Week 1 Lectures Flashcards
1
Q
It is composed of two layers of dense collagenous connective tissue with large venous sinuses formed where the various leaves of the mater come together
A
Dura
2
Q
A thin membrane containing a mixture of fibroblasts and arachnoidal cells, also known as meningothelial cells, and forms a continuous sheet subjacent to the dura and, in most places, joined to it to form one physically continuous tissue.
A
Arachnoid
3
Q
It anchors delicate strands of the arachnoid trabeculae, which connect the arachnoid to it.
A
Pia
4
Q
Subdural space
A
Normally the arachnoid matter is adherent to the dura. However, unlike the tight adherence between the inner table of the skull and the dura (only disrupted by high pressure such as arterial flow from a traumatized middle meningeal artery), this interface is more readily disrupted by minor injuries. Typically trauma results in tearing of the bridging veins that traverse this space as they pass between the cortical surface and the overlying dura resulting in the accumulation of blood in the subdural space (subdural hematoma).
5
Q
Subarachnoid space
A
an actual (not potential) cavity between the arachnoid mater and the pia mater, which contains vascular structures and CSF.
6
Q
Virchow Robin space
A
Since the pia mater is tightly attached to the brain and follows the vessels into the brain parenchyma, so does the subarachnoid space, creating the Virchow Robin spaces that surround vessels within the brain.
7
Q
Dural sinuses
A
In specific locations, the dural leaflets form the draining structures named dural sinuses.
8
Q
Dural sinuses are penetrated by ________ whose function is:
A
arachnoid villi (or arachnoid granulations); structures that conduct CSF back into the circulation
9
Q
T/F Arachnoidal cells are found distributed throughout the arachnoid membrane, but are most concentrated over the arachnoid villi.
A
T
10
Q
____________ have a distinctive histologic appearance, forming small multicellular clusters with prominent whorls and occasional ________ bodies
A
arachnoidal cells and psammoma bodies –> oval nuclei with fine, even dispersed chromatin and occasional pseudo-inclusions
11
Q
Arachnoidal cells are thought to be the basis for a slow growing tumor seen in older adults called _______.
A
meningioma
12
Q
T/F Normally clear, the arachnoid may become opacified with age due to thickening from the deposition of collagen in the subarachnoid space.
A
T –> opacification of the leptomeninges
13
Q
3 components of a neuron
A
- dendrites – multiple elongated processes specialized in receiving stimuli
- perikaryon (soma or cell body) – trophic center, i.e. center of nutrition, support and supply, also receptive to stimuli
- axon – single process specialized in generating or conducting nerve impulses. Axons end in specialized terminal arborizations, each branch of which terminates on the next cells in dilatations called boutons, which form part of the synapse.
14
Q
T/F most neurons have a prominent nucleolus.
A
T –> finely dispersed chromatin in nucleus too
15
Q
T/F Axons have nissl and dendrites don’t.
A
F –> axons don’t have nissl, dendrites do.
16
Q
T/F RER projects into axons.
A
F
17
Q
Astrocytes (A) and oligodendrocytes (O) are commonly referred to as _______ cells.
A
glial –> common precursors but different functions in CNS
18
Q
_______ are located in both gray and white matter and have long processes that are rarely visible as they merge into a feltwork of axons and dendrites called _______.
A
astrocytes and neuropil
19
Q
Bare nuclei appearance
A
astrocytes
20
Q
White matter vs. Gray matter astrocytes
A
In the gray matter astrocytes have numerous short highly branched processes (protoplasmic astrocytes). In the white matter astrocytes tend to have fewer and relatively straighter processes (fibrous astrocytes)
21
Q
Protoplasmic astrocytes
A
Gray matter
22
Q
Fibrous astrocytes
A
White matter
23
Q
Astrocyte function
A
extend numerous fine foot processes towards both the pial surface, around the basement membrane of blood vessels, and the non-synaptic regions of neurons. Astrocytes thus have an important structural role, as well as functional significance as mediators of metabolic exchange between neurons and blood
24
Q
Astrocytes contain an abundant amount of an intermediate filament known as __________ which can be used to highlight the presence of these fine processes, as well as to confirm the astrocytic nature of particular glial cells.
A
GFAP: glial fibrillary acidic protein
25
, these cells can only be identified histologically by their dense darkly stained nuclei and lack of conspicuous cytoplasm.
oligodendrocytes
26
___ are the predominant type of glial cell in the white matter
oligodendrocytes
27
T/F Likeastrocytes, there is no immunohistochemical stain (like GFAP) that can be used in tissue sections for ready identification of these cells.
F
28
In the gray matter oligodendroglial cells are often found in small groups of 2-3 cells in close proximity to neurons in a process called ______.
satellitosis
29
T/F A single oligodendrocyte can contribute to the myelination of up to 50 axons that may belong to the same or different fiber tracts.
T
30
The cytoplasm of the oligodendroglial cell is packed with _____, which makes sense for a cell type that makes lots of glycolipid membrane material
Golgi
31
The ______ lines the ventricles of the brain and the central canal of the spinal cord.
ependyma
32
Ependymal cell appearance
cuboidal with elongated nuclei, microvilli (thought to be involved in absorptive and secretory activity) and cilia (may be involved in propulsion of CSF through the ventricular system). Like other epithelial cells in the body, they are bound together by junctional complexes at their luminal surfaces. However, they do not rest upon a basement membrane. Instead, the base of ependymal cells breaks up into fine branches that interdigitate with an underlying layer of astrocytic processes. Specialized ependymal cells have elongated processes that extend to the subependymal vasculature, thus linking the ventricular, vascular and intraparenchymal compartments of the CSF. A similar pattern may be observed in tumors derived from ependyma (ependymoma) that often have prominent perivascular processes.
33
T/F Ependyma has no basement membrane.
T
34
Projections of vascular stroma derived from the meninges are covered with a low cuboidal epithelium that secretes _____.
CSF
35
_______ cells have numerous long microvilli with only a few cilia. They also have many mitochondria, large Golgi complexes and basal nuclei, which is consistent with their secretory activity.
Choroid plexus -->lateral ventricles and fourth ventricle
36
Cells found in layers of neocortex
1. a relatively acellular outer molecular layer,
2. external granular layer comprised of small round darkly staining neurons
3. external pyramidal layer comprised of larger triangular shaped neurons
4. internal granular layer
5. internal pyramidal layer
6. a polymorphous or multiform layer with a mixed populations of neurons, including large pyramidal type cells.
37
pyramidal cells give rise to ________ that point upwards towards the pial surface, and axons that are the efferent output of the neocortex which project downwards towards the ____________.
apical dendrites and subcortical white matter
38
large pyramidal cells are the efferent output of the neocortex and are located primarily in layers ______
3 and 5 --> external and internal pyramidal
39
. For example, the pyramidal cells of layers 3 and 5 are very large (Betz cells) in the primary __________cortex.
motor (precentral)
40
_______ cortex has small pyramidal cell layers but markedly expanded granular cell layers.
the primary sensory (postcentral)
41
Ammon's horn
hippocampus proper
42
three-layered cortex that connects the hippocampus to the parahippocampal gyrus
subiculum
43
Sommer Sector
CA1 --> most sensitive to various insults including ischemia, seizures, and degenerative changes from Alzheimer's
44
Each cerebellar _____ is comprised of a relatively hypocellular molecular layer (ML) that contains the complex dendritic processes of ______ cells
folia and purkinje
45
the greatest number of cerebellar neurons are actually contained in the densely packed _______.
granular layer (GL)
46
What cells are associated with: acute ischemic injury, chronic cell loss, and inclusions
neurons
47
What cells are associated with: reactive gliosis
glial cells
48
What cells are associated with: microglia and inflammatory infiltrates
inflammatory cells
49
"Red" neuron
cells that have experience irreversible ischemic injury. They are characterized by a shrunken cell body, intense cytoplasmic eosinophilia with complete loss of Nissl basophilia. They can be seen about 12-24 hours after the ischemic insult. The nucleus is frequently darkly stained without an evident nucleolus.
50
Red neurons can be seen about _____ hours after ischemic injury.
12-24 hours
51
Which regions of the brain are more vulnerable to ischemic injury?
the pyramidal neurons of the CA1 region in Ammon’s horn (hippocampus) and the Purkinje cells of the cerebellum
52
One of the most common subcellular alterations in neurons is the accumulation of _______, especially in large/small motorneurons of the spinal cord/brainstem/cortex.
lipofuscin in large motorneurons of the spinal cord
53
lipofuscin
This is a normal age-related process. Oxidized fatty acids from cell membrane breakdown accumulate as a fine light brownish retractile material, typically located along the perikaryal edge.
54
neuromelanin
by-product of neurotransmitter synthesis in these catecholaminergic neurons.
55
3 catecholaminergic areas of neurons that produce neuromelanin
These include the substantia nigra of the midbrain, locus ceruleus of the rostral pons and the dorsal motor nucleus of the vagus.
56
T/F Viral infections can lead to abnormal inclusions
T --> CMV (nuclear, cytoplasmic), herpes (nuclear), rabies (cytoplasmic)
57
T/F Many neurodegenerative disorders are associated with neuronal inclusions
T --> neurofibrillary tangles in AD, Lewy bodies in Parkinson's
58
______ are the main effector of reaction to injury in the CNS: through both hypertrophy and hyperplasia they cause ______, a common denominator for diverse causes of injury.
astrocytes cause gliosis
59
_______ react to injury by hyperplasia and by developing elongated nuclei and increased elongated cytoplasmic processes
microglia
60
Microglial nodules are aggregates of microglial cells that are often seen in some inflammatory conditions including _______.
viral encephalitis
61
5 most common routes of access to the CNS (by infections)
hematogenous spread, local extension (paranasal sinuses, middle ear), retrograde PNS transport, direct implantation (trauma, surgery)
62
T/F Virulence and tropism of certain organisms for neural and glial elements determines “homing” to the nervous system.
T
63
Spread of infection into layers of the dura mater
Pachymeningitis
64
Inflammation of the pia and arachnoid
Meningitis/Leptomeningitis
65
Inflammation (usually viral) of the brain parenchyma
| with mononuclear cells
Encephalitis
66
Inflammation (usually bacterial) of the brain parenchyma
| with neutrophils
Cerebritis
67
Inflammation of the spinal cord
Myelitis
68
Inflammation of spinal gray matter
Poliomyelitis
69
Inflammation of the dorsal root ganglia
Ganglionitis
70
Inflammation of the intradural spinal nerve roots
Radiculitis
71
Immune response associated with: Acute (bacterial) meningitis, cerebritis, abscess
Neutrophils (acute inflammation)
72
Immune response associated with: Chronic (“aseptic” viral) meningitis, encephalitis
Mononuclear cells (lymphocytes and plasma cells, chronic inflammation)
73
Immune response associated with: Micobacteria, spirochetes, fungi, parasites
Granulomatous inflammation
74
Immune response associated with: Viral encephalitis
Microglial nodules
75
T/F Bone, dura mater, arachnoid and pia mater delineate four compartments that tend to inhibit the spread of infection from one compartment to another
T
76
Most common area of bacterial CNS infection
Subarachnoid space --> meningitis/leptomeningitis
77
Epidemics of bacterial meningitis are common/rare and almost always associated with ______.
rare and Neisseria meningitidis.
78
Long term complications of bacterial meningitis
hydrocephalus due to leptomeningeal scarring blocking basal cisterns and arachnoid granulations and hearing loss
79
3 bacteria that cause the majority of bacterial meningitis.
S. pneumoniae, N. meningiditis and H. influenzae
80
Which age of patients are affected by: Group B Streptococcus, Escherichia coli, Listeria monocytogenes
neonates
81
Which age of patients are affected by: Streptococcus pneumoniae, Listeria monocytogenes
Adults >60 years and immunosuppressed
82
Which age of patients are affected by: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae
Children and Adults (6 mos to 60 years)
83
Macroscopic findings of bacterial meningitis
purulent exudate, opacification of leptomeninges
84
bacteria causing basal exudate in bacterial meningitis
H. Influenza
85
bacteria causing convexity exudate in bacterial meningitis
S. Pneumoniae
86
Microscopic findings of bacterial meningitis
neutrophils in leptomeningeal space, pia effective barrier to parenchymal spread, occasional cerebritis when infection crosses parenchyma
87
____are focal, destructive lesions (occasionally multifocal) of the brain parenchyma due to necrosis mediated by acute inflammation in response to bacterial infection.
Abscesses
88
2 sources of abscess forming CNS infections
Local (sinusitis otitis, mastoiditis) or hematogenous (septic emboli or cyanotic congenital cardiac disease-PFO)
89
Most common bacteria in abscess formation
S. aureus, Streptococci, often polymicrobial
90
T/F Bacterial endocarditis can cause
infectious emboli to travel to the brain
and cause abscesses
T
91
T/F Mass effect from a CNS abscess can cause herniation.
T
92
T/F abscesses in the CNS have surrounding fibrotic capsules.
T
93
4 features of early abscess formation
vascular congestion, early necrosis, edema and initiation of inflammation --> neutrophils
94
After approximately ______, neovascularization and collagen fibers start to create the abscess capsule that will eventually isolate the area of necrosis (eventually a cystic cavity) from the surrounding preserved parenchyma.
10 days
95
Features of late abscess formation
neutrophil debris and fibroblastic collagenous capsule
96
Typically, tuberculous meningitis involves the ____ aspect of the brain and presents with cranial nerve involvement
basal
97
CSF findings of TB meningitis
lymphocytosis, hypoglycemia, increase in protein
98
Acid fast stain
identify filamentous mycobacteria like TB
99
Which condition? chronic basal meningitis with associated obliterative endarteritis. Perivascular inflammatory infiltrate, rich in plasma cells and lymphocytes. Cerebral gummas (mass lesions) may also occur.
Meningovascular neurosyphilis
100
Which condition?invasion of the brain by Treponema pallidum. Inflammatory lesions associated with parenchymal damage in the cerebral cortex with loss of neurons, proliferations of microglia (rod cells), gliosis, and iron deposits. The spirochetes can, at times, be demonstrated in tissue sections.
Paretic neurosyphilis
101
Which condition? damage by the spirochetes to the sensory nerves in the dorsal roots and posterior columns. Organisms are not demonstrable in the cord lesions.
Tabes dorsalis
102
T/F In neurosyphilis, CNS is affected in the primary stage
F --> tertiary stage
103
Stage at which chancres form
primary syphilis
104
Stage of neurosyphilis with hematogenous spread, generalized lymphadenopathy, maculopapular rash, condyloma lata, mucous patches
secondary syphilis
105
Which organism causes lymphocytic meningitis, cranial nerve palsies, and polyradiculitis, and occurs several months after a skin rash known as erythema chronicum migrans?
Borrellia burgdorferi --> Lyme
106
Viral Inflammation restricted to the meninges
aseptic meningitis
107
Viral disease restricted to the grey matter
polioencephalitis, poliomyelitis
108
Viral disease of both grey and white matter
panencephalitis, panmyelitis
109
Viral disease of white matter
leukoencephalitis
110
What kind of viral meningitis? enterovirus
aseptic meningitis
111
What kind of viral meningitis? poliovirus, coxsackie, arbovirus, echovirus, tick-borne, rabies
polioenceph/myelitis
112
What kind of viral meningitis? HSV, HIV
panenceph/myelitis
113
What kind of viral meningitis? JC, PML, HIV
leukoencephalitis
114
T/F Viral meningitis is generally less severe than bacterial meningitis.
T
115
One form of recurrent aseptic meningitis ______ that was previously regarded as non-infective has been linked to infection with herpes simplex virus (HSV), especially HSV-2.
Mollaret's
116
What kind of viral meningitis? acute infection of meninges + lymphocytes in CSF,
aseptic meningitis
117
T/F Survivors of viral CNS infections involving the parenchyma can subsequently develop permanent neurological disease.
T
118
Which of the following are seasonal in nature? Arbovirus, HSV
Arbovirus Acute Viral Encephalitis
119
Most common cause of epidemic encephalitis.
Arbovirus (arthropod borne) --> birds, horses, small mammals, arthropods --> incidental/terminal hosts in humans
120
T/F The majority of human arbovirus infections are asymptomatic or may result in a nonspecific flu-like syndrome.
T
121
Site of arbovirus replication in humans
The virus replicates at the site of host inoculation and then spreads to regional lymph nodes and other lymphoreticular tissues (primary viremia) where it proliferates before disseminating hematogenously (secondary viremia) to systemic tissues, including, in some cases, the CNS.
122
General pathologic features of acute viral encephalitis
perivascular lymphocytic infiltrate, microglial nodules (gray or white matter + rod cells, macrophages, lymphocytes), neuronophagia, intranuclear cytoplasmic inclusions, gliosis
123
Bilateral, asymmetrical, hemorrhagic necrosis of temporal lobes is classical in _____ encephalitis.
HSV (but diff dx includes infarction and contusion) --> temporal involvement = seizure
124
_____ is the most common cause of acute necrotizing encephalitis in immunocompetent individuals.
HSV1 (sometimes CMV or VZV)
125
The initial HSV1 infection involves the _____
oropharyngeal mucosa
126
The putative routes of HSV1 CNS infection are
Centripetal spread of virus along olfactory nerve fibers and tracts, and reactivation of latent virus in the trigeminal ganglia
127
_____ virus replicates within skeletal muscle at the site of inoculation before being taken up by axons and transported centripetally to the CNS.
Rabies
128
Negri bodies are the hallmark of _____
rabies --->sharply delineated round to oval eosinophilic inclusions in neuronal cytoplasm
129
3 sites for negri bodies
Purkinje cells, hyppocampal pyramidal neurons, cortical neurons and brain stem nuclei
130
Which polio vaccine can revert to wildtype through back mutation?
live attenuated oral vaccine can revert and cause paralytic disease
131
Features of acute poliomyelitis
intense chronic perivascular inflammation of parenchyma and meninges, microglial nodules and neuronophagia, blood vessel congestion and possible hemorrhage
132
Diffuse encephalitis with space occupying lesions, septic infarcts, leptomeningitis, and hemorrhage are associated with _____
fungal infection
133
____ fungus often affects ACA, MCA territories causing early hemorrhagic infarcts and late abscesses
aspergillosis --> feature of chronic infection (from direct spread vs. hematogenous)
134
Grocott silver stain demonstrates thin filamentous fungal forms with branching in _____
aspergillosis
135
_____ usually starts with nasal or unilateral facial swelling and hyperemia.
Rhinocerebral mucormycosis with focal ulceration and necrosis of skin/mucosa --> The infection extends rapidly into the orbit, producing unilateral ophthalmoplegia, proptosis, edema of the lids, corneal edema, and blindness in some cases
136
2 classical presentations of mucormycosis
diabetic ketoacidosis, rhinocerebral disease
137
Hyphae are nonseptate in _____
mucor
138
Hyphae are wider in aspergillus/mucor
mucor
139
_____, has been isolated from fresh water, soil, sewage, heating, ventilation and air conditioning units, dental units, gastrointestinal washings, and dust and is a cause of meningoencephalitis.
Naegleria fowleri --> infection from swimming in fresh water at high temperature --> nasal cavity--> CNS
140
Which organism causes Fulminant, acute meningoencephalitis with cerebral swelling and hemorrhagic necrosis frontal lobes and olfactory bulbs ?
Naegleria fowleri
141
Most common helminthic CNS disease
cysticercosis
142
Cysticercosis is caused by _______
Taenia solium
143
______ cause of CNS infection is associated with epilepsy.
cysticercosis
144
Clinical features of cysticercosis
Manifestations can include focal and generalized seizures, papilledema, headache, vomiting and ataxia (which may be intermittent), vertigo produced by abrupt movements of the head, focal motor and sensory deficits, dementia, acute hydrocephalus due to obstruction of the ventricular system, and occasionally, sudden death.
145
T/F cysts formed in cysticercosis result in robust inflammatory responses.
F --> almost non response --> Shortly after the cysticerci die, the cysts are surrounded by neutrophils, lymphocytes, macrophages, foreign body giant cells, and eosinophils and then enclosed by a zone of granulation tissue, which eventually produces a dense collagenous capsule and eventually some of the cysts become calcified.
146
Most common cause of fungal meningitis
Cryptococcus neoformans
147
T/F Cryptococcomas (Cryptococcal abscesses) are much less common than cryptococcal meningitis and usually occur in patients who are not immunocompromised.
T
148
T/F in cryptococcus is usually pulmonary with subsequent hematogenous spread to the CNS.
T --> The pulmonary lesions have often resolved before the neurologic disease manifests.
149
Which organism is visible in India Ink?
Cryptococcus
150
Collections of _______ produce gelatinous pseudocystic dilations of Virchow – Robin spaces (“bubbles”) with little surrounding inflammation or gliosis
Cryptococcus
151
_______ is an opportunistic infection common in the setting of HIV caused by the protozoan, an obligate intracellular parasite with a propensity to infect the nervous system. The definitive hosts for this parasite are domestic cats and other feline species.
Toxoplasmosis
152
T/F In toxoplasmosis, symptomatic neurologic disease is unless associated with depression of cell-mediated immunity, particularly in AIDS, and is probably due to reactivation of dormant infection.
T
153
Which organism? Most common pattern is brain abscesses, presenting as multiple ring-enhancing lesions
Toxoplasma gondii
154
Which organism? Free tachyzoites and encysted bradyzoites may be found at the periphery of centrally necrotic lesions.
Toxoplasma gondii
155
3 areas affected by HIV encephalitis
Involves subcortical white matter, basal ganglia and brainstem
156
Which condition? Widespread low-grade inflammation with perivascular and parenchymal lymphocytes and microglial nodules, multinucleated giant cells, and leukoencephalopathy
HIV encephalitis
157
T/F In the CNS, HIV infects mainly microglial cells or macrophages.
T
158
Which organism has a tropism for oligodendroglia?
JC virus/polyoma
159
Which organism? Ill-defined demyelinating lesions, lipid-laden macrophages, intranuclear viral inclusions, bizarre atypic astrocytes.
JC virus/polyoma
160
glass nuclei are associated with _____
JC virus/polyoma
161
T/F concussion is equivalent to mild TBI
T
162
mTBI are due to ______
mild axonal injury
163
T/F Genetic risk factors for concussion are the strongest factor
T
164
Inertial loading is due to hit/rotation of the head due to _____ of axons called _____
rotation and tensile elongation of axons called viscoelasticity
165
Neuropathology of inertial loading
diffuse axonal injury and swelling of white matter, disconnection, variscose-like veins: 1. bulb evolution, 2. axonal swelling evolution
166
A spirochete like axons suggest _____ damage
initial mechanical damage
167
Microtubule catastrophe
during trauma, secondary chemical damage results in destruction of microtubueles
168
Axonal varicosities are due to damage of microtubules at single/multiple sites
multiple
169
The gold standard for diagnosing tbi is _____
amyloid protein
170
____ inhibits relaxation of undulations along axons post-injury by stabilizing microtubules.
Taxol -->stabilize microtubules by reducing relaxation and degeneration of microtubules in axons
171
Calcium influx due to increasing axonal strain is a result of _____ channels
Sodium--> inactivation gate -->unremitting entry of sodium into cell --> reversal of sodium/calcium exchanger = massive calcium influx
172
Can block calcium influx with TTX or ______ inhibitors.
protease inhibition of calpain (which proteolyzes the inactivation gate
173
Period of vulnerability
another mild injury is thought to trigger a greatly exaggerated response --
> repetitive mTBI
174
Repetitive mTBI results in exaggerated responses due to ______ sodium channels
hyperexpressed --> restoring axonal function may involve increasing # of channels --> NaChO
175
Immediate loss of consciousness and coma following brain trauma is due to ______.
DAI
176
______ is the current standard for non-invasively evaluating DAI
diffusion tensor imaging
177
T/F TBI is the highest epigenetic risk factor for developing AD-like dementia
T
178
The hallmark pathologies of AD, _____ are also found in CTE
amyloid plaques and neurofibrillary tangles
179
T/F mTBI can result in CTE
F --> moderate to severe or repetitive TBI
180
T/F In AD, amyloid is secreted intracellularly.
F --> extracellularly resulting in neuritic or diffuse plaques extracellularly
181
Abnormal hyperphosphorylated intra-neuronal accumulation of tau is called _____
neurofibrillary tangles
182
T/F axonal disconnection is permanent
T
183
T/F CNS tumors are classically classified by morphologic appearance including constituent cell type and tissue pattern
T
184
7 major histopathological categories of CNS tumors
neuroepithelial, cranial and spinal, meninges, lymphomas and hematopoietic neoplasms, germ cell, sellar, metastatic
185
Tumors of neuroepithelial tissue
astrocytomas, oligodendromas, ependyomas, embryonal tumors, neurocytomas (neurons), mixed neuronal-glial tumors
186
Most frequent primary CNS tumors are ____
neurepithelial origin
187
Astrocytoma categories
diffuse, infiltrating and relatively circumscribed
188
Diffuse, infiltrating astrocytoma
diffuse astrocytoma (II), anaplastic astrocytoma (III), glioblastoma (IV)
189
Relatively circumscribed astrocytomas are grade _____
I or II --> pilocytic, pleomorphic, subendymal giant cell
190
Grade II astrocytomas are diffuse/circumscribed and are characterized by _____
diffuse --> atypia no mitoses
191
Grade III Anaplastic astrocytomas are characterized by _______
atypia with mitoses
192
Grade IV glioblastomas are characterized by _____
atypia, mitoses, and vascular proliferation/necrosis
193
Glioblastomas are more common in old/young people
older --> higher grades are more common in older people
194
T/F diffuse astrocytomas are encapsulated.
F --> poorly defined
195
Which tumor? Elongated, irregular, angulated, hypochromatic nuclei in a meshwork of fibrilllary processes and no mitoses.
diffuse fibrillary astrocytoma --> grade II
196
Which tumor? Plump cells with glassy pink cytoplasm.
Diffuse astrocytoma, gemistocytic variant --> Grade II
197
Which tumor? Foci of increased cell density, hyperchromatism, and pleomorphism with mitotic figures.
Anaplastic astrocytoma --> Grade III
198
Which tumor? Necrosis, high cellularity, mitoses, and variable vascular supply with both glomeruloid tufts (neovascularization) and vessel death.
Glioblastoma --> Grade IV
199
Two types of GBM
primary --> EGFR and secondary --> IDH1/IDH2 and P53
200
Astrocytomas have a propensity for anaplastic transformation of diffuse Grade II to ____ or _____.
grade III anaplastic or grade IV GBM
201
T/F Neoplastic progression is associated with sequential acquisition of multiple genetic abnormalities.
T
202
BRAF/KIAA tandem duplications are associated with _____
pilocytic astrocytoma --> children and young adults
203
Which tumor? Well demarcated, solid, cystic lesion with rosenthal fibers, biphasic architecture with compact and spongy patterns and eosinophilic granular bodies//no mitoses or necrosis.
pilocytic astrocytoma
204
T/F In oligodendrogliomas, the neoplastic cells maintain certain features of normal oligodendroglial cells which form and support the myelin sheath in the CNS.
T
205
Which tumor? Well differentiated, infiltrating tumor, expanding gyri and deep white matter, fried egg appearance, chicken wire capillaries.
Oligodendroglioma
206
Most common genetic alteration in oligodendroglioma.
1p/19q --> genetically favorable for chemo/radiotherapy (grade II or III but no IV)
207
T/F rosettes and canals are found in the majority of ependyomas.
F
208
Which tumor? neoplastic cells clustered around blood vessels producing pseudorosettes due to perivascular arrangement of elongated cytoplasmic processes of neoplastic cells
Ependymoma
209
Which grade IV tumors are predominant in children?
Embryonal tumors like medulloblastoma, supratentorial PNET, AT/RT, and medulloepithelioma
210
Which tumor? high-grade cerebellar vermal tumor with extension to the 4th ventricle and opacification of the SA (sugar icing) with CSF dissemination//well circumscribed, gray/pink, gelatinous, limited necrosis//ovoid nuclei, highly packed cells with frequent mitoses
medulloblastoma
211
Some medulloblastomas are considered to originate from ____ neurons that produce the external granule layer.
Granule neurons
212
T/F homor wright rosettes are present in 40% of medulloblastomas and are regarded as signs of neuronal differentiation.
T
213
3 groups of cranial and paraspinal nerves?
schwannomas (neurilemmomas), neurofibromas, malignant peripheral nerve sheath tumors
214
Which tumor? slowly growing neoplasms of schwanna cells with effects on CNS, especially CN 8
Schwannoma --> cerebellar pontine angle
215
Patients with NF2 may have _____ acoustic/vestibular schwannoma
bilateral --> neurofibromatosis type 2
216
Which tumor? dermal nodular lesion of skin or intraneural, solitary, or plexiform neoplasm.
Neurofibroma
217
The presence of multiple neurofibromas is usually seen with _____
neurofibromatosis type 1
218
Which tumor? arise from meningothelial cells of leptomeninges with increased inceidence with age and associated with females//composed of whorls and cords of neoplastic cells and identified by EMA.
Meningiomas (ofen with NF2)
219
Which tumor? numerous compact whorls with psammoma bodies.
Psammomatous meningioma
220
The most common primary sites for metastic CNS tumors are ____
lung, breast, skin, kidney, colon
221
T/F Metastatic tumors are 50% likely to be solitary.
T
222
T/F Gliomas and embryonal tumors occur more frequently in males
T
223
T/F Meningiomas preferentially affect females
T
224
T/F Most primary brain tumors are sporadic and of unknown origin
T
225
T/F More than 5% of brain tumors are associated with heriditary syndromes that predispose to neoplasia.
F <5%
226
Neurofibromatosis Type 1 is associated with 4 tumors:
neurofibroma, malignant nerve sheath tumor, optic nerve astrocytoma, meningioma
227
Neurofibromatosis type 2 is associated with 3 tumors:
schwannoma, meningioma, ependymoma
228
Tuberous sclerosis is associated with 1 tumor
subependymal giant cell astrocytoma
229
T/F X-irradiation increases risk of brain tumors
T --> meningiomas and astrocytomas or other tumors of neurepithelial origin in children treated b/c of ALL
230
Headache (postural, nocturnal, early morning), vomiting, papilledema, and clouding of consciousness/coma are signs of _____
increased intracranial pressure
231
Which kind of herniation? cingulate below falx cerebri
subfalcine
232
Which kind of herniation? parahippocampal gyrus of medial temporal lobe across tentorium cerebelli
transtentorial
233
Which kind of herniation? anteromedial part of temporal lobe
uncal
234
Which kind of herniation? diencephalon through tentorium cerebelli
bilateral/central/diencephalic
235
Which kind of herniation? tonsils
tonsillar
236
Which kind of herniation? cerebellum through tentorium
superior cerebellar
237
secondary hemorrhages due to transtentorial herniation is called ____
duret hemorrhage
238
Which nerve is compressed against petrous ligament?
abducent
239
Which nerve is implicated in uncal herniation?
Oculomotor
240
What structure is compressed against the tentorium with ipsilateral hemiparesis?
cerebral peduncle
241
Which familial syndrome is related to CN 8?
NF2
242
Complete turnover of CSF occurs every _____ hours
5-7
243
Adults produce ____ ml/day CSF
500
244
Approximate CSF volume in ventricles is ____ and in SA space is ____
30 and 120 ml
245
Choroid plexus
located in ventricles, specialized ependymal cells (cuboidal glial cells)
246
Blood to the choroid plexus is provided by _____ arteries
anterior/posterior choroidal arteries
247
Stages of CSF production
1. ultrafiltration of plasma across fenestrated capillaries, 2. secretion/transport of components into ventricle from choroid epithelia (isoosmotic)
248
T/F Capillary ultrafiltrate is outside the blood-brain barrier
T --> choroid plexus epithelia employ tight junctions to create a barrier against free diffusion
249
CSF has high/low protein
low
250
CSF has high/low amino acids vs. plasma
low
251
CSF has high/low K+ vs. plasma
low
252
CSF is absorbed into the venous blood supply of the_______
superior sagittal sinus and spinal veins
253
Small arachnoid evaginations are called
villi
254
Large arachnoid evaginations are called
granulations
255
T/F CSF can enter venous blood but venous blood can't enter CSF
T --> one way valve
256
What mechanism is likely to be implicated in absorption of CSF?
transcytosis via large fluid containing vacuoles
257
T/F Since there is no lymphatic system in the brain, CSF serves an excretory waste function.
T
258
2 routes into CNS and function
blood brain barrier, regulated at capillaries --> O2, CO2, glucose; blood-CSF barrier, regulated at choroid plexus --> Ca2+ influx
259
3 reasons for integrity of BBB
1. tight junctions between non-fenestrated capillaries, 2. thick basement membrane, 3. astrocyte endfoot "insulation"
260
Which molecules are excluded from the BBB?
large, charged molecules
261
Which molecules cross the BBB more readily?
uncharged and lipid soluble molecules
262
T/F BBB is permeable to water
T
263
Circumventricular organs
areas around ventricles that lack definitive BBB b/c have leaky capillaries --> part of neuroendocrine control system for monitoring temp/plasma concentration and for hormone release
264
Collect the CSF specimen from the patient in the __________ position
lateral recumbent --> CSF pressure changes with posture
265
In LP, needle insertion occurs at what level?
L3-L5
266
Normal adult opening pressure
90-200 mm water
267
Normal pediatric opening pressure
10-100 mm water
268
contraindication to LP
raised intracranial pressure could lead to cerebral herniation
269
Most common complication of LP
headache
270
What's in the CSF? Cloudy
elevated WBC
271
What's in the CSF? Bloody
RBC due to SAH
272
What's in the CSF? Yellow/Xanthochromic
orange from carotene ingestion, brown due to metastatic melanoma
273
What's in the CSF? Viscous
metastatic mucinous adenocarcinoma
274
Normal CSF glucose
60 mg/dL
275
What's in the CSF? Low glucose
neutrophils reliant on anaerobic glycolysis --> low glucose due to infection
276
Normal CSF protein
30 mg/DL
277
T/F for detecting Cryptococcus, India ink has a lower sensitivity than latex agglutination antigen assay
T
278
5 classical symptoms of meningitis
fever, headache, AMS, stiff neck, photophobia
279
What kind of meningitis? elevated opening pressure, elevated WBC, most neutrophils, high protein
bacterial
280
What kind of meningitis? normal opening pressure, mainly lymphocytes, normal glucose and protein
viral
281
What kind of meningitis? variable opening pressure, mostly lymphocytes, elevated protein
fungal
282
Liptotechoic acid
S. pneumoniae --> cell wall protein that links to PAF to enter CNS
283
Layers of head
scalp, periosteum/outer and inner table of skull, potential epidural space, dura, potential subdural space, arachnoid, subarachnoid, pia mater, brain
284
T/F Extent of external lesion is not reliable indicator of deeper lesions.
T
285
T/F Lethal lesion(s) of skull/brain may be small or absent.
T
286
What fracture? Secondary to contact with large flat object. Fracture begins along inner table.
Linear
287
What fracture? Fx associated with scalp laceration.
Compound
288
What fracture? Fx involving multiple bones
Complex
289
What fracture? Secondary to contact with small objects. (e.g. bullet, hammer)
Depressed
290
What fracture? Located distant from point of injury.
Contrecoup
291
What kind of hemorrhage? Between skull and dura, arterial bleeding
Epidural
292
What kind of hemorrhage? below dura with venous bleeding
Subdural
293
T/F SDH is more common in people with brain atrophy
T
294
Fracture contusion/laceration
at site of fracture and tend to be severe
295
Coup contusion
caused by bending/rebound of skull at site of injury
296
Contrecoup contusion
located distant, usually opposite from point of impact --> impact vs. impulsive loading
297
_____ contusions are most common on orbito-frontal surfaces and temporal poles.
Contrecoup
298
Elevated glutamate, activation of ATP Na/K pump, elevated intracellular Ca, and elevated lactic acid are signs of ____
severe concussion
299
Black Brain
Classical “Black Brain” of abused infant representing total brain necrosis secondary to shock a/o severe concussion.
300
GCS <= 8 is severe/moderate/minor
severe
301
Seizure
transient dysfunction of all/part of brain due to excessive discharge of a group of neurons causing sudden and transient symptoms of a motor, sensory, autonomic, or psychic nature
302
A seizure with an immediate precipitant such as fever, acute head trauma or CNS infection.
provoked seizure
303
A seizure without an immediate precipitant.
Unprovoked seizure
304
Recurrent unprovoked seizures.
Epilepsy
305
Motor seizure propagating along primary motor cortex
Jacksonian march
306
Drug for epilepsy that inhibits neurotransmission via GABA-A receptors.
Phenobarbitol
307
Which seizure? subtle, staring spells, no shaking/falling, no strange vocalizations
absence general
308
Which seizure? quick jerks, symmetrical, short
myoclonic general
309
Which seizure? grand mal
tonic-clonic general
310
Which seizure? quick body stiffening, fall
tonic general
311
Which seizure? bilateral rhythmic jerking
clonic general
312
Which seizure? loss of tone, slumping
atonic general
313
Seizures that "Start deep down in the center of the brain and spread quickly to both sides" are ___ seizures
generalized
314
T/F Focal seizures can occure with or without impairment of awareness
T
315
Seizures that start in a spot of the brain and may or may not spread are ____ seizures
focal
316
Which seizure? clonic shaking of contralateral limbs
motor strip focal
317
Which seizure? complex, bilateral hypermotor activity
anterior to motor strip near midline focal
318
Which seizure? arrest of activity, hypomotor
fronto-polar focal
319
Which seizure? aura, arrest of activity, unresponsiveness, motor automatisms
temporal lobe focal
320
Which seizure? sensory signs based on propagation to other lobes
parietal focal
321
Which seizure? visual signs
occipital lobe focal
322
3 mechanisms of reduced inhibition in epileptic brain
1. gaba receptor change, 2. loss of interneurons, 3. change of interneuron activity
323
3 mechanisms of excitation in epileptic brain
1. mossy fiber sprouting, 2. changes in EAA receptors, 3. presynaptic changes
324
general processes occurring in the brain before a patient develops spontaneous seizures after an insult is called ______
epileptogenesis
325
Paroxysmal depolarization shift
cellular correlate of focal interictal epileptiform spike/sharp wave --> prolonged Ca depolarization leading to sodium-mediated action potentials --> prominent after hyperpolarization due to opening of ca dependent k channels
326
T/F seizures involve loss of inhibitory control and runaway excitation (e.g. paired pulxse facilitation)
T
327
Sustained repetitive firing
mechanism of seizure generation similar to spikes in PDS but without Ca inward current--> voltage gated Na channels maintain threshold for spike generation
328
Mutations of what system might lead to absence epilepsy/generalized epilepsy
t-type calcium channel --> alterations in oscilllatory circuitry including changes in interaction between GABAb receptors, calcium channels, k channles in thalamus --> abnormal thalamocortical volleys between cortical layer 5 neurons and intralaminar nucleus of thalamus
329
Burst firing
hyperpolarization --> activation of TCa channel --> voltage dependent Na channel activation --> burst firing
330
GABA is excitatory/inhibitory during development
excitatory --> NKCC1 maintains high Cl in cell --> GABA activation leads to flow of Cl out of cell and depolarization
331
NMDA receptor in development
more readily expressed than AMPA --> GABA excitation more readily removes Mg block in NMDA receptors --> hyperexcitable state
332
Are GABA agnonists like benzodiazepines less useful during development?
No --> already in state of transition from excitatory GABA to inhibitory GABA so there is some benefit
333
_____ synchronized synaptic development across brain regions
giant depolarizing potentials
334
MOA: Na channel blockers
block voltage dependent Na channels @ high firing frequency --> inhibit sustained repetitive firing, indicated in focal epilepsy, oxcarbazepine, lamotrigine, phenytoin,
335
MOA: GABA agonists
increase inhibitory transmission --> prolong GABA mediated Cl channel opening (barbituates), increase frequency of GABA mediated Cl channel opening (benzodiazepines)
336
MOA: Ca channel blockers
blocks or modulates t-type calcium channels --> main effect on thalamic neurons --> prevents abnormal thalmo-cortical interaction --> absence seizures (valproic acid and ethosuximide)
337
MOA: EAA transmitter antagonists
multiple mechanisms to restore excitation/inhibition balance by reducing excitation --> 1. antagonize glutamate at AMPA/kainaite receptors (topiramate), 2. block voltage dependent t channels and Na (zonisamide), modulate NMDA receptor via strychnine-insensitive glycine receptor (felbamate)
338
MOA: Synaptic mechanisms
GABA reuptake inhibitors (vigabatrine, tiagabine), increase GABA (pregabalin), vesicle binding (Levetiracetam)
339
Ketogenic diet
high fat/low carb/low protein diet --> increase GABA production, ketones directly anti-epileptic
340
T/F B6 is a cofactor for gABA production and may support seizure therapy
T
341
Infections that trigger MS
EBV, HHV6, chlamydia, mycoplasma
342
T/F MS most often affects women
T
343
Which gene has the strongest association with MS?
HLA DRB1501 (MHC II)
344
Risk for MS among identical twins
30%
345
Risk for MS in fraternal twins
4%
346
Risk for MS among first degree relatives
4%
347
What symptom? painful inflammation of optic nerve
optic neuritis
348
What symptom? flexion of neck causing parasthesia
Lhermitte's
349
What symptom? symptoms exacerbated by overheating
uhthoff's
350
4 clinical patterns of MS
relapsing-remitting, secondary progressive, primary progressive, progressive relapsing
351
T/F MS respects vascular territories
F
352
Gadoliniumenhancing lesions suggest:
acute inflammation in MS
353
white matter lesions in MS suggest:
demyelination
354
black holes in MS suggest:
axonal loss, gliosis
355
Dawson's fingers
characteristic periventricular ovoid FLAIR hyperintense MSlesions
356
oligoclonal bands
if not present in serum, indicative of igg production in cns
357
Acute treatment of MS
corticosteroids, treat underlying infection
358
Disease modifying treatment of MS
inteferon 1a/b, natalizumab, etc.
359
The ____ is the master biological clock.
suprachiasmatic nucleus
360
Circadian clocks are based on _____ feedback loops
negative
361
Which two systems coordinate sleep temporally?
circadian system and homeostatic need for sleep
362
The circadian rhythm drives wakefulness/sleep
wakefulness
363
T/F Sleep drive is an oscillator.
F -->Sleep drive is a homeostatic system—not an oscillator—and as such it builds up and dissipates relative to the quantity and quality of sleep we obtain. It therefore promotes sleep to varying degrees. If sleep is not adequately satisfied physiologically, the homeostatic drive for sleep can build to a point at which the circadian system cannot maintain wakefulness. At this point, microsleeps and sleep attacks can occur when what people are trying to stay awake and engage in motivated behavior.
364
melanopsin cells—in our retinal ganglion cell layers transmit information about the environmental timing of Earth's light via the _____ tract to the hypothalamic suprachiasmatic nucleus (SCN).
retinohypothalamic
365
T/F Night shift work is better than longer shifts.
F --> night shifts not only build up sleep pressure but also force you to sleep in the wrong cycle which leaves you more exhausted because you can't sleep as fully.
366
Stages of sleep
waking --> sleepy, alpha activity --> stage 1 non-REM, theta --> stage 2, non-REM, sleep signals, delta wave --> stage 3/4 SWS, delta waves --> REM
367
During what stage of sleep do we give up thermoregulation?
REM
368
Declarative memory consolidation requires what kind of sleep?
non-REM
369
Emotional and procedural memory consolidation requires what kind of sleep?
REM
370
Cholinergic input from the ______ and the _____ nuclei project through the thalamus and facilitate thalamocortical transmission of arousal signals.
laterordorsal tegmental and pedunculopontine nuclei
371
Sleep switch
This internal biological clock originates in the suprachiasmatic nucleus (SCN), projects through the dorsomedial hypothalamus (DMH) sending inhibitory signals to the GABA(γ-aminobutyric acid)ergic (grey) ventrolateral preoptic nucleus of the hypothalamus (VLPO)
372
During the early hours of dark periods the pineal gland (Pin) releases melatonin (red), which has______ effects on the SCN and DMH of the melatonergic system.
inhibitory
373
With age we have more/less SWS
less
374
wake state instability
Once the homeostatic drive for sleep is elevated beyond levels typical of a normal waking day (16-18 hours) in a healthy adult, wakefulness can become unstable, as the sleep system turns on in the presence of waking drive, resulting in “lapses,” which refer to sudden unexpected delays in the brain’s responses.
375
The sleep drive accumulator is thought to be in the ____
basal forebrain
376
Narcolepsy tetrad
hypersomnolence, cataplexy, hypnogogic/hypnopompic hallucinations, sleep paralysis (and impaired sleep quality)
377
Cataplexy
sudden loss of muscle tone/partial loss common --> seconds to minutes, spared consciousness, triggered by emotion
378
Neurons secreting ______, produced in the ______, project widely to areas of brain involved in sleep-awake control; this substance is diminished or absent in narcolepsy with cataplexy.
hypocretin/orexin in the posterolateral hypothalamus
379
Flipflop switch model
awake/sleep is a balance between LC/TMN/Raphe nuclei/VLPO/eVLPO --> orexin supports wakefulness and is inhibited by VLPO
380
Treatment for hypersomnolence
stimulants, modafinil, armodafinil, naps
381
Treatment for cataplexy
tricyclic antidepressants, SSRI, gamma hydroxybutyrate (Xyrem)
382
An undesirable behavioral,motor, or sensory phenomenon which occurs intermittently during sleep.
parasomnia
383
T/F Parasomnias can emerge from rem/non-rem sleep.
T
384
Disorders of arousal begin in non-REM/REM sleep.
non-REM
385
T/F arousal disorders tend to have positive family history.
T
386
Tx for arousal disorders
reassurance, secure environment, warning devices, benzodiazepines, avoiding stressors
387
T/F sleepwalking is less likely when sleep deprived.
T
388
Dissociated state characterized by violent dream-enacting behavior, increased tonic/phasic EMG in REM, absence of epileptiform activity is ______
REM sleep behavior disorder
389
Normally, REM sleep-generating neurons in the _____ actively inhibit spinal interneurons in descending tracts.
pons
390
T/F RBD is a neurodegenerative condition
T
391
T/F RBD is most common in older men.
T
392
T/F RBD is not associated with PD, Lewy Body, or multi-system atrophy.
F
393
Tx of RBD
clonazepam, melatonin, secure environment
394
REM sleep behavior disorder typically presents in patients 10-20 years after diagnosis of ____
PD
395
_____: an awake sensory phenomenon with a volitional motor response.
Restless legs
396
____: an involuntary sleep-related motor phenomenon.
Periodic leg movements
397
RLS URGE criteria
urge to move legs with dyesthesias, onset with rest or inactivity, partial or total relief with movement (Getting up), symptoms worse in evening or night
398
Secondary RLS may be related to 3 conditions
iron deficiency anemia, pregnancy, chronic renal failure
399
Link between iron and RLS
low iron --> impaired central dopaminergic supra-spinal inhibition
400
RLS/PLM affects sensory afferents.
RLS
401
RLS/PLM affects motor efferents
PLM
402
Tx of RLS
dopamine agonists, opiates, gabapentin, iron, benzodiazepines
