Neuroinfectious Diseases Exam 1 Flashcards
1
Q
What are 3 reasons that neuroanatomy is important?
A
- remains incredibly clinically relevant portion of anatomy
- necessary to interpret the neurologic and mental status of patients
- important for fundamental understanding of the brain’s functions
2
Q
what are the 2 main divisions of the nervous system
A
- CNS
- PNS
3
Q
what makes up the CNS?
A
- encased in bone: brain and spinal cord
4
Q
what is the brain
A
the central processing organ
5
Q
what is the spinal cord
A
the major conduit of information
6
Q
what is the PNS? How is it divided
A
everything outside of the CNS
- divided into the somatic and visceral PNS
7
Q
Somatic PNS
A
voluntary control
8
Q
Visceral PNS
A
involuntary or autonomous
9
Q
What are both the CNS and PNS made up of?
A
neural cells
10
Q
What are the 3 main regions that the brain can be divided into?
A
- cerebrum
- cerebellum
- brainstem
11
Q
Cerebrum
A
largest, and newest part of brain
12
Q
Cerebellum
A
- Involved in all voluntary functions
- smaller than cerebrum, but contains more than half of the total neurons in brain
13
Q
Brainstem
A
- Involved in all involuntary functions
- smallest, and oldest part of brain
- base where the cerebellum and cerebrum rest on
- connects the brain and spinal cord
14
Q
What are the 2 divisions of the cerebrum
A
left and right hemispheres
15
Q
what connects the 2 hemispheres
A
corpus callosum
16
Q
Cerebrum lateralization
A
idea that the 2 hemispheres of the brain are distinct in what they process with each side having specific specialties
17
Q
The sulci
A
the deep folds in the brain
18
Q
the gyri
A
the mountains in the brain
19
Q
what are the 4 main lobes of the cerebrum
A
- frontal lobe
- parietal lobe
- occipital lobe
- temporal lobe
20
Q
Frontal lobe function
A
responsible for attention, planning, and decision making (behavior)
21
Q
parietal lobe function
A
integrates information from the senses (orientation and cognition)
22
Q
occipital lobe function
A
responsible for vision (and perception based on visual cues)
23
Q
temporal lobe function
A
associated with language, memory, and emotion (specially based on sound cues)
24
Q
The 5 main segments of the spinal cord
A
- cervical cord
- thoracic cord
- lumbar cord
- sacral cord
- coccygeal cord
25
what grows faster, the vertebral column or the spinal cord?
the vertebral column
26
each segment of the spinal cord contains various pairs of..?
spinal nerves
27
what are the layers of protection of the CNS
1. skull and vertebral column
2. meninges
3. Cerebrospinal fluid (CSF)
28
how does the meninges protect CNS
- it encompasses both the brain and spinal cord
29
what are the layers of the meninges?
Dura mater (outermost)
arachnoid mater (middle)
pia mater (innermost)
- there is also the SLYM which is bw the arachnoid and pia mater
30
what divides the subarachnoid space into 2 functional spaces?
the SLYM
31
Function of SLYM
- forms a new anatomical barrier
- plays an active role in immune surveillance
- necessary for correct function of the glymphatic system
32
after a traumatic injury to the cerebellum, which of the following activities will most likely be affected?
a: establish a conversation over the phone
b) run a marathon
c) sing on a concert
D) playing chess
E) solving math equations
B. running a marathon because the cerebellum is in charge of voluntary movement which is really active when moving the body to make it run
33
Ventricles
Canals that connect CSF filled spaces
34
who first discovered ventricles
Hippocrates
35
who described morphology of ventricles
Leonardo Da Vinci
36
what are the 4 main ventricles
1. left lateral
2. right lateral
3. third ventricle
4. fourth ventricle
37
what connects the ventricles
connected by interventricular foramen (connect lateral ventricles to third ventricle) and cerebral aqueduct (connect third and fourth ventricles)
38
What is the spinal tap
a clinically important process used to diagnose neural disorders
- it takes a needle and injects it into the CSF to take a sample which is then used to diagnose
39
What is CSF
it is mostly water with some sugar and salts, it is an electrolyte, almost 100% p and cell free
- aka has no RBC
40
How does spinal tap help diagnose neural disorders?
the presence of p or cellular infiltrates is indicative of dysfunction
41
Hydrocephalus (from greek words "hydro" meaning water and "cephalus" meaning head) is a condition where there is excessive accumulation of fluid in brain. What would be a direct consequence of it?
a) the infant skull will expand to accommodate the buildup of water bc the sutures have not yet closed, resulting in a large head
b) excess water will flush out all the toxins from the brain, resulting in better functioning of neurons
c) can result in development of other mental diseases/disorders, such as Alzheimer's disease or Parkinson's
d) the meninges will withstand the intracranial pressure, redirecting the force towards the soft brain tissue, compensating for it and keeping its function.
a) the infant skull will expand to accommodate the buildup of water because the sutures have not yet closed, resulting in a large head
42
Grey vs white matter in CNS
in the brain, the grey matter is on the outside while the white is on the inside but the inverse is true on the spinal cord
43
post mortem brains are useful for
visual or manual inspection aka anatomical description
44
what are some functional brain imaging techniques
CT, MRI, and PET scans
45
CT scan
it distinguishes air, liquid, and bone filled areas
- skull appears white while parenchyma is grey and sinuses are black
46
MRI scan
distinguishes soft tissue
- white from grey matter
air and bone give no signal
- both appear black
47
PET scan
highlights areas of metabolic activity
bc it uses radioactive tracers, it is very quantitative w/ large dynamic range
48
Who injected melted wax into a brain to reveal the exact nature of the brain's ventricles?
Leonardo Da Vinci
49
The brain is involved in processing or directing all of the following except:
a) taste, vision, touch, smell and hearing
b) movement and response to stimuli
c) food degradation and absorption
d) learning, talking, emotions
C
50
The high degree of folding of the cerebral cortex creates more space for neurons, which is postulated to allow what of the following?
a) move and coordinate our limbs
b) coordinate and reasoning
c) to have at least nine senses
d) to multitask (like walk and talk at the same time)
B
51
Evolutionary speaking, what three parts of the brain can be put in order of appearance during evolution, starting with the ancient part first?
C. the brainstem -> the cerebellum -> the cerebrum
52
The brain is a __________ ball, with empty space inside filled with liquid
hollow
53
Many nerves come together to form nerve fibers, which can also come together to form thick bundles called nerve tracks. The largest of these is called the ____________________, which forms a bridge between the brain's_________________
corpus callosum; hemispheres
54
The spinal tap is a procedure possible because the _____________ grows faster than the ___________
vertebral column; spinal cord
55
What are the two functional units of the nervous system
1. nerve cells (neurons)
2. glia cells (neuroglia)
56
what are neurons, what is the function
basic units of nervous system
involved in acquisition, integration, and transmission of electrical signals
57
what are neuroglia and what is their function?
homeostasis-maintaining cells that support neurons and allow them to function optimally by performing a variety of functions
58
What is the basic structure of a neuron
1. dendrites
2. soma
3. axon
59
dendrites
branching extensions that collect information from other neurons
60
soma
the cell body, the core region of a neuron
61
axon
one root that transmits messages to other neurons
62
direction of flow of information in a neuron?
unidirectional
goes from dendrite to soma to axon to synapse to dendrite
63
what is the gap between neurons called
synapse
64
what carries signals between neurons
ions and molecules
65
what are the 4 types of axon connections to transmit info
1. axon-dendrite
2. axon-spine
3. axon-soma
4. axon-axon
66
what transmits signals across synaptic cleft
neurotransmitters
67
what triggers secretion in a neuron
action potential
68
what are the 2 main types of receptors that receive information from an axon?
ionotropic or metabotropic
69
what are the 4 types of morphology for the soma in a neuron?
1. unipolar
2. bipolar
3. multipolar
4. psuedounipolar
70
what are the 3 main types of information that neurons process
1. sensory
2. motor
3. interneuron
71
sensory neuron function
bring info to the CNS
72
motor neuron function
send signals from brain and spinal cord to muscle
73
interneuron function
associate sensory and motor activity in the central nervous system
74
what are the 3 zones of the macroanatomy of a neuron?
the input zone
conducting zone
output zone
75
what brain matter holds the conducting zone of the neuron
white matter
76
what are the 4 main types of neuroglia
1. astrocytes
2. oligodendrocytes
3. microglia
4. ependymal cells
77
what are the other specialized or ill-defined glia?
1. NG2 cells
2. radial glia
3. muller glia
4. bergmann glia
78
Based on your knowledge of the relationship bw micro and macro anatomy of the nervous system, which of the following is FALSE:
a) because the thick fibers in the brain (like corpus callosum) are myelinated, they appear as "white matter"
b) the grey matter and white matter localization (relative to each other) are the same between the brain and the spinal cord
c) the neurons in the brain cortex are specialized on integrating multiple signals, hence they have extensive branching and can process complex action potentials
d) the neuron's function will determine its structure (ex: number or length of processes)
B
79
Main 5 functions of Astrocytes
1. regulate neuronal communication (Synaptogenesis)
2. regulate blood brain barrier (BBB)
3. nutrients support to neurons
4. regulate signal transmission by interacting with nodes of Ranvier (space bw myelin sheets)
5. repair metabolic damage (caused by ROS; osmotic; pH)
80
what is the most abundant glia cell
astrocytes
81
what is the function of oligodendrocytes
these cells are in charge of myelination in CNS (like Schwann cells are in PNS)
they surround axons and produce myelin
82
what if function of NG2 cells
they act as multipotent precursors to other glia, but in particular to oligodendrocytes
83
what is the most proliferative (grow and increase in size most rapidly) cell in the CNS
oligodendrocytes
84
What causes myelinated axons to be faster than unmyelinated ones?
saltatory conduction produced due to nodes of Ranvier on myelinated sheaths
85
which cells are the immune cells of the CNS
microglia
86
where does microglia come from
originates in blood
- enter CNS during embryonic development
- are very long lived (varies depending on brain region)
87
What are the 3 ways that microglia are immune cells of CNS
travel through brain and spinal cord keeping it clean via:
- synaptic pruning
- removal of death cells
- remodel neuronal networks
88
location of ependymal cells
found in the walls of ventricles
89
function of Ependymal cells
- make and secrete CSF
- ciliated side creates flow of CSF
90
Which of the following would result in attenuation of the action potential?
a) a disease that cause all axons to enlarge (but keep concentration of cell components)
b) a disease that destroys myelin sheaths
c) a disorder that prevents production of neurotransmitters
d) a condition that restricts ion exchange to nodes of Ranvier
B
91
Which of the following statements is the most accurate description of neuroglia?
a) they all originate from the blood and then migrate to the brain
b) they are electrically non-excitable cells that support the function of the brain
c) they are the homeostasis- maintaining cells of the nervous system
d) is the collective name for all the cell types present in the brain and spinal cord
c
92
which of the following cells could be described as a stem cell?
a) oligodendrocytes
b) astroglia
c) NG2 cells
d) ependymal cells
C
93
What are the two broad types of receptors in a synapse?
ionotropic and metabotropic
94
How does a signal flow through the nervous system?
a) Dendrite > axon > soma > synapse > dendrite
b) Synapse > dendrite > soma > axon > synapse
c) Axon > soma > dendrite > synapse > axon
d) Soma > axon > synapse > axon > soma
B
95
What are examples of synapses?
a) Axon with dendrite
b) Axon with spine
c) Axon with axon
d) All of the above.
e) Only (a) and (b)
D
96
T or F: Microglia are the resident immune cells of the brain.
True
97
T or F: In the brain you can find these three types of cells: neurons, endothelial cells, and epithelial
cells.
True
98
T or F: Myelin is a fatty substance produced by oligodendrocytes in the central nervous system and by
Schwann cells in the peripheral nervous system.
True
99
T or F: The ‘all-or-nothing law’ of cellular excitation establishes that neurons can regulate the action
potentials.
False, neurons cannot control whether they fire or not
100
T or F: The special neurons of the cerebral cortex can process complex signals because they harbor
multiple axons.
False, all neurons only have 1 axon
101
A neuroglia with a characteristic star-like morphology?
astrocyte
102
Cells in charge of myelination in CNS are _____________ (similar to _________ cells in PNS)?
oligodendrocytes; Schwann
103
Pluripotent cells that give rise to other glia, in particular oligodendrocytes
NG2 cells
104
Epithelial cells that form the walls of the ventricles
ependymal cells
105
Based on morphology (physical form), neurons can be classified as __________,_________,__________, or __________
unipolar, bipolar, multipolar, or pseudounipolar
106
The ____________ are very long lived glia also involved in synaptic pruning and healing
microglia
107
What is unique about the blood in the brain ( 3 things)?
1. one of the highest metabolic demands in the body
2. unique blood makeup
3. require a tight control of water and ion concentrations
108
What metabolic demands does brain blood have? (3 things)
1. need lots of oxygen
2. need a constant carbon source
3. generate a lot of waste
109
what is the makeup of brain blood
- 55% water
- has lots of ions and molecs
110
what causes tight control of water and ion concentrations in brain blood?
- little spaces for liquid inside the head
- ionic strength of extracellular and intracellular milieu critical for action potentials
111
Functions of cerebral circulation (5 things)
- has to provide large volumes of blood
- has to provide a constant supply
- has to be insensitive to fluctuations in blood pressure
- work together with choroid plexus to generate CSF
- essential part of glymphatic system
111
functions of the BBB (5 things)
- allow uptake of glucose
- allow removal of waste
- allow gas exchange
- control cellular migration
- formidable barrier for pathogens
112
3 main types of vessels
1. arteries
2. veins
3. capillaries
113
flow of arteries vs veins
arteries come from heart and go to rest of body (in this case brain) while veins are on their way to the brain
114
What is the vasculature
the system of vessels that carry blood and lymph throughout the body
115
what is the vasculature made up of ?
endothelial cells that line the inside of all the vessels
116
what are the 3 types of endothelium
1. continuous
2. fenestrated
3. sinusoid (or discontinuous)
117
What type of vessels are seen in the CNS
continuous
118
what are the 4 large arteries that come directly from the aorta
1. left internal carotid
2. right internal carotid
3. left vertebral artery
4. right vertebral artery
119
how much of the brain blood supply comes from the carotids?
80%, the other 20% comes from the vertebral arteries
120
where does the spinal cord blood supply come from
all from vertebral arteries
121
Carotids mostly flow to what region of the brain?
mostly the cerebrum
122
the vertebral arteries mainly flow to what areas of the brain?
mostly to the cerebellum and brain stem
123
where does all the blood flow to the brain meet?
the circle of willis
124
what is the circle of willis
where the 3 next main arteries that supply blood to the rest of the brain are located
125
what are the 3 main arteries in the circle of willis
anterior, middle, and posterior cerebral arteries
126
what are the functions of the circle of willis
1. main collateral ensuring blood flow to brain
2. allow redistribution of blood if one or more of the arteries are occluded
3. low resistance (pressure), allows blood flow to go either way in the ring
127
what forms the second collateral system that ensures blood flow to the brain?
the pial network of vessels in the meninges
128
make up of the main arteries
- extracellular matric and nerve cells
- smooth muscle layers (up to 20)
- endothelial layer (contains dozens of ECs)
129
make up of pial arteries
same as main but has 3 smooth muscle layers
130
make up of intracerebral arteriole
- pericytes and astrocytic endfeet
- 1 layer of smooth muscle
131
make up of microcapillaries
- specialized ECs that DO NOT have smooth muscles
132
example of a microcapillary
the blood brain barrier
133
what are the 3 barriers of the CNS
1. BBB
2. Blood CSF
3. Blood meningeal
134
where is the BBB located
at the level of the microcapillaries
135
where is the Blood-CSF located
at the choroid plexus
136
where is the blood-meningeal located?
in the arachnoid space
137
where are there fenestrated endothelium in the brain?
- at the surface intracranial vessels (in the dura)
- at the choroid plexus vessels
138
how does blood drain from the blood
draining occurs from inside towards the surface and involves all major sinuses
139
where do all the sinuses join
join at the jugular
140
why is venous drainage important (3 reasons)
1. removes spent blood from brain, parenchyma, meninges, and eyes
2. removes CSF
3. removes waste
141
Where is the BBB present
in the capillary beds of the brain (microcapillaries)
142
The BBB is formed by: (5 things)
1. special endothelial cells known as BMECs
2. pericytes (type of mural cell)
3. astrocytes (their endfeet)
4. Basal (or basement) membrane
5. microglia (constantly surveying the microvessels for "insults")
143
what is the main component of the BBB
BMECs
144
what are the 4 functions of the BBB
1. control molecular traffic: CO2 and O2 permeable; lipid soluble permeable; small peptide permeable
2. ion homeostasis: anything ionic impermeable
3. high affinities for nutrients: active transport by protein transporters
4. control cellular traversal: immune surveillance w/ minimal inflammation
145
BMEC structure
- flatter and larger than systemic ECs
- vessel diameter is span by a single BMEC
- have tight junctions
- high number of mitochondria
146
function of BMECs
- restrict paracellular passage using TJ
- very low rates of transcytosis
- restrict transcellular passage
147
what regulates transcellular passage across BMECs
regulated by cellular transports, localized at specialized domains, apical or basal
148
Efflux transporters in BMECs, location and function
- on apical side
- bind lipophilic (lipid soluble) molecs inside the cells and transport them back into the blood
149
Influx transporters of BMECs, location and function
- on both sides (apical and basal)
- highly specific nutrient channels
150
what is required to power transporters of BMECs
lots of mitochondria
151
4 main types of cellular junctions
1. tight junctions (TJ)
2. Adherens junctions (AJ)
3. Desmosomes
4. Gap junctions
152
TJ are ______________________ barrier to ions, molecs, and cells
paracellular
153
what type of interactions can occur at TJ
homotypic or heterotypic interactions
154
examples of TJs
1. claudins
2. occludins
3. junctional adhesion molecs (JAMs)
155
describe TJs
interactions are so tight, that cellular traversal in the CNS occurs mainly by transcellular pores (imagine a donut)
156
Diff bw AJs and TJs in location
AJs are further away from the apical side compared to TJs
157
examples of AJs
Cadherins, in BMECs it is VE-cadherin
158
how are AJs regulated
Ca regulated
159
what are the major regulators of permeability
AJs
160
AJs link to the_______ _________ of the cell?
link to the actin cytoskeleton
161
What is the main type of endothelial cellular junction in the brain outside of the BBB
AJs
162
what are LAMs
low levels of leukocyte adhesion molecs
163
Where is velocity of blood flow greater? in systemic capillaries or microcapillaries
velocity is greater in microcapillaries than in system capillaries
164
What occurs when LAMs are upregulated during certain diseases?
TJs are disassembled and JAMs are exposed leading to cellular infiltration
165
Key properties of the BBB are due to features provided by?
BMECs (TJ, transporters, etc)
166
BMECs stands for
brain microvascular endothelial cells
167
where are pericytes located?
embedded in basal membrane of vasculature
168
general functions of pericytes
1. elasticity and rigidity (vessel diameter regulation)
2. angiogenesis, extracellular matrix production
169
what is angiogenesis
production of new blood vessels
170
functions of Pericytes in CNS
1. regulate immune cell infiltration
2. regulate permeability of BBB
3. inhibit features normal in the peripheral vasculature
171
function of Astrocytic endfeet in CNS? (4 things)
- astrocytes produce many factors that regulate BBB permeability
- increase TEER = decrease permeability
- regulate blood flow through secreted molecs that act on pericytes
- provide second layer of support (secrete extracellular matrix)
172
TEER
transendothelial electrical resistance
173
2 layers of basal membrane
1. vascular layer
2. parenchymal layers
174
function of basal membrane
- support function
- barrier function
175
what is needed to traverse the basal mem
enzymatic degradation
176
what surveys the basal membrane
microglia
177
what are the different permeabilities of the 3 barriers in the brain
1. BBB is impermeable
2. BCSFB is selectively impermeable
3. BMB is less impermeable
178
what other areas have permeable vessels and what barrier do they have
1. choroid plexus, pituitary gland, etc
2. each one has its own barrier
3. there is a need and mech to regulate it
179
what Diseases are associated with the BBB
1. stroke
2. multiple sclerosis
3. parkinson's disease
3. alzheimer's disease
5. epilepsy
6. TBIs
7. infectious diseases
180
what 4 pathologies are seen when diseases affect the BBB?
1. increased permeability
2. increased cellular infiltration
3. disruption of ion/pH homeostasis
4. disruption of neural function
181
Which of the following are functions carried out by the BBB?
a) Regulates the composition of the cerebrospinal fluid (CSF).
b) Controls the passage of bone-marrow stem cells into the brain.
c) Protects the brain from “foreign” substances in the blood by restricting their passage.
d) Provides the brain with a source of energy in the form of lipids.
C
182
The properties of the BBB are mostly due to the microvascular endothelial cells, but are
augmented and maintained by the action of which types of cells?
a) Astrocytes, microglia, and pericytes.
b) Microglia, muscle cells, and perivascular macrophages.
c) Astrocytes, pericytes, and perivascular macrophages.
d) Ependymal cells, microglia, and pericytes.
A
183
A scientist has discovered a drug to treat a specific type of brain infection. The drug is
ionized at the pH of human blood, which means that _____.
a) It will be actively absorbed by the BBB.
b) It will passively diffuse through the BBB.
c) It will not be pass through the BBB.
d) It will pass into the endothelial cells and remain trapped there.
C
184
There are 3 cellular barriers in the CNS:
a) The blood-CSF barrier, the meningeal barrier, and the BBB.
b) The choroid plexus, the dura mater, and the skull.
c) The dura mater, the meningeal barrier, and the BBB.
d) The blood-CSF barrier, the choroid plexus, and the arachnoid.
A
185
Which of the following are specialized features of the endothelial cells of the BBB?
a) Cellular junctions similar to that found in epithelial barriers.
b) Are highly ciliated.
c) A high concentration of plasma membrane transporters for lipids.
d) Fenestrations and ion-permeable pores.
A
186
The neurovascular unit includes: ____________, ____________, ____________, and
____________.
BMECs, pericyte, astrocyte endfeet, basal membrane, and microglia.
187
In the cerebral vasculature, there are two collaterals that ensure blood supply. These are
____________________ and ____________________.
circle of willis and pial network of vessels in meninges
188
The BMECs have many ________________ to be able to power all the transporters on their
surfaces.
mitochondria
189
____ side of the cell facing the basal membrane
(the solid extracellular matrix).
Basal side
190
____ can regulate the opening/closing of
cellular junctions.
Adherens junctions
191
____ protein plaques that link intermediate
filaments in the cell with the extracellular matrix.
Desmosomes
192
____ tunnels that traverses neighboring cells
allowing sharing of their cytoplasm.
Gap junctions
193
____ side of the cell facing the lumenal space
(i.e. ventricular space).
Apical Side
194
____ glue cells together to prevent leakage of
molecules between them.
Tight Junctions
195
what is the choroid plexus?
a highly vascularized structure that is the main gateway of immune cell entry into CNS, it contains the B-CSF barrier and is the main source of CSF
196
where is the choroid plexus located?
one in each ventricle (4 total)
197
how many stages in the structure of the choroid plexus
4 stages
198
Stage 1 of choroid plexi
- pseudostratified
- central nuclei
- microvilli (brush border)
- no villi
199
stage 2 of choroid plexi
- columnar epithelium
- apical nuclei
- microvilli (brush border)
- sparse primary villi (tissue folds)
200
stage 3 of choroid plexi structure
- cuboidal epithelium
- central or apical nuclei
- microvilli (brush border)
- more abundant primary villi (tissue folds)
201
Stage 4 of choroid plexi structure
- cuboidal epithelium
- basal nuclei
- microvilli (brush border)
- complex villi (multiple tissue folds)
202
flow of molecules in choroid plexi
travel through fenestrated capillary (exit through gaps there) and travel into interstitial space, from there, they must have an APC or be allowed in to cross into the choroidal epithelium
203
what is the flow of CSF in ventricular system
- unidirectional flow in ventricular system:
from lateral to interventricular foramina to third ventricle to cerebral aqueduct to fourth ventricle to central canal (into spinal cord) and median/lateral apertures (into subarachnoid spaces)
- multidirectional flow in the subarachnoid spaces
204
another name for subarachnoid spaces
perivascular spaces
205
Possible reasons that generate the CSF flow
1. beating cilia
2. pulsations on vessels from heartbeat
3. constant generation from one side and absorption on another
4. a combo of any of the above
206
what occurs if csf flow is interrupted?
brain will be damaged which has many causative reasons, most congenital
ex: infections or tumors
207
why can congenital problems in CSF flow can go unnoticed for years
because baby skulls are flexible and will not be immediately obvious, in these cases, it is treatable with a drainage tube
208
If CSF flow is interrupted as an adult, how can you treat this?
- it is very serious because by this time the skull is formed (no longer flexible) meaning that there is no room for expansion
- this interruption must be treated with surgery focusing on the cause not the consequence
209
How does CSF reabsorption occur?
1. travels from choroid plexus to the interventricular foramen
2. goes through the cerebral aqueduct, lateral aperture, fourth ventricle and its choroid plexus and exits through the median aperture
3. flow will then cross central canal of spinal cord and up the subarachnoid space
4. it then exits through the arachnoid villus into the superior sagittal sinus
210
what changes the valve opening in CSF reabsorption
the valve is the arachnoid villus that is controlled based on pressure
- low pressure causes valve to close and less CSF is absorbed
- high pressure causes valve to open and more CSF absorbed
211
The Choroid plexus can be involved in various pathologies, all of which can be grouped into 2 main categories: high volume and low volume of CSF. What causes each of these conditions?
1. conditions with high CSF volumes: BTI that damages valves, cancer of choroid plexi causing too much CSF, stroke, inflammation infection by fungi
2. conditions with low CSF volumes: death of ependymal cells, not enough water, autoimmune disease that attacks choroid plexus, CSF leak either due to trauma or medical intervention
212
2 main functions of Choroid plexus
1. CSF
2. immunosurveillance
213
what cells does the parenchyma not contain under normal conditions?
no t cells or b cells in parenchyma only microglia
214
how does choroid plexus immune surveillance in brain
they patrol the surfaces of the brain (yet low numbers)
215
most surveillance cells are ...?
resident effector cells such as perivascular macrophages
216
How do immune cells get into the CSF filled ventricle?
1. migrate across fenestrated endothelium into the stromal space
- this is where APCs and T cells are
2. they move along basal surface of ependymal cells
3. they cross into the CSF filled ventricle (either paracellularly or transcellularly)
217
what is the glymphatic system?
it is formed by the flow of the CSF and ISF through channels inside the brain and the channels are formed by astrocytes which actively pump water into parenchyma
218
function of glymphatic system
to remove waste and distribute nutrients
219
what drives the glymphatic system
driven by glia (astrocytes)
220
glymphatic system is similar to?
lymphatics
221
mice that are aquaporin deficient are similar to what disease?
develop a pathology similar to Alzheimer
222
When is the glymphatic system most active
when asleep
223
potential applications for glymphatic system
- gene therapy delivery
- drug targeting
- treatment for diseases related to molecule aggregates
224
what happens if you inject a dye into the blood?
the dye would stay in the blood
- does NOT travel into brain or CSF
225
what happens if you inject a dye into the CSF?
dye would travel into the brain and CSF area
226
The CSF flows in what direction?
a) Lateral ventricles > third ventricle > fourth ventricle > central canal
b) Interventricular foramina > third ventricle > fourth ventricle > cerebral aqueduct
c) Lateral ventricles > Interventricular foramina > cerebral aqueduct > third ventricle
d) Meninges > fourth ventricle > cerebral aqueduct > third ventricle
A
227
Which of the following is NOT a function of the CSF?
a) Decreases the effective weight of the brain by ~90%.
b) Cushions the brain and spinal cord from physical trauma, reducing the impact on the tissue.
c) Allows blood into the brain parenchyma to ensure good oxygenation.
d) Removes waste products from the CNS.
C
228
What would be an explanation for the Choroid plexus highly vascularized tissue?
a) It needs access to the blood to carry out its functions.
b) It generates more waste than normal epithelium, hence requires more blood flow.
c) Like the kidneys, it acts as a filter of the brain’s blood supply.
d) Like the liver, it secretes important molecules that need to be disseminated throughout the
body.
A
229
The Choroid plexus plays an important role in the brain’s immune system because
_____.
a) Is the primary site for red blood cell entry into the brain.
b) Is the entryway of immune cells into the perivascular spaces (and sub-arachnoid space).
c) Is thought to be the source of microglia as they differentiate from ependymal cells.
d) Ependymal cells are the resident immune cells of the brain.
B
230
Which of the following is NOT a feature of the glymphatic system?
a) Is driven by aquaporin channels on astrocytes
b) It distributes nutrients in the parenchyma of the brain
c) It is most active while awake
d) It removes wastes such as amyloid plaques.
C
231
T or F: The Choroid plexus is located within the ventricles and contains the B-CSFB.
True
232
T or F: The 4 Choroid plexi (one per ventricle) develop differently and carry out different functions
depending on location.
False, choroid plexi develop the same on each of the four ventricles and carry out same functions
233
T or F: Unlike the BBB, the vasculature in the choroid plexus contains sinusoid vessels.
False, vasculature of choroid plexus has fenestrated vessels and BBB has continuous
234
T or F: The glymphatic system is involved in both nutrient distribution and waste removal.
True
235
T or F: A defect in the function of the Choroid plexus will lead to disease, regardless of the magnitude of the defect as the brain will not be able to compensate
False, brain is able to compensate for these defects by making changes through reabsorption
236
what is the 2nd circulatory system that is essential for life?
the lymphatic system
237
function of lymphatic system is to support what 3 other systems in the body?
1. cardiovascular
2. immune
3. digestive
238
how does lymphatic system support the cardiovascular system
it unilaterally returns interstitial fluid (ISF) to the vascular system
239
how does the lymphatic system support the immune system?
it provides the environment that allows for initiation of an adaptive immune response
240
how does the lymphatic system support the digestive system
through the absorption of fat soluble vitamins and fatty substance from the GI tract
241
where is the lymphatic system found
throughout the body, it is parallel to blood vessels
242
which system is closed
blood circulation
243
what type of system is the lymphatics system
it is an open system
244
every blood capillary is interconnected with the lymphatics system except?
except the capillaries in the BBB
245
what is the fluid collected by the lymphatic vessels called?
lymph
246
what is lymph made up of?
- mostly derived from blood
- immune cells
- cholesterol, FA, and other fat and large products
- there is NO RBC in lymph
247
what is lymph from the GI tract called?
chyle
248
what is not present in lymph?
antibodies are too large
249
how are lymphatic vessels shaped?
they are blind ended, not fenestrated, just have endothelial flaps that interstitial fluid can enter through
250
Will the components of the lymph be the same regardless of the position in the body?
not all lymph is the same and the composition depends on where it comes from
251
what is constantly moving bw the blood and lymph
lymphocytes (t and b cells)
252
what constantly surveys tissues in lymphatic system
innate immune cells including macrophages and neutrophils
253
what does lymph collect from the blood and tissues
lymph collects all sorts of molecs including PAMPs and DAMPs
254
what are PAMPs
pathogen associated molecular patterns
255
what are DAMPs
danger associated molecular patterns
256
all the lymph, innate immune cells and molecules come together at what region
come together at lymph nodes
257
How does lymphocytes and lymph return to blood
via thoracic duct
258
where do naive lymphocytes enter the lymph nodes through?
enter lymph nodes from blood
259
how do antigens from sites of infection reach lymph nodes
via lymphatics
260
where does adaptive response start
at lymph nodes
261
why do activated lymphocytes return to blood
to target infection
262
why does lymphatic vessel enter through the opposite side of the blood circulation
the aorta has a lot of pressure and lymph does not have any, so if lymph valve is placed there, blood from aorta would invade into the lymph valve
263
why was immune privileged organ idea applied to the CNS
bc the CNS was traditionally thought to be devoid of lymphatics
264
location of CNS lymphatics
located in dura, next to major sinuses
265
make up of CNS lymphatics
intradural vessels that are leaky (fenestrated)
266
what type of molecules move through CNS lymphatics
cells and large molecs move bw layers
267
how is CSF transported within the large cavity of the subarachnoid space?
visualize CSF and immune cell movement within SAS
268
SLYM
sub-arachnoid lymphatic like membrane
269
SLYM features
divides SAS
phenotypically distinct from the dura, arachnoid and pia maters
acts as barrier for molecules that are 3kDA and bigger
270
what is the glymphatic lymphatic connection
it is an anatomically continuous and functionally related system that goes from glymphatic to lymphatic
271
glymphatic lymphatic connection function
glymphatic removes waste into veins and lymphatic removes fluid into lymph nodes
272
how does the CNS lymphatics survey immunology
- immune cells go in and out of brain through vasculature and lymphatics
- CSF/ISF constantly absorbed by lymphatics and monitored at cervical lymph nodes
- if antigens are found by immune cells, or antigens find their way into cervical lymph nodes, an immune response can be mounted
273
how does SLYM support role of dural lymphatics in CNS immunity
- it is closer to brain surfaces
- larger number of resident immune cells
- can regulate influx of immune cells from dura/skull bone marrow
274
SLYM can act like?
immune hubs
275
what role does CNS lymphatic system have in autoimmune disease
if they control immune responses in the brain, then controlling that gate could hold promise to treat autoimmune diseases
276
Which of the following is NOT a function of the lymphatic system?
a) Support the immune system by providing space for activation of lymphocytes.
b) Return excess protein and interstitial fluid (ISF) in the tissues back to the blood.
c) Allows absorption of nutrients passing through your intestines.
d) Removes CSF and ISF directly from the parenchyma of the brain and drains it into the gut
for disposal.
D
277
During a routine visit to your primary doctor, the physician finds enlarged lymph nodes
in your neck. What could be the cause of this enlargement?
a) You have an infection and immune cells in the node closest to the infection (your neck) are
actively dividing and specializing in killing the invader.
b) You have drink too much water causing the lymph node to inundate.
c) You have a defect in your skin.
d) The node is actively absorbing nutrients and lipids and have become swollen due to lack of
space.
A
278
Disorders like Alzheimer’s and Parkinson’s are thought to be a consequence of the accumulation of misfolded proteins in the brain. Which of the following statements could
be correct?
a) The glymphatic system is not working correctly, resulting in accumulation of these proteins.
b) The lymphatic system is not working correctly, resulting in accumulation of these proteins.
c) The vasculature in the brain is not working correctly, resulting in accumulation of these
proteins.
d) The meninges are not working correctly, resulting in accumulation of these proteins.
A
279
Which of the following is thought to be correct about the SLYM?
a) Is similar in structure and composition to the other meningeal layers.
b) Can organize the CSF in the SAS.
c) Is not a barrier (i.e. molecules can freely pass through it).
d) Is made up entirely of immune cells.
B
280
Which of the following statements best describes the neurolymphatic system?
a) Is a unique blind-ended unidirectional, absorptive and transport system that penetrates deep
into the brain tissues.
b) It consists of a multitude of lymphatic vessels all over the brain that drain directly into the
thymus.
c) It is present throughout the meninges and constantly scan the CSF and ISF for foreign
compounds.
d) It only scans, and survey, the CSF for foreign particles and does not have access to the
parenchyma of the brain, hence this area cannot be monitored.
C
281
T or F: Lymph from anywhere in your body will at least be filtered by one lymph node prior to return to the
blood.
True
282
T or F: The CSF/ISF flow is the common link between the glymphatic and lymphatic systems.
True
283
T or F: Lymph contains water, proteins, immune cells, and red blood cells.
false, lymph does not have RBC
284
T or F: The location of the CNS lymphatics vessels (i.e. in the dura mater rather than in the brain parenchyma) may explain the evidence previously used to state the immune-privileged organ hypothesis.
True
285
T or F: The lymphatic vessels are blind ended and as such, can allow easy flow of large molecules and cells.
True
286
why are cancers so hard to treat
- side effect of the brain barriers
- cancers are not inflammatory
- steal nutrients and blood away from normal cells
287
what does increased lymphatics result in
increased number of t cells and surveillance
288
what promotes lymphogenesis
VEGF-C
289
what results in destruction of a tumor
combinatorial therapy
290
how long is BBB
thousands of miles of blood vessels
291
what does the BBB allow to cross
glucose, oxygen and other nutrients
- prevents most toxins and infectious agents from coming in
292
2 main types of immune system responses
innate or adaptive
293
what is the time, effector cells and mechanism used during an innate immune response
innate is immediate bc it is the 1st/2nd line of defense, it uses physical (and chem) barriers; phagocytes (macrophages, etc) as effector cells and has a nonspecific mechanism against all invaders
294
what is the time, effector cells and mechanism used during an adaptive immune response
an adaptive immune response takes time bc it is reinforcements, the last line of defense (>48 hrs to 1 to 2 wks), uses humoral (antibodies) and cellular (cytotoxic lymphocytes) effector cells, and uses a specific mechanism against each antigen, provides memory (immunity)
295
what is another way that immune system response can be classified
afferent and efferent branches of immune system
296
what is an immune response
the body's response to antigens
- sneezing, coughing, inflammation, etc
297
what is inflammation
movement of immune cells into an area
- field of battle, needs to be balanced
298
what is the damage response framework
- outcome depends on host response
- outcomes can move along the parabola
- host and pathogen factors can affect parabola
299
what is unique about the CNS (4 things)
1. rigid layers covering CNS
2. immune responses have to be controlled
3. historically thought to be "immune privileged" (IP)
4. like other organs, must have a way to defend itself from infections
300
what does immune privileged mean
the absence or a greatly diminished immune system
301
how can IP be a double edge sword
it prevents complete clearance of pathogens and provides protection to tumors
302
5 pieces of evidence FOR immune privilege
1. tissues implanted on brain parenchyma are not rejected
2. bacterial/viral antigens injected on brain parenchyma failed to evoke an adaptive response
3. at steady state, very low levels of lymphocytes seen on perivascular spaces (none in parenchyma)
4. absence of lymphatic vessels
5. presence of BBB
303
5 pieces of evidence AGAINST immune privilege
1. tissue are rejected if transplanted into ventricles
2. PAMPs on CSF filled compartments elicit rapid infiltration of immune cells (inflammation-meningitis)
3. large number of phagocytes (antigen presenting cells APCs) are constantly present on CSF filled compartments (and the parenchyma has microglia)
4. discovery of meningeal lymphatic vessels
5. Lymphocytes can be forced to cross BBB (artificial solution, but biologically possible)
304
what does each CNS barrier establish
compartments with diff relationships with the immune system
305
what are the 3 CNS barriers established compartments
1. meninges
2. ventricles
3. parenchyma
306
Meninges connections
incoming and outgoing connections through the vasculature and lymphatics
307
ventricles connections
incoming and outgoing connections through choroid plexus
308
parenchyma connection
no connection, only resident cells, microglia
309
what removes antigens from parenchyma into CSF spaces
glymphatics
310
what kind of molecules does glymphatics remove
small/soluble antigens
311
The meninges is bathed by?
both CNS fluids, CSF and ISF
312
what does the meninges contain?
lymphatic vessels which allow for sampling of fluids and potential immune hub
313
what is the meninges connected to
cervical lymph nodes
314
function of the meninges
exhibit rapid inflammatory responses
315
where do activated T cells come from and where do they enter
activated T cells can enter SAS from arachnoid or dural veins
316
what does choroid plexi generate
the CSF
317
what kind of vessels are located in the ventricles
fenestrated vessels which allow easy access for immune cells to choroid plexus stromal space
318
what is the imp of a large number of resident APCs present in the ventricles
helps sample CSF (and ISF that drains there)
319
function of ventricle connections
exhibit rapid inflammatory responses
320
where do t cells cross into after activation in choroid plexi
cross into ventricles
321
what is the brain parenchyma protected by
by bbb, no direct entry
322
what does ISF do in parenchyma
ISF washes parenchyma and drains into veins and SAS (limited to small, soluble antigens)
323
T or F: there is direct access to lymph nodes from the brain parenchyma
false
324
what are epiplexus cells
intraventricular macrophages
325
at steady state in the parenchyma, there are no _________?
no lymphocytes
326
presence of APCs in perivascular spaces flanking BBB?
low number of APCs present
327
what is cut off from adaptive immune response
the brain parenchyma
328
why is the brain parenchyma being cut off from adaptive immune response significant?
because it means it cannot get waste out/bring nutrients in, which is where the glymphatic system comes in
329
what can cross the BBB into brain parenchyma
monocytes and other innate immune cells (APCs) can cross
- perivascular macrophages or dendritic cells
lymphocytes can cross into perivascular space of venules during surveillance (which is infrequent) and when signaled by endothelia
330
what is needed in order to cross into brain parenchyma
need to be reactivated by APCs
331
Over the last decade, a lot has become clear about the CNS's immunology, and explains some of the observations leading to the IP hypothesis. How would you explain these observations?
1. transplantation of a tumor, or foreign tissue, into the brain parenchyma is not ejected
2. transplantation of the same foreign tissue peripherally or into the ventricles elicited immediate rejection
3. soluble components from the parenchyma and the CSF were found in the cervical nodes
4. there are no professional antigen presenting cells in the brain parenchyma (microglia have low MHC expression) to activate T cells
...
332
4 ways of immune surveillance of the CNS
1. blood derived APCs patrol CNS covering tissues (but dont enter brain parenchyma
- meninges, ventricles
2. in homeostasis, soluble CNS antigens are shed into CSF via the glymphatics
3. Antigens can be picked up by APCs or by lymphatics (then traffic to the cervical lymph nodes for activation)
4. non activated/activated lymphocytes return back to bloodstream and back to CNS
333
steps (10 total) walking through an immune response example
1. virus gain access to parenchyma
2. virus recognized by microglia
3. microglia is activated
4. cytokines released
5. endothelia activated
6. cytokines released and JAMs/LAMs are upregulated
7. circulating lymphocytes enter the brain
8. infected cells are killed (and viruses with them)
9. lymphocytes become anti-inflammatory
10. signaling ends
334
what are regulatory T cells
cells that suppress and regulate the function of other immune cells
335
what are the two classes of Regulatory T cells
1. natural
2. adaptive
336
natural regulatory T cells
created in the thymus
337
adaptive regulatory T cells
formed by differentiation in the affected tissue
338
what cells are not present in the brain
no T cells in the brain, so these are adaptive regulatory t cells
339
what happens to t cells after virus/infection is defeated in the brain
they undergo apoptosis
340
8 steps of an immune response when dealing with an autoimmune disease
1. the own proteins cause microglia to activate
2. cytokines are released
3. incoming lymphocytes are activated against the same antigen
4. activated APCs go to lymph node which activate more lymphocytes
5. more lymphocytes are recruited
6. constant presence of antigens inhibits anti-inflammatory response
7. BBB collapses causing more infiltration
8. neurodegeneration ensues
341
Which of the following ideas was consistent with the “immune privilege” hypothesis?
a. The BBB prevented entry of immune cells into the parenchyma of the brain.
b. The lack of conventional lymphatic organs in the brain.
c. The lack of an immune response towards the injection of antigens directly into the ventricles.
d. All of the above.
e. (a) and (b).
f. (a) and (c).
E
342
Which of the following observations questioned the “immune privileged” status of the brain?
a. The constant presence of lymphocytes (albeit at low levels) in the CSF-filled compartments.
b. That nonself-tissue transplanted into ventricles is rejected.
c. That a substantial amount of the CSF drains into cervical lymph nodes.
d. All of the above.
e. (a) and (b).
f. (a) and (c).
D
343
Under healthy conditions, T cells rarely cross into the brain parenchyma. When they do, they cross-
downstream BBB, in the postcapillary venules. Which of the following is the correct sequence of events?
a. Cross the vascular endothelia, reactivation in perivascular space, cross the glia limitans.
b. Cross the vascular endothelia, cross the glia limitans, reactivation in the brain parenchyma.
c. Cross the glia limitans, reactivation in the blood, cross the vascular endothelia.
d. Cross the fenestrated vascular endothelia, reactivation in the perivascular space, cross the
ependymal cell monolayer.
A
344
Various features that explain the uniqueness of the neuroimmune system are?
a. Rigid layers preventing swelling.
b. Presence of BBB controlling migration of immune cells.
c. Absence of traditional lymphatics directly innervating the brain parenchyma.
d. All of the above.
e. (a) and (b) only.
D
345
Because the brain’s lymphatics are restricted to its surface, how do they still sample the parenchyma for
the presence of antigens?
a. Through T cells that constantly go inside and scan the brain parenchyma.
b. Through microglia, which when activated (by antigens) migrate out of the parenchyma and into the
lymphatics.
c. Through the glymphatic system, which removes waste (and antigens) from the parenchyma into the
SAS, where is now available to be sampled by the lymphatics.
d. Through arteries and veins that run parallel to the lymphatics and interexchange solutes (and
antigens).
C
346
Inflammation plays various important roles in an organism. These are?
a. Killing of pathogens.
b. Healing of tissues.
c. Removal of wastes and foreign bodies.
d. All of the above.
e. (a) and (b) only.
D
347
What will happen if T cells cross into perivascular spaces and fail to be activated by Antigen-presenting
cells there?
a. Nothing, they will just scan the area and if nothing is found, head back into the circulation or are
removed via CSF-drainage pathways.
b. They turn into Tregs and then undergo apoptosis.
c. They will immediately cross the glia limitans into the brain.
d. They will destroy the astrocyte’s endfoot, generating a hole in the glia limitans.
A
348
Which of the following are instances that highlight drawbacks of the neuroimmune system?
a. The parenchyma of the brain can serve as a safe haven for tumors and encapsulated (large
enclosures) pathogens.
b. The CSF-filled spaces do not have access to lymphatics.
c. The ventricles are surrounded by BBB, preventing easy access of immune cells.
d. The neuroanatomy of the CNS both prevent foreign particles entry but also CNS-specific antigens
from exiting into the peripheral circulation.
A
349
Which of the following BEST describe the brain’s immune defenses?
a. The three cellular barriers (BBB, BCSFB, and BMB).
b. The BBB, microglia, and all the perivascular antigen-presenting cells (such as epiplexus cells).
c. The meninges, the CSF, and the skull.
d. The lymphatic and glymphatic systems.
B
350
The importance of Treg cells in the brain’s immune system is best depicted by which statement?
a. They promote infection clearance by expressing highly inflammatory markers that aid on pathogen
killing.
b. They regulate the immune response and coordinate the shift from inflammatory to anti-
inflammatory (healing).
c. Whenever cytotoxic T cells enter the brain they are turned into Tregs by the CNS environment,
ensuring that there are never inflammatory cells inside the brain.
d. They can respond to neurotransmitters like serotonin, which allow them to respond and follow
brain’s signals.
B
351
T or F: The different brain barriers define compartments in the CNS that differ functionally in their communication
with the immune system.
true
352
T or F: The CNS parenchyma is completely cut-off from the immune system, while the perivascular compartments
(including ventricles) have active immune systems.
False, the parenchyma is indirectly connected to immune system via the glymphatic system, also it has microglia
353
T or F: The brain’s ventricular and subarachnoid spaces exhibit the same immune privilege as the brain parenchyma.
False, CSF filled spaces have more access to the immune system compared to the parenchyma
354
T or F: Antigen-presenting cells in the SAS access the lymph nodes through dural lymphatics and come back to the brain through the same lymphatic vessels.
False, Lymphatic system is unidirectional so the APCs have to circulate back through the blood
355
T or F: An innate immune response will take between 1 and 2 weeks to develop - a clear example of that is the
COVID19 vaccine that takes 14 days to show protection.
false, an innate immune response is immediate while an adaptive takes time up to 1 to 2 wks
356
what is disease of the NS caused by
infectious agents, not necessarily living organisms
357
meninges nomenclature
meningitis
358
brain parenchyma nomenclature
encephalitis
359
spinal cord nomenclature
myelitis
360
focal contained infections
abscess or cysts
361
3 entry routes of virus into CNS
1. through a cellular monolayer (endothelium or epithelium)
2. through contiguous tissue
3. through nerve endings
362
how does a virus enter through a cellular monolayer into CNS (3 ways)
entry occurs at brain's capillaries and venules or at choroid plexi
1. transcellular route
2. trojan horse (infected leukocyte)
3. paracellular route (TJ broken)
363
what kind of invader enters CNS through contiguous tissue
mostly parasites and large pathogens (certain bacteria as well)
364
what invader enter through nerve endings
common for viruses, who can hijack secreted vesicles in synapses
365
6 symptoms associated with meningeal involvement
1. headache
2. fever
3. nausea
4. vomiting
5. neck pain (stiff neck)
6. reflex impairment
366
what are all the meningeal involvement symptoms related to
all related to increased intracranial pressure
367
how does CSF analysis differ if there is meningeal involvement
- high number of leukocytes, mainly polymorphonucleated cells
- high protein
- very low glucose
- high lactate
all related to pathogen's metabolism on the CSF
368
what are the 6 parenchymal involvement symptoms
1. headache
2. fever
3. impairment of senses (go blind, deaf)
4. impairment of consciousness
5. psychological changes
6. focal neurologic deficits
symptoms related to area of brain affected
369
how does the csf analysis differ with parenchymal involvement
- high number of leukocytes, mainly mononucleated cells
- high protein
- normal glucose
- normal to high lactate
presence of pathogen can usually be seen in brain scans
370
5 spinal cord involvement symptoms
1. back pain
2. muscle pain
3. partial paralysis
4. lower limbs paralysis
5. motor movement impairment
all related to interruption of comms bw CNS and PNS
371
how does CSF analysis differ with spinal cord involvement
- inflammatory markers
- immune cell pop depends on pathogen
- normal glu
- normal protein
aka not useful for determining pathogen
372
what study is conducted to determine pathogen is involved in spinal cord
neuroimaging must be performed, almost always in conjunction with meningitis or encephalitis
