsychological deficits (amnesia or aphasia)

Front 559

What are some dementia myths?

Back 559

(1) Dementia is a global impairment of intellectual function
(2)Dementia always impairs memory
(3) Dementia always impairs insight; patients aware of their deficits don’t have dementia (4) Dementia is a cognitive disorder and never primarily a behavioral disorder
(5) Dementia is an inevitable part of aging and is synonymous with “senility”
(6)Dementia is synonymous with Alzheimer’s disease
(7) Dementia cannot have an acute onset
(8) Dementia is an untreatable disorder

Front 560

What are some characteristics of AD?

Back 560

-Onset usually after age 65
-Gradually progressive course
-Early memory impairment with aphasia, agnosia, perceptual impairment, dysexecutive syndrome

Front 561

What are some characteristics of vascular dementia?

Back 561

-Stepwise deterioration
-Focal neurological deficits
-Evidence of vascular disease by history, exam and neuroimaging

Front 562

What are some characteristics of dementia with Lewy bodies?

Back 562

-Fluctuating cognition, alertness
-Visual hallucinosis and psychosis
-Parkinsonism
-neuroleptic drug sensitivity

Front 563

What are some characteristics of frontotemporal dementia?

Back 563

-Onset usually before age 65
-Insidious onset and gradual progression
-Alteration of judgment and social conduct
-Progressive aphasia, relatively intact memory

Front 564

Describe the mental status assessment.

Back 564

The ability to demonstrate alterations in mental functions is critical in the evaluation of dementia
Mental status evaluation (MSE) is the essential tool for this task
MSE can distinguish the intellectual changes of dementia from those associated to delirium, isolated cognitive deficits, normal aging and other conditions
Identifies patterns and profiles of neurobehavioral dysfunction which suggest specific dementing diseases
Establishes and communicates severity of dementia and follow course of patients over time

Front 565

Describe the fundamental sphere of mental function.

Back 565

-Arousal-Response to verbal or physical stimulation
-Attention-Ability to focus on selected stimuli without distraction
-Mental Control-manipulation of attention, initiation and performance action

Front 566

Describe the instrumental sphere of mental function.

Back 566

-Language-Symbolic communication: naming, verbal fluency and comprehension
-Memory-New learning and information retrieval
-Perception (visuospatial)-Interpretation of sensory input, drawing and copying
-Praxis-Integration and performance of learned, complex motor act
-Calculations-Interpretation of numeric symbols and calculation
-Semantic Knowledge-Knowledge of words, concepts, meanings
-Executive Functions- Goal-directed behavior, strategic planning and execution

Front 567

Describe the behavioral fundamental sphere of mental function.

Back 567

-Personality and Social-Social interactions and self-regulation
-Emotion-Emotional reactivity and engagement, awareness of others

Front 568

Describe the arousal and attention elements of a screening mental status evaluation.

Back 568

-Response to physical and verbal stimuli
-Assess novel tasks, digit span, orientation to time and place

Front 569

Describe the language element of a screening mental status evaluation.

Back 569

-Object naming (at least six common items)
-Category word list generation

Front 570

Describe the memory element of a screening mental status evaluation.

Back 570

-Orientation for time and place
-Word list registration and recall

Front 571

Describe the perception and construction.

Back 571

-Copy a cube or intersecting pentagons
-Clock drawing task

Front 572

Describe the personality and emotion elements of a screening mental status evaluation.

Back 572

-Observe propriety of interpersonal conduct and emotional behavior

Front 573

What are some mental status behavioral rating scales?

Back 573

-mini-mental state examination (MMSE) (most popular)
-mattis dementia rating scale (DRS)
-blessed dementia scale (BDS)

Front 574

Describe the mini cog mental status evaluation.

Back 574

Mini Cog combines the 3 item recall and Clock Drawing Test
Studied as a screening test for dementia among 249 community dwelling adults and compared with DSM-IV and NINCDS-ADRDA diagnostic criteria and other screening tests, the Mini Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI)
Participants were judged to be demented if either the 3 item recall score was 0 or the 3 item recall score was 1 to 2 and CDT error score was rated between 1 (mild) and 3 (severe)
With this algorithm, Mini Cog had sensitivity of 99%, highest among the three instruments tested, and specificity of 93%

Front 575

Describe the utilization of the standardized neuropsychological tests.

Back 575

Can confirm dementia or impairment in mental status domains
Useful when thorough and precise analysis of cognitive function is required, and when mild deficits are suspected
Useful in quantifying cognitive impairment and residual strengths
Can help monitor progression or recovery; assess interventions
Useful in distinguishing dementia from depression

Front 576

Describe normal aging vs. dementia.

Back 576

Normal aging results in a characteristic pattern of cognitive and behavioral changes (this is not dementia)
Most consistently manifests as a generalized slowing of both intellectual and physical performance

Front 577

What are some typical features of the classical aging pattern?

Back 577

-Decreased complex or sustained attention
-Interference from redundant or irrelevant material
-Preserved crystallized intelligence (old solutions)
-Decreased fluid intelligence (new information for novel solutions)
-Relatively stable verbal IQ
-Decline in performance IQ
-Decreased working memory
-Slowed retrieval of stored memory

Front 578

Describe mild cognitive impairment.

Back 578

An amnestic syndrome in which pts have isolated impairments in memory beyond those of age-matched and education-matched cohorts
MCI pts show memory loss similar to that seen in AD but lack deficits in other domains and therefore do not have dementia
MCI “converts” to dementia at a rate of 10-15% per year while the conversion rate to AD in absence of MCI is 1-2% for general pop’n
MCI is emerging as a candidate transitional state between normal and AD and increasing diagnostic accuracy for MCI is an area of intense interest
At autopsy, MCI resembles AD with 60% or more that demonstrate neocortical and limbic neuropathology characteristic of AD

Front 579

What is the differential diagnosis for delirium vs. dementia?

Back 579

look at slide 20

Front 580

What is the epidemiology concerning AD?

Back 580

Currently 2-4 million Americans have AD
Mean cost of care per patient per year estimated at $20-30 K
Prevalence doubles approximately every five years after age 60: 1% affected at age 60, 2% at age 65-69, 4% at age 70-74, 8% at age 75-79 and ultimately between 26 and 45% of those 85 and older
AD may play a role in one-third of all deaths in North America
With increasing size of the aged population, it is predicted that in US alone, the number of persons with the disease may reach 14 million by year 2050

Front 581

What is the diagnostic criteria for probable AD?

Back 581

-Dementia established by clinical examination and documented by mental status scales
-Deficits in 2 or more cognitive domains
-Progressive deterioration of memory and other cognitive domains
-Absence of delirium
-Onset between ages 40 and 90
-Exclusion of systemic/brain disorders capable of producing dementia

Front 582

What is the diagnostic criteria for possible AD?

Back 582

-Atypical presentation or course of a dementia of unknown etiology
-Progressive deterioration of a single cognitive domain
-Presence of a systemic or other brain disorder not thought to be the cause of dementia

Front 583

Does a diagnosis of AD during life guarantee the presence of AD at autopsy?

Back 583

Despite these formal clinical criteria, a diagnosis of AD during life does not guarantee the presence of AD at autopsy
In early follow-up studies, accuracy of the clinical diagnosis 50-60%
Following implementation of NINCDS-ADRDA and DSM-IV criteria, the sensitivity of clinical diagnosis rose to 85-90%

Front 584

Describe the memory clinical characteristics of AD.

Back 584

-AD often begins with a 3-6 year preclinical period during which episodic memory deficits occur without other symptoms of dementia
-encoding deficit -> DEC delayed recall -> accelerated forgetting relative preservation of (Long-term memory, Procedural memory)

Front 585

Describe the language clinical characteristic of AD.

Back 585

In AD, initial word-finding difficulty progresses to poor naming (dysnomia) and impaired comprehension
In early disease, there may be poor word list generation, particularly for words in a given semantic category
As AD progresses, dysnomia worsens with paraphasias and spontaneous speech becomes increasingly empty
With further progression, impaired comprehension of speech and writing are apparent
Phonology and basic syntax are relatively spared

Front 586

Describe the perception and construction clinical characteristic of AD.

Back 586

Visuospatial impairment is another early manifestation of AD
Evident as inability to orient themselves in their surroundings
Simple drawing tests reveal an inability to copy elementary figures or 3-dimensional representations accurately
Left hemispatial neglect has been documented in association with decreased right parieto-occipital metabolism and blood flow
As disease progresses, agnosic difficulties may appear

Front 587

Describe executive dysfunction as a clinical characteristic of AD.

Back 587

Subtle executive impairments occur early in AD
Frontal-executive disturbances: (impaired insight, decreased goal-directed behavior, poor abstractions and reasoning)
Lack of concern for deficits may delay patients presentation for evaluation

Front 588

Describe the behaviorl symptoms associated with the clinical characteristics of AD.

Back 588

Personality and social behavior not markedly changed in early AD
Preserved behaviors allow patients to continue functioning socially and leads others to underestimate or excuse their cognitive deficits

Front 589

What are the range of behavioral symptoms?

Back 589

1. indifference and apathy
2. agitation, anxiety, aggression
3. disinhibition and wandering
4. depression (common and variably reported)

Front 590

What are the symptoms associated with AD patients with delirium?

Back 590

Nearly half of all AD patients exhibit delusions during the course of the disease. This generally carries a worse prognosis due to association with greater and more rapid cognitive decline: (Theft (35%), Phantom boarder syndrome (17%) , Interaction with deceased (18%), Copgras-like syndrome (17%), General persecutory (18%), Spousal infidelity (8%))

Front 591

Describe sleep, appetite and sexual behavior in AD patients.

Back 591

AD patients experience disturbances of sleep, appetite and sexual behavior (sleep fragmentation, increased latency to REM, Diminished SWS and REM sleep, REM behavior disorder, Nocturnal agitation (sundowning))

Front 592

What are the neurological symptoms of AD?

Back 592

Neurologic exam generally normal during first stage of disease
During later stages, motor system abnormalities appear: (extrapyramidal (parkinsonian) rigidity (EPS), gegenhalten, spasticity)
Eye movement difficulties: tracking errors, hypometric saccades, gaze impersistence
In later stages, spontaneous non-startle myoclonic jerks and seizures may occur
In terminal stages, AD patients become non-ambulatory and often mute, develop fecal and urinary incontinence and primitive and disinhibited cortical reflexes

Front 593

Describe the disease course and prognostic factors.

Back 593

Mean survival after symptom onset is 10.3 yrs, with a range of 2-20
Low intellect or educational level correlates with risk for AD in most but not all studies
Negative prognostic factors include a later age of onset of symptoms, prominent delusional and other psychotic symptoms, and comorbid cerebrovascular disease, heart failure, history of alcohol abuse and institutionalization
Death ultimately results from complications of terminal stage illness

Front 594

What are the principal findings in the preclinical stage (1-3 years) of AD?

Back 594

-Mild Cognitive Impairment
-Memory: new learning defective, remote recall mildly impaired
-Perception: topographic disorientation, poor complex constructions
-Language: poor word-list generation, mild dysnomia, empty speech
-Behavior: indifference, irritability, sadness or delusions in some
-CT/MRI: atrophy of mesiotemporal and hippocampal structures
-PET/SPECT: bilateral posterior parietal hypometabolism/hypoperfusion

Front 595

What are the principal findings in stage 2 (2-10 years) of AD?

Back 595

-Memory: recent and remote recall more severely impaired
-Perception: poor constructions, spatial disorientation, visual agnosias
-Language: fluent aphasia, anomia, paraphasia, poor comprehension
-Other cognitive impairment: apraxia and acalculia
-Behavioral: indifference or irritability, sadness or delusions
-Motor system: restlessness
-EEG: slowing of background rhythm
-CT/MRI: normal or ventricular dilatation and sulcal enlargement
-PET/SPECT: temporoparietal hypometabolism/hypoperfusion

Front 596

What are the principal findings in stage 3 (8-12 years) of AD?

Back 596

-Cognitive functions: severely deteriorated
-Speech: echolalia, dysarthria, mutism
-Motor: limb rigidity, gegenhalten, flexion posture
-EEG: diffusely slow
-CT/MRI: Advancing atrophy
-PET/SPECT: bilateral temporoparietal and frontal hypometabolism/hypoperfusion

Front 597

Describe laboratory investigation for AD.

Back 597

Although no definite laboratory test for AD, diagnostic tests can strengthen the clinical diagnosis by exclusion of other diseases
This depends on routinely obtaining: (blood count, thyroid function tests chemistries, Vitamin B 12, CT or MRI (recommended), genetic or CSF studies (only in select cases))
Other tests are supplementary and may be considered in select situations

Front 598

Describe neuroimaging investigation for AD.

Back 598

Brain CT or MRI may disclose other disorders masquerading as AD
In AD, imaging may be normal or may demonstrate non- specific generalized cerebral atrophy or focal atrophy in the mesiotemporal regions and hippocampal structures
On MRI, degree of hippocampal volume loss correlates well with degree of cognitive impairment and amount of hippocampal pathology at autopsy

Front 599

Describe functional neuroimaging for AD.

Back 599

Cerebral blood flow and metabolism are consistently reduced in AD and can be demonstrated with either positron emission tomography (PET) or single photon emission computed tomography (SPECT)
Decreases in metabolism are most prominent in the parieto-temporal regions bilaterally, followed later by reduction in the frontal association areas
In early stage disease, parietotemporal hypometabolism may be unilateral and at least one side is hypometabolic in 92% of AD patients (Salmon E et. al., J Nucl Med 1994;35:391-8)
In pts with clinically probable AD, SPECT may afford an additional 10-15% of accuracy of the clinical diagnosis
While useful, PET and SPECT are in no way pathognomonic of AD

Front 600

Describe neuropathology in AD.

Back 600

The definitive diagnosis of AD requires clinicopathologic correlation depending upon an identifiable clinical pattern combined with characteristic neuropathologic findings

Front 601

What are the neuropathological hallmarks of AD?

Back 601

-NFTs and neuritic plaques-primarily in cerebral cortex and in greater number and concentration than expected for the patient’s age
-Granuovacuolar degeneration
-Amyloid angiopathy
-Brain atrophy
-Neuronal cell loss-temporolimbic areas (entorhinal cortex > CA1 hippocampus, amygdala), temporoparietal neocortex, basal forebrain, brainstem
-Loss of synapses

Front 602

What are neurofibrillary tangles?

Back 602

NFTs consist of neurofibrils which are combined into bizarre shapes
Occur preferentially in pyramidal neurons of the neocortex, hippocampus and amygdala, in addition to the raphe nuclei and locus ceruleus
EM reveals that they are paired helical neurofilaments 100 Å wide with the helical twist occurring every 800 Å
Disrupt normal intracellular axonal transport facilitated by neurofilaments
NFT neurofilaments contain microtubule-associated protein tau in hyperphosphorylated state

Front 603

What are neuritic plaques?

Back 603

Neuritic plaques are spherical, silver-staining structures 5 to 150 Å in diameter located outside the neuron
They are concentrated in cerebral cortex and hippocampus but are also known to occur in the striatum, amygdala and thalamus
Central core of plaque contains beta-amyloid (Ab) around which are degenerating dendrites and axons, some of which contain paired helical filaments like those found in NFTs
Apolipoprotein e4 found within plaque
Inflammatory mediators found around plaque periphery
Reduced and altered synapses within the plaque disrupt intercellular communication and impair the essential function of synapses in learning, memory and cognition

Front 604

What are the cholinergic and other neurotransmitter changes in AD?

Back 604

Cholinergic abnormalities thought to play an important role in memory and cognitive changes associated with AD
Neuronal death and dysfunction in Nucleus Basalis of Meynert leads to reduction in choline acetyltransferase (ChAT) and subsequent deficiency in presynaptic Ach production
Cholinergic activity is reduced 80-90% in affected cortical regions
In contrast to AD, in MCI there is evidence of early upregulation of ChAT
Glutamate neurotransmission probably abnormal, with potential for increased vulnerability to excitotoxic cell death
Deficiencies of NE and serotonin along with reduced a-1 and a-2 adrenergic receptors and 5-HT1 and 5-HT2 receptors may influence the behavioral manifestations of AD

Front 605

What are some established AD risk factors?

Back 605

-Advanced age
-Family history of dementia
-Down’s syndrome
-Presinilin and APP gene mutations
-Apolipoprotein E e4
-Head trauma, particularly in preceding ten years
-Low educational attainment
-Small head size

Front 606

What are some possible AD risk factors?

Back 606

-Alcohol or other drug abuse
-Aluminum, zinc, mercury exposure
-Inverse association with smoking
-Advanced maternal age
-Family history of Down’s syndrome
-Cerebrovascular disease
-Dyslipidemia, elevated homocysteine
-Low B12, Folate, Thyroid disease

Front 607

What are some theories of pathogenesis of AD?

Back 607

-Amyloid cascade hypothesis
-Tau and Tangle hypothesis
-Cholinergic hypothesis
-Multiple neurotransmitter deficits
-Aluminum and other toxic exposure
-Chronic infection and inflammation
-Accelerated aging and decreased plasticity

Front 608

What are some therapeutic strategies for AD?

Back 608

1. antiamyloid-secretase inhibitors, immunization
2. tau normalization-kinase inhibitors
3. cholinergic-cholinesterase inhibitors
4. glutamatergic-cholinesterase inhibitors
5. antioxidative-vitamin E, selegiline, ginkgo biloba extracts
6. hormonal-nerve growth factor, estrogen
7. reduction of other risk factors-statins, vitamin B6, B12, folate

Front 609

What is the definition of spinal trauma?

Back 609

 injury has occurred to any of the following structures in the vertebral column: Bony elements, Soft tissues, Neurological structures

Front 610

What are two concerns of spinal trauma?

Back 610

– Instability of the vertebral column
-Actual or potential neurological injury

Front 611

What is the epidemiology of spinal cord injuries?

Back 611

• The annual incidence of SCI in developed countries varies from 11.5- 53.4/million population
• Mortality of 48- 79% at the time of the accident or on arrival to hospital
• Deaths after admission: 4.4- 16.7%
• 11% of all SCI die within the first hospitalization
• The 1-year case fatality rate for all patients is 46%
• Case fatality rate of 13% for those who reached the hospital alive
Over the past 20 years the incidence has stabilized but survival rate has increased
 Average age at time of SCI is rising
 Prevalence rates between 130 and 1124 per million
 Prevalence date indicate that the median age of persons with SCI is approximately 27 years
 Patients spend on average 171 days of their initial year in hospital
 Initial hospitalization will cost $US95,000; life time will cost $US500K- >$US2mil

Front 612

What is primary injury?

Back 612

Involves the initial mechanical injury due to local deformation and energy transformation

Front 613

What is secondary injury?

Back 613

encompass a cascade of biochemical and cellular processes which are initiated by the primary process and which may cause ongoing cellular damage and even cell death

Front 614

What is the neurological level?

Back 614

The neurological level (motor or sensory) is defined as the lowest level that has completely normal motor and sensory function bilaterally

Front 615

What are the patterns of neurological injury?

Back 615

The following syndromes need to be recognised:
-Central cord syndrome-Usually a cervical injury causing UL>>LL weakness
-Anterior spinal artery syndrome-Variable loss of motor, pain and temp, with intact proprio
-Brown-Sequard syndrome-Ipsilat motor and proprio loss and contral pain and temp
-Complete versus incomplete injuries
-Conus injuries
-Cauda equina syndrome

Front 616

What are complete injuries?

Back 616

 no preservation of any motor/sensory function more than 3 segments below the level of the injury
 About 3% of patients with complete injuries on initial examination develop some recovery within 24 hours
 Poor prognosis for recovery

Front 617

What are Incomplete injuries?

Back 617

 Sensation (including proprioception) or voluntary movement in the lower limbs
 “sacral sparing”: sensation around the anus and buttocks or anal tone is spared

Front 618

What are stable injuries?

Back 618

 Spine can withstand physical loads
 No significant displacement or deformity to bone or soft tissue

Front 619

What are unstable injuries?

Back 619

 Spine may not be able to carry normal loads
 Most likely have significant deformity and pain
 Potential for catastrophic neurological injury

Front 620

What is the 3 column model (Denis)?

Back 620

 Used to grade thoracolumbar and cervical fractures
 Based on 3-column theory of the spine:
– Anterior = ALL and anterior 2/3 of vertebral body/disc
– Middle = posterior 1/3 of vertebral body/disc and PLL
– Posterior = pedicles, lamina, facets, post. Ligaments

Front 621

What is spinal shock?

Back 621

 Transient physiological disruption which leads to a hypotonic areflexic state
 Should not impair initial assessment as motor and sensory components only affects for <1 hr
 The higher the level of injury, and the more severe the SCI, the longer and more profound the spinal shock
 Different to neurogenic shock

Front 622

What are the expected outcomes of spinal cord injury?

Back 622

 Complete injuries rarely walk again
 Incomplete injuries may make a near normal recovery

Front 623

What is the clinical suspicion of SCI?

Back 623

 The following should be suspected of having a SCI until proven otherwise:
1. All victims of significant trauma
2. Trauma patients with LOC
3. Minor trauma patients with complaints referrable to the spine (neck or back pain or tenderness) or spinal cord (numbness or tingling in an extremity, weakness or paralysis)
4. Any patient with priapism or diaphragmatic breathing

Front 624

What is pre-hospital care for SCI?

Back 624

 At scene:
– Initial manual in-line immobilization
– A. Rigid hard collar
– B. Sandbags, straps and taping as required
– C. Spinal board
– D. Log rolls and spine lifts
 Helmet removed by 2 persons

Front 625

What are the key points of assessment for SCI?

Back 625

 Don’t confuse hypovolemic shock with neurogenic shock
 Be aware that other fractures may be present

Front 626

 Be aware of other injuries (e.g. abdomen) that may be masked

Back 626

 Don’t underestimate the respiratory status

Front 627

What are the goals of surgery?

Back 627

 Reduction / Realignment
 Decompression
 Stabilization

Front 628

What is the timing of decompression in cervical spine trauma?

Back 628

 Neurologically deteriorating patient
– urgent decompression warranted
 Neurologically stable patient
– controversial
– biological rationale for early intervention
– no compelling evidence exist from clinical human studies

Front 629

Define concussion?

Back 629

When the head is hit hard, the brain is damaged as it bounces, first hitting one side of the skull and then the other.
This may cause a CONCUSSION.

Front 630

What is a concussion?

Back 630

 Transient alteration in mental function due to angular rotation of brain structures
 No gross or microscopic changes
 LOC is typical
 CT and MR is normal

Front 631

Describe skull fractures.

Back 631

 Base of skull
 Linear (simple)
 compound
 depressed
– Epidural Hematoma
– Subdural Hematoma
– Intracerebral Hematoma

Front 632

Describe the occurrence of the different types of intracranial hematomas.

Back 632

 Extradural 16%
 Extradural & ICH 7%
 Subdural 22%
 Subdural and ICH 34%
 Intracerebral 20%

Front 633

Describe epidural hematoma.

Back 633

 generally younger age group (<5% over 50 years)
 M:F=4:1
 <10-27% have classical presentation
 Overall mortality 20-55% (higher in older series)
 Mortality is higher without lucid interval

Front 634

Describe acute subdural hematoma.

Back 634

 more lethal than EDH
 no “lucid interval”
 blood 2dry to:
 tearing of bridging veins
 parenchymal damage
 Needs craniotomy
 Mortality 50-90%
 If OT within 4 hrs: 30% mortality, otherwise 90% (“4 hour rule”)
 Underlying brain injury in addition to the clot

Front 635

Describe cerebral contusion.

Back 635

 Bruising of the brain
 Causes swelling
 May cause local dysfunction or pressure problems
 Typically frontal/temporal/occipital
 Contra-coup (counter-blow)

Front 636

Describe the assessment of head injuries.

Back 636

 Vital signs
 GCS
 Pupils
 Motor responses
-Glasgow Coma Scale
-Neurological Exam
-Localization Test

Front 637

What are the values of the Glasgow coma scale?

Back 637

Motor Exam
6- Follows commands
5- Localizes to axillary pinch
4- Withdrawal to nail bed pressure
3- Flexor to nail bed pressure (decorticate)
2- Extension to nail bed pressure (decerebrate)
1- Flaccid to nail bed pressure

Front 638

Describe the pupillary exam head injuries.

Back 638

 The initial pupil exam, with the GCS score establishes a neurological baseline
 The pupil exam in conjunction with the GCS score aids in determining treatment
 The pupillary exam should be performed:
– after resuscitation
– before administration of sedatives or paralytics
 Afferent: optic nerve
 Efferent: IIIrd CN palsy via midbrain

Front 639

Describe the results of the pupillary exam.

Back 639

 Pupil reactivity to light
– positive reaction > 1mm constriction
 Pupil asymmetry
– significant asymmetry > 1mm difference
 Fixed/Dilated Pupils
– pupils that are  4mm and react < 1mm

Front 640

What are some significant pupillary findings?

Back 640

-Pupil Asymmetry-Pupils that are greater than 1mm difference in size are considered asymmetric.
-Fixed & Dilated Pupils-Pupils that are greater than or equal to 4mm in diameter and constrict less than 1mm in reaction to bright, direct light are considered fixed and dilated.

Front 641

Describe the management of head injury.

Back 641

 ATLS guidelines
 Assessment / Treatment
– Airway
– Breathing
– Circulation
– Cervical Spine
– Disability
– Exposure

Front 642

What are the signs of cerebral herniation?

Back 642

In an unconscious and unresponsive patient:
 Patient with dilated and unreactive pupil(s)
 Patient with asymmetric pupils
 Patient non-responsive to painful stimuli
 Patient displaying extensor posturing

Front 643

What are the treatment of mild head injuries?

Back 643

 Majority do not require any specific treatment
 Duration of PTA guides severity of TBI for concussions etc.
 Reasons for admission and observation:
– patients with altered levels of consciousness at the time of evaluation
– focal neurological symptoms or signs
– open penetrating injuries
– a history of neurological deterioration
– confusion
– skull fracture
– difficulty in assessing the patient
– the absence of supervision by a responsible adult

Front 644

What is the guideline of intracranial pressure?

Back 644

Hypotension (SBP < 90 mm Hg) or hypoxia (apnea of cyanosis in the field or a PaO2 < 60 mm Hg) must be scrupulously avoided, if possible, or corrected immediately

Front 645

What are the complications of head injury?

Back 645

 Mental dysfunction
 Motor or other deficit
 Coma
 CSF leak- meningitis
 Taste disorder- common
 Memory problems
 Headaches
 Vertigo
 Deafness
 Concentration problems
 Hydrocephalus
 death

Front 646

What is a seizure?

Back 646

n Paroxysmal, excessive and disorderly discharging of neurons
n particular site of discharge in the brain determines clinical expression

Front 647

What are the Components of a seizure?

Back 647

n aura-earliest portion of seizure
n ictus- actual seizure
n post-ictal- immediately after seizure

Front 648

What is epilepsy?

Back 648

n Epilepsy is defined as a syndrome of recurrent seizures
– There are multiple classifications of epilepsy
– Epilepsy is not a benign disease
n SUDEP occurs in 0.35/1000 cases
n Psychosocial factors
n Cost of hospitalization, medications, lost work, etc
n 50% of epileptics continue to experience seizures despite treatment
n One seizure does not an epileptic make

Front 649

What are the different classifications of seizure?

Back 649

n Partial seizures
n Generalized seizures
– convulsive
– nonconvulsive
n Status Epilepticus
n Non-epileptic seizures

Front 650

What are the different types of generalized seizures?

Back 650

n Typical absense seizures (petit mal)
– atypical absense
n Myoclonic
n Clonic
n Tonic
n Tonic-clonic (grand mal)
n Atonic

Front 651

What are the epilepsy syndromes of adolescents?

Back 651

n Juvenile absence epilepsy
n Juvenile myoclonic epilepsy
n Epilepsy with TC upon awakening
n Benign partial seizures of adolescence
n Temporal lobe epilepsy
n Progressive myoclonic epilepsies
n Mitochondrial encephalopathies

Front 652

What are the causes of localization-related epilepsies?

Back 652

n Vascular-stroke, AVM,SAH,venous thrombosis, carotid dissection, SCA
n Infectious- meningitis, encephailits,abscess
n Tumor
n Degenerative- MS
n Traumatic
n Congenital

Front 653

What are some factors that identify epileptic syndromre?

Back 653

n Seizure type by history
n EEG
n Etiology
n Response to AEDs
n Inheritance
n Natural History

Front 654

What are some conditions that may be mistaken for seizures?

Back 654

n Syncope
n Non-epileptic seizures (pseudoseizures)
n Breath holding spells (children)
n Paroxysmal REM sleep behavior
n Panic attack

Front 655

What are some common causes of provoked seizures?

Back 655

n Massive sleep deprivation
n Excessive use of stimulants
n Withdrawal from sedatives or alcohol
n Substance abuse
n High Fever
n Hypoglycemia
n Electrolyte imbalance
n Hypoxia

Front 656

Describe the history of the event in evaluating single seizure history.

Back 656

– careful review of events days before sz
– presence of prodromal syndrome (aura)
– description of sz from witness
– post-ictal observations--time to recovery

Front 657

Describe the medical history of the event in evaluating single seizure history.

Back 657

– Febrile convulsions as child
– History of head trauma
– Cerebrovascular or Cardiovascular Disease
– Cancer
– Substance Abuse
– Infectious Disease

Front 658

Describe family history in evaluating single seizure history.

Back 658

– Febrile convulsions
– Epilepsy in siblings, parents, or close relatives
– History of other neurologic disorders

Front 659

Describe social history in evaluating single seizure history.

Back 659

– Travel
– Occupation

Front 660

Describe physical examination of single seizure examination.

Back 660

– Injury Pattern (tongue biting, burns, etc)
– Cardiovascular system
– Skin (neurofibromatosis, etc)

Front 661

Describe neuro examination of single seizure examination.

Back 661

– Focal post-ictal deficits
– Focal neuro deficits after recovery
– Neuropsychologic assessment

Front 662

Describe the lab workup for the evaluation of the single seizure.

Back 662

n Routine Labs
– Electrolytes, CBC, LFTs, glucose
– Tox screen
– ?Prolactin
n Structural Study
– MRI preferable
n EEG
n ?Lumbar Puncture

Front 663

When should a patient be treated after a single seizure?

Back 663

n Structural lesion
n Infection of CNS or meninges
n History of epilepsy in sibling
n History of childhood febrile seizures
n Significant head trauma
n Todd’s post-ictal paresis
n Status epilepticus at onset

Front 664

When should a patient not be treated after a single seizure?

Back 664

n Alcohol withdrawal
n Drug abuse
n Seizure from hypoglycemia or electrolyte imbalance
n provoked by excessive sleep deprivation
n immediate post-impact seizure

Front 665

Describe the recurrence risk after first unprovoked seizure.

Back 665

n Hauser et al,1990 --followed 208 patients for 5 years and found that the overall risk for a second seizure was 34% at five years.

Front 666

How are anti-epileptic drugs chosen?

Back 666

based on seizure type, groups include:
1. partial-simple, complex or secondarily generalized
2. absence
3. myoclonic
4. generalized tonic-clonic

Front 667

Describe the evaluation of recurrent seizure on monotherapy.

Back 667

n Rule Out:
– Non-compliance
– Inadequate dosing
– Infection
– Electrolyte disturbance
– Provocation (substance abuse, fever, sleep deprivation, stress, etc)
n If above ruled-out, consider second agent (or referral to neurologist)

Front 668

Describe vagus nerve stimulator.

Back 668

-VNS lead transmits signals from the generator to the vagal nerve
-generator is implanted under the skin in the upper left chest

Front 669

Describe the treatment of epilepsy in women in child-bearing years.

Back 669

n Daily supplementation of folic acid
n AEDs decrease effectiveness of oral contraceptives
n Oral contraceptives do not (usually) affect seizure threshold
n Menstrual cycle variation
– Estrogen is epileptogenic
– Progesterone is anti-epileptogenic
n Pregnancy Risk vs Benefit Analysis for continuing AEDs
n North American Registry for Epilepsy in Pregnancy

Front 670

Describe driving with epilepsy in Nevada.

Back 670

n Mandatory physician reporting to the DMV
– Nevada one of only six states with mandatory reporting
n Exceptions to mandatory loss of license:
– Breakthrough seizure caused by MD-directed change in medication
– Isolated seizure where additional seizures are unlikely
– Seizure related to temporary illness
– Established pattern of only nocturnal sz
– Established pattern of simple partial sz
– Patients are eligible to reapply for license after being seizure-free for 3 months

Front 671

Describe the epidemiology of brain tumors.

Back 671

-Varies with geographical location
USA 5-6 per 100,000
Kuwait 1 per 100,000
Iceland 10 per 100,000
-Lowest in Asians and highest in Caucasians
-Male:female ratio is 1.4:1

Front 672

Describe brain tumor mortality.

Back 672

• Second leading cause of neurologic death after stroke.
• Age
• Functional status

Front 673

What are the different types of brain tumors?

Back 673

• Tumor type dictates survival
– Nerve sheath
– Meningioma
– Ependymoma
– Oligodendroglioma
– Medulloblastoma
– Astrocytoma
– GBM

Front 674

Describe the symptoms of brain tumors.

Back 674

• Headache
• Seizure
• Mental change
• Hemiparesis
• Vomiting
• Dysphasia
• Impaired consciousness
• Visual failure

Front 675

Which headaches do you scan in fear of a brain tumor?

Back 675

• Headaches upon awakening
• Headaches that vary with position
• Worst headache of patient’s life
• Headaches accompanied by other neurologic signs or symptoms
• Headache which appears and won’t go away
• Severe headache without migraine characteristics

Front 676

What are the different types of intracranial CNS tumors?

Back 676

– Supratentorial, (70% adult)
• Astrocytoma
• GBM
• Metastasis
• Meningioma
– Infratentorial, (70% children)
• Medulloblastoma
• Astrocytoma
• 4th ventricle ependymoma

Front 677

What are the different types o intraspinal CNS tumors?

Back 677

– Extradural
• Epidural mets
• Bone tumors
– Intradural
• Intramedullary
– Ependmoma
– Astrocytoma)
• Extramedullary
– Schwannomas
– Meningioma

Front 678

What are the different classifications of cerebral gliomas?

Back 678

1. astrocytoma
2. oligodendroglioma
3. mixed neuronal and glial tumors
a. ganglioglioma
b. ganglioneuroma
c. central neurocytoma
d. dysembryoplastic neuroepithelial tumor (DNET)

Front 679

What are the different classifications of astrocytic tumors?

Back 679

1. astrocytoma-grade 1, pilocytic, giant cell
2. astrocytoma-grade 2, fibrillary, protoplasmic, gemistocytic
3. anaplastic astrocytoma-grade 3, very cellular and pleomorphic
4. glioblastoma multiforme-grade 4, endothelial proliferation and necrosis, multicentric glioma, gliomatosis cerebri

Front 680

Describe glioblastoma multiforme.

Back 680

• Age: 45-55
• Male:female 2:1
• 20% of all Intracranial tumors
• 50-55% 0f all cerebral gliomas
• Ring-like enhancement on MRI
• Butterfly when it crosses the corpus callosum
• Tx: Surgical resection, XRT,chemo
• Mean survival:
– 6 months without treatment
– 1 year with treatment

Front 681

Describe the different types of intraventricular tumors.

Back 681

1. neuroepithelial cyst
2. ependymoma
3. giant cell astrocytoma
4. central neurocytoma
5. choroid plexus papilloma
6. meningioma
7. ectopic pinealoma
8. epidermoid tumor
9. CSF seeding of tumor

Front 682

What some nerve sheath and meninges tumors?

Back 682

• Schwannoma
– Acoustic schwannomas most common
– Bilateral in NF2
• Neurofibroma
– NF1
• Meningioma
– 15% of all intracranial tumors
– 25% of all intraspinal tumors

Front 683

Describe metastatic tumors.

Back 683

• Most common infratentorial tumor in adults
• 80% are supratentorial
• Gray-white junction with vasogenic edema
• 50% appear solitary at presentation
• Leptomemingeal carcinomatosis
• Spinal cord compression

Front 684

What is multiple sclerosis?

Back 684

• Multiple Sclerosis- Scarred areas
• Lesions in the CNS
• Demyelination

Front 685

What is the pathology of MS?

Back 685

-Plaques- scars, lesions
-Areas of inflammation
-Infiltration of macrophages and T-cells
-Destruction of myelin

Front 686

What is the mechanism of pathology?

Back 686

destruction of myelin as well as destruction of axons

Front 687

Describe the etiology of MS.

Back 687

• Autoimmune disease
• Environmental
• Infectious
• Genetic

Front 688

Describe the epidemiology of MS.

Back 688

• Age of onset 20-40 yrs
• Most common neurological disease of young adults
• Female to male 2:1
• Genetic factors
– 1st degree relatives 20x risk
– Monozygotic twins 30% concordance
• Geographical distribution
– Associated with first 15 years

Front 689

Describe the clinical course of MS.

Back 689

• Extremely variable course among individuals
• Common symptoms include visual disturbances, vertigo, limb weakness, optic neuritis, numbness
• Fatigue
• Pain

Front 690

Describe the disease patterns in MS.

Back 690

• Relapsing-Remitting (RRMS) 75%
• Secondary Progressive (SPMS)
• Primary Progressive (PPMS) 10-15%
• Progressive-Relapsing (PRMS)

Front 691

What are the pathological patterns in MS?

Back 691

• Mayo Clinic- Brain biopsies
• 4 pattern types (not the same as clinical)
– Each patient has only one type
• May lead to specific treatments
• Early disease may be inflammatory and later may be degenerative

Front 692

How is MS diagnosed?

Back 692

• History & Physical
• Neurological exam- lesions separated by space and time
• MRI
• Spinal tap
• Evoked potentials

Front 693

What is the treatment for MS?

Back 693

• Management of acute attacks
• Management of symptoms
• Modification of disease course
• Improvement or maintenance of physical function
• Psychosocial support

Front 694

What is the general treatment for MS?

Back 694

• Exercise – aerobic
• Nutrition
• Rest / sleep
• Stress avoidance
• Heat avoidance
• Avoid infections- flu shots

Front 695

What is the treatment of disease course for MS?

Back 695

• Disease modifying agents
-Avonex - beta interferon
-Betaseron - beta interferon
-Copaxone – polypeptide
-Rebif- beta interferon
-Tysabri- monoclonal antibody
• Immunosupressant
-Novantrone (mitoxantrone)

Front 696

What are the treatments for progressive MS disease?

Back 696

– Steroids
– Chemotherapeutic agents
– Plasma exchange
– Radiation

Front 697

What are alternative treatments for MS?

Back 697

– Cranial sacral massage
– Bee venom
– Goats blood

Front 698

What is the future of MS treatment?

Back 698

• Research
– Repair- stem cells
– Genetics
– Immunology
• Testing
– Antibody testing
– Genetics
• Medicines
– HmgCoA reductase inhibitors
– Small molecule
– Biologics
– Numerous drugs in trials now – many are oral

Front 699

What can cause CNS infections?

Back 699

 Bacteria
 Viruses
 Fungus
 Parasites

Front 700

What are some routes of infection?

Back 700

 Hematogenous
 Abscess
 Respiratory
 GI/GU
 Venous spread
 Pericranial sites –sinuses, middle ear
 Less Common
 Penetrating trauma
 Entry through congenital defects

Front 701

What are the different types of infection?

Back 701

 Meningitis- meninges usually arachnoid
 Encephalitis- brain
 Myelitis- spinal cord

Front 702

When are CNS infections emergencies?

Back 702

 Brain and Spinal Cord do not repair well
 Brain is enclosed- increased intracranial pressure, untreated can lead to brain herniation- necrosis
 Can lead to sepsis

Front 703

What are the signs and symptoms of acute bacterial meningitis?

Back 703

 Signs & Symptoms
 Headache
 Nausea & vomiting
 Fever
 Meningismus
 Altered consciousness
 In children < 28days old , fever > 100.6 full septic work-up including lumbar puncture

Front 704

How is bacterial meningitis diagnosed?

Back 704

 History & Physical
 CT of Head to rule out space occupying lesion –if quick
 Lumbar puncture
 Blood cultures

Front 705

What are CSF findings in pyrogenic meningitis?

Back 705

pyrogenic meningitis can lead to neutrophils, elevated protein, DEC sugar, + gram stain

Front 706

What is the treatment for pyrogenic meningitis?

Back 706

 Antibiotics
 Hospitalization
 Steroids
 Supportive Care

Front 707

What is viral meningitis?

Back 707

 Headache
 Fever
 Viral Syndrome
 Meningismus

Front 708

What are CSF findings in granuloamtous and viral meningitis?

Back 708

lymphocytes, elevated protein, DEC sugar, negative gram stain

Front 709

What is the treatment for ganulomatous and viral meningitis?

Back 709

 Supportive Care
 Most cases resolve after 7-10 days
 Antivirals- for some cases

Front 710

What are the signs and symptoms of encephalitis?

Back 710

 Confusion
 Personality change
 Altered mental status
 Fever
 Seizures

Front 711

How is encephalitis diagnosed?

Back 711

 History and physical
 Brain imaging to rule out space occupying lesion
 Lumbar puncture
 Culture of CSF (some organisms)
 Antibody titers
 PCR of CSF for Herpes encephalitis
 Brain biopsy in exceptional cases

Front 712

What are the signs and symptoms of brain abscesses?

Back 712

 Headache
 Focal neurologic deficits
 Fever, chills and other signs of infection usually do not occur
 Papilledema (with increased ICP)
 Nausea, vomiting (with increased ICP)

Front 713

What is the treatment for brain abscesses?

Back 713

 Antibiotics
 Surgical drainage

Front 714

What are the indications for lumbar puncture?

Back 714

 Suspected cases of meningitis & encephelitis
 Diagnostic workup
 severe headaches
 MS
 Subarachnoid hemorrhage
 Treatment
 Pseudotumor Cerebri
 Increased ICP

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Describe the procedure of lumbar puncture.

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 Tell the patient what you are doing
 Mark site
 Sterile! Sterile! Sterile!
 Prepare wide area –Betadine or alcohol
 Drape
 Local anesthetic -lidocaine
 Introducer needle –direction
 Spinal needle with stylet
 Advance slightly cranial
 Usually feel “pop” of dura
 Measure pressure – fill tubes

Front 716

Describe CSF specimens.

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 Tube #1: glucose and protein
 Tube #2: cryptococcal antigen, Gram stain
 Tube #3: bacterial cultures
 Tube #4: cell count and differential

 About 1-2 cc/tube

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What are some possible complications of lumbar puncture?

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 Spinal Headache
 Nerve damage
 Back pain
 Infection

Front 718

What are some contraindications of lumbar puncture?

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 Patient refusal
 Skin infection or abscess
 Bleeding disorder