Chapter 28-The CNS Flashcards
(558 cards)
1
Q
What vulnerability do neurons in the brain regions show and what is meany by it
A
Selective vulnerability, as some parts of the brain are more susceptible to different agents than others due to different NT used, locations, etc
2
Q
What is the state of cell division in mature neurons
A
Incapable
3
Q
What is the classical sign of an acute neuronal injury and when are the seen
A
Aka red nucleus, seen 12 to 24 hours after hypoxia/ischemic event
4
Q
What event is characterized by shrinkage of cell body, pyknosis of nuclear strength, dissapreance of nucleoli, loss of Nissl substance, and intense eosinophilia
A
Acute neuronal injury
5
Q
Which event is characterized by red nucleus
A
Acute neuronal injury
6
Q
What condition is characterized by reactive gliosis
A
Subacute or chronic neuronal injury/degeneration
7
Q
What is axonal reaction and where is it commonly seen
A
Change in the cell body during regeneration of the axon, most commonly seen in the anterior horn
8
Q
What are neuronal inclusions
A
Manifests with aging and are intracytoplasmic accumulation of complex lipids, proteins, and carbs
9
Q
When are Cowdry bodies seen
A
Intranuclear inclusions seen in herpetic infection as a result of viral infection
10
Q
When are Nehru bodies seen
A
Cytoplasmic inclusions seen during rabies infection
11
Q
When are neurofibrillary tangle seen
A
Alzheimer’s
12
Q
When are Lewi bodies seen
A
Parkinson’s
13
Q
When is abnormal vacuolization of the perikaryon and neuronal cell process in the neurophil seen
A
CJD
14
Q
What is the most important histopathological indicator of CNS injury
A
Gliosis
15
Q
What is gliosis characterized by
A
Hyperplasia and hypertrophy of astrocytes
16
Q
What protein is characteristic of astrocytes
A
Glial fibrillary acidic protein (GFAP), an intermediate filament
17
Q
What is the function of astrocytes
A
- Metabolic buffers and detoxifier of the brain
- Barrier function on control flow of macromolecules between the blood, CSF and brain
18
Q
What is the morphological feature of gliosis
A
Astrocyte’s nucleus become enlarged, vesicular, and prominent nucleoli
19
Q
What astrocyte is characterized by changes to grey matter cell with a large nucleus, pale staining central chromatin, intranuclear glycogen droplet, and a prominent nuclear membrane and nuceolus
A
Alzheimer’s type 2 astrocyte
20
Q
Which conditions cause Alzheimer type 2 astrocyte changes
A
- Long standing hyperammonemia in chronic liver disease
- Wilsons disease
- Hereditary disorders in the urea cycle
21
Q
What proteins are contained in the Rosenthal fibers
A
Heat shock protein alphabeta-crystallin
Heat shock protein hsp27
Ubiquitin
22
Q
Rosenthal fibers are indicative of what
A
Pilocytic astrocytoma
23
Q
Where are Rosenthal fibers usually found
A
Regions of long standing gliosis
24
Q
Alexanders disease is associated with mutations in which gene
A
Encoding GFAP
25
IN Alexander’s disease, where are Rostenthal fibers found
Periventricular, verivascular, and subpial locations
26
Corpora amylacea are commonly found in which condition
Aka polyglucosan bodies found in Alexanders disease
27
Lafora bodies are commonly found with which location
Myoclinic epilepsy
28
What is the response of microglia to injury
- Proliferation
- elongated nuclei (rod cells)
- forming aggregates around foci of necrosis (microglial nodules)
- congregating around cell bodies of dying neurons (neuronophagia)
29
How many neurons do oligodendrocytes usually myelinate
Multiple neurons as opposed to the 1 to1 of Schwann cells
30
What is a feature of acquired demyelination game disorders and leukodystrophies
Injury to oligodendrocytes
31
What is harbored in oligodendrocytes in progressive multifocal leukoencephalopathy
Viral inclusions
32
What is found in multiple system atrophy (MSA)
Glial cytoplasmic inclusions (aka oligodendrocytes with alpha-synuclein)
33
What is found in oligodendrocytes in multiple system atrophy (MSA)
Alpha-synuclein
34
Damage to ependymal cells result in what
Ependymal granulations, which are proliferation of sub ependymal astrocytes
35
What infectious agents in particular causes extensive ependymal injury
CMV
36
What is vasogenic edema
Increase in ECF by blood brain barrier disruption and increased Vascular permeability. This results in fluid going from intravasular compartment to intercellular spaces
37
What is cytotoxic edema
Increased in ECF secondary to neuronal injury, resulting in the prevention of maintaining normal membrane gradients
38
What is the physical result of edema
Gyro are flattened, sucking are narrowed and ventricular cavities are compressed
39
What is hydrocephalus
Accumulation of CSF in the ventricular system
40
What is the most common cause of hydrocephalus
Impaired flow and resorption of CSF
41
What is noncommunicating hydrocephalus
aka obstructive hydrocephalus, and the ventricular system does not communicative with the subarachnoid space
42
What usually causes a noncommunicating hydrocephalus
Blockage of the third ventricule due to a mass
43
What is hydrocephalus ex vacuo
Enlarging of the ventricular space due to loss of the brain parenchyma
44
What occurs during a subfalcine/cingulate herniation
Unilateral or asymmetrical expansion of the cerebral hemisphere where the circular gyrus herniated under the falx
45
What structures can become compressed during a subfalcine/cinguate herniation
Anterior cerebral artery and its branches
46
What occurs during a transtentorial herniation
Medial aspect of the temporal lobe is compressed against tentorium
47
Which structures are affected during transtentorial herniation
- Third cranial nerve (pupil dilation and loss of EOM on side of lesions)
- posterior cerebral artery and ischemia to primary visual cortex
- Kernohan notch
- Duret hemorrhage’s
48
What is kernohan notch
Contralateral cerebral puduncle is compressed, resulting in ipsilateral hemiparesis
49
What are duret hemorrhages
lesions in the pons and midbrain. In linear or flame shape due to tearing of veins and arteries supplying the upper brainstem
50
What accounts for the most CNS malformations and what is the most common structure involved
Neural tube defects, with most involving the spinal cord
51
What is spinal dysraphism
Aka spina bifida, which is disorganized segments of spinal cord. Associated with overlying meningeal out pouching
52
What is a myelomeningocele
Extension of the CNS tissue through a defect in the vertebral column
53
Where do most myelomenigoceles occur
Lumbosacral regions
54
What is an encephalocele
Brain tissue extending through a defect in the cranium (commonly the posterior fossa)
55
What is the rate of recurrent neural tube defects in subsequent pregnancies
4-5%
56
When does folate supplementation need to occur to be affective
First 28 days
57
What is an anencephaly
Malformation in the anterior end of the neural tube with the absence of brain and calvarium
58
During anencephaly, what is area cerebrovascusa
Disrupted forebrain development, resulting in disorganized brain tissue with mixed ependymal, choroid plexus, and meningothelial cells
59
What is the path of migration for those cells that are to become excitatory neurons
Radial migration
60
What is the migration pattern for those neurons that are to become inhibitory neurons
Tangential
61
Fo radial migration, which protein is secreted
Aka for excitatory neurons, reelin is secreted to migrating neuroblast
62
What is Lissencephaly
Reduction in the number of gyri
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What is the most extreme case of lissencephaly
Agyria or complete lack of gyri
64
Which type of lissencephaly is associated with smooth surface
Type 1
65
Type 1 lissencephaly is associated with which mutation
Disruptions in signaling for migration and cytoskeleton motor proteins that drive migration
66
Which type of lissencephaly is associated with rough or cobblestones
Type 2
67
Type 2 lissencephaly is associated with what mutations
Genetic abnormalities that disrupt the stop signal for migration
68
What is polymicrogyria
Small unusually numerous irregular formed cerebral convolutions
69
What are neuronal heterotopias assoacited with
Epilepsy
70
What are periventricular heterotopias commonly caused by
- Mutations in coding for filamin A. (Acting binding protein in assembly of meshwork)
- Doublecortin (DCX) microtuble associated protein
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Filamin A gene is located in what location and what is the result in each gender
On X chromosome
- Male-lethal
- Female-periventrular heterotopia
72
Where is the gene for DoubleCortin protein (DCX) located
X chromosome
73
What is the result of a mutation in DCX gene in each gender
Male-lissencephaly
| Female- subcortical band heterotpias
74
What is holoprosencephaly
Incomplete separation of the cerebral hemisphere across the midline
75
What are common malformation seen as part of a holopresencephaly
- cyclopia
| - arrhinencephaly (absence of olfactory cranial nerves)
76
What is holoprosencephaly associated with
Trisomy 13
| Mutations in sonic hedgehog
77
What is the radiological finding in agenesis of corpus callosum
“Bat wings” as a result of misshapen lateral ventricle
| -bundles of anteropoteriorly oriented white matter
78
What are the characteristics of Arnold-Chiari type 2 malformation
- Small posterior fossa
- misshapen midline cerebellum with downward vermi through foramen magnum
- variable, but hydrocephalus and lumbar myelomeningocele
- Caudal displacement of medulla, tectum, aqueductal stenosis
79
What are the characteristics of Chiari type 1 malformation
Less severe than type 2
| -Low lying cerebellar tonsils extend down into the vertebral canal
80
What are the characteristics of a Dandy Walker malformation
- Enlarged posterior fossa
- Cerebellar vermis is absent or barely present
- Large midline cyst as a expanded roofless fourth ventricle
81
What is commonly found in assoacition with Dandy-walker malformation
Dysplasia of the brain
82
What is Joubert syndrome
Hypoplasia of the cerebellar vermis with elongation of the superior cerebellar peduncles
- altered shape of brain stem
- molar tooth sign
83
What is the radiological sign seen in Joubert syndrome
“Molar tooth sign”
84
What is the common cause of Joubert syndrome
Mutations in genes coding primary (non-motile) cilium
85
What is hydromylia
Expansion of ependymal lined central canal of cord
86
What is a syringomyelia aka syrinx
Fluid filled cleft like cavity in the inner portion of the spinal cord
87
What is a syringobulbia
Fluid filled cleft like cavity extending into the brainstem
88
Syringomyelia are associated with which conditions
- Chiari malformations
- intraspinal tumors
- traumatic injury
89
What are the clinical presentations of syrinx
Isolated loss of pain, temperature and in the upper extremities due to involvement of the anterior commisure
90
What is cerebral palsy
Nonprogressibe neurological motor deficit with ataxia, spasticity, paresis as a result of injury during the prenatal and perinatal period
91
What condition is characterized by ataxia, spasticity, paresis
Cerebral palsy
92
Which population is at a higher risk for intraparenchymal hemorrhage
Premature infants
93
Where are parenchyma hemmorages commonly occurring
In the terminal matrix near the junction between developing thalamus and caudate nucleus
94
Which population is at a higher risk for periventricular leukomalcias
Aka supratentorial periventricular white mater
Premature infants
95
How to periventricular leukomalacias present
Chalky yellow plaques in regions of white matter necrosis and calcification
96
What is multicystic encephalopathy
White and grey matter involvement in ischemic damage resulting in cystic lesions throughout the hemisphere
97
During perinatal ischemic lesions of the cerebral cortex, where is most of the damage seen
Depths of the sulci, resulting in thinned out gliosis gyri
98
What is ulegyria
Thinned out and gliotic gyri as a result of ischemic lesions
99
What is status marmoratus
the marble like appearance of the deep nuclei as a result of an ischemic event in the sulci of the cerebral cortex
100
What is the order of events in an ischemic event of the cerebral cortex
- Ulegyria (thinned out sulci)
| - Status marmoratus (marbled like appearance)
101
What are commonly seen symptoms following damage the cerebral cortex
Movement disorders (choreoarthetsis) due to damage to putamen, caudate, and thalamus
102
What is a displaced skull fracture
Fracture of the bone is displaced into the cavity greater than the thickness of the bone
103
What is a diastic fracture
Fractures that cross suture lines
104
Which portion of the brain is most susceptible to concussion and physical injury
Crests of the gyri
105
What is a coup brain injury
The brain injury is on the same side as the impact
106
What is a counter coup brain injury
Injury is on the opposite side of the impact
107
What is the common injury if the head was immobile at the time of the impact
Coup
108
How long does the morphological signs of brain trauma take to appear
24 hours
109
What are plaque Jaune and what do the signify
They are depressed, retracted, yellowish brown patches at the crest of the gyri, commonly at the countercoup sites of injury.
110
What is diffuse axonal injury characterized by
Widespread, often asymmetrical axonal swelling within hours
111
What is the stain of choice for diffuse axonal injury
Immunoperoxidase stains for amyloid precursor protein and alpha-synuclein
112
Why are older patients more prone to subdural hematomas following injury
Brain atrophy with age causes bridging veins to stretch and easy torn
113
What occurs in the first week of acute subdura hematomas
Lysis of the close
114
What occurs during the second week of acute subdural hematomas
Growth of fibroblasts from the Dural surface into the hematoma
115
What occurs during 1-3 months following acute subdural hematoma
Early development of the hyalinized connective tissue
116
What are the morphological signs seen in an acute subdural hematoma
Freshly clotted blood along the brain surface without the extension into the sulci
117
What portion of the brain are subdural hematomas commonly seen
Lateral cerebral hemispheres, bilateral in 10% of pts
118
What is the cause of post traumatic hydrocephalus
Obstruction of CSF absorption from hemorrhage into the subarachnoid space
119
What is the cause of chronic traumatic encephalopathy
Aka CTE or Demetria pugilistica
From repeated trauma and blows to the head
120
What do brains in patients with CTE look like
Atropine, enlarged ventricles, accumulation of tau proteins, involving the frontal and temporal lobe
121
How does cerebral vascular disease rank on leading causes of death
Third
122
What are the two forms seen in cerebrovascular disease
- Hemorrhage (rupture of blood vessel in CNS)
| - hypoxia, ischemia, and infarction (impaired blood flow to CNS)
123
What is released and the process of neuronal cell death
Excitatory amino acids (Glut), leading to NMDA receptors and the influx of calcium
124
What is the penumbra
At risk area that is the transition area from the necrotic tissue to normal brain tissue
125
When does global cerebral ischemia occur
Generalized reduction in cerebral perfusion (cardiac shock/arrest, severe hypotension
126
What are the most sensitive cells in the CNS
Neurons
127
What are the most sensitive neurons in the brain
- Pyramidal cell layer in the hippocampus (CA1 aka Sommer sector)
- Cerebellar purkinje cells
- pyramidal cells in cerebral cortex
128
What is the Sommer sector
The hypoxic sensitive pyramidal neurons in the hippocampus
129
What are watershed infarcts
Areas most distant to arterial blood supply, usually between two sources of arterial blood
130
Where in the cerebral hemisphere is most sensitive to arterial blood disruptions
Between anterior and middle cerebral artery
131
When are border zone infants usually seen
Following Hypotensive episodes
132
What is the common exact location of watershed infarcts seen
Sickle shaped band of necrosis over the cerebral convexity just lateral to the interhemispheric fissure
133
What are the early changes (12-24 hours)seen in brain ischemia
- microvasculization
- eosinophilia of neuronal cytoplasm
- nuclear pyknosis and karyorrhexis
134
What are the subacute changes seen in ischemic events of the brain
24 hour to 2 weeks
- tissue necrosis
- influx of macrophages
- vascular proliferation
- reactive gliosis
135
What is pseudolaminar necrosis
Neuronal loss and gliosis of the cerebral neocortex is uneven, where there is preservation of some layers, yet destruction of others
136
When does a focal cerebral inshemic event occur
Reduction of blood flow to a localized area of the brain due to arterial occlusion or hypoperfusion
137
What is the most common emboli leading to focal cerebral ischemia
Cardiac mural thrombi > atheromatous plaques in carotid
138
What are the predisposing conditions for an embolism
- MI
- Valvular disease
- Arterial fibrillation
139
Which artery territory is most at risk for an embolism
Middle cerebral artery (off of internal artery)
140
What are thrombolism occlusion most commonly associated with
-Athersclerosis, hypertension, diabetes, and plaque ruptures
141
What are the most commonly locations for a thrombolism
Carotid bifurcation, origin of MCA, basilar artery
142
What are the common causes of infectious vasculitis that leads to thrombi
- TB
- syphilis
- immunosuppression
- opportunistic infections
143
What is the correlation between polyarteritis nodosa and infarcts of the brain
A noninfectious Vasculitis causing an infarct
144
How do secondary hemmorages of the brain occur and there are their characteristics
- Occurs due to ishechmia-reperfusion injury due to collateral flow or fragmentation of intravascular occlusive material
- Results in petechial hemorrhage
145
In nonhemorrhagic infarcts, what is the extent of appearance changes in the first 6 hours
No changes
146
What is the extent of appearance changes in nonhemorrhagic infarcts at time of 48 hours
looks pale, soft, swollen, and corticomedulary Junction becomes indistinct
147
Following an nonhemorrhagic infarct, what is the microscopic appearance after 12 hours
Ischemic neuronal changes with both cytotoxic and vasogenic edema
148
Following an nonhemorrhagic infarct, what is the microscopic appearance after 48 hours
Neutrophilic emigration increases, then falls off
| -monocyte derived cells become the dominate cell type until week 3
149
Following an nonhemorrhagic infarct, what is the microscopic appearance of reactive astrocytes
Can be seen 1 week following the infarct
150
Which conditions increases the risk for hemorrhagic infarcts
Carcinoma
Localized infections
Anything leading to hypercoagability
151
What is a main cause of lacunar infarcts
Hypertension
152
What are the characteristics of a lacunar infarct
Cave like infarct less that 15 mm wide
| -Usually the deep vessels of the brain
153
What is the location of lacunar infarcts from most common to lesser
```
1-Lenticular nucleus
2-thalamus
3-internal capsule
4-deep white matter
5-caudate nucleus
6-pons
```
154
What is etat crible
Widening of the perivascular space without tissue infarction
155
What condition causes slit hemorrhages
Hypertension
156
What are the characteristics of slit hemorrhages
Small hemorrhages surrounded by focal tissue destruction and pigment laden macros
157
What is a acute hypertensive encephalopathy
Malignant hypertension causes cerebral dysfunction, which causes headaches, confusion, vomiting, and convulsions
158
What is binswanger disease
Brain injury due to lack of blood flow that is preferentially the subcortical white matter with myelin and axon loss
159
Which population is at the highest risk for intraparenchymal hemorrhages
Middle to late adult life, peaking at 60 years old
160
What are the 2 main causes of ganglionic and lobar hemorrhages
Hypertension
| Cerebral amyloid hemorrhages
161
What is the main risk factors assoacited with deep brain parenchyma hemorrhages
Hypertension
162
Which deep structure hemorrhages are commonly damaged as a result of hypertension
Deep white/grey matter
Brainstem
Cerebellum
163
What are Charcot Bouchard microaneurysms and where are they commonly occurring
Hypertension caused minute aneurysms, commonly seen in the basal ganglia
164
What is the most common location of a hypertensive intraparenchymal hemorrhage
Putamen (50 to 60% of cases)
165
Which condition is most commonly associated with lobar hemorrhages
Cerebral amyloid angiopathy (CAA)
166
The presence of which allele increases the risk of bleeding due to CAA
Epsilon 2 or 4
167
CAA is usually restricted to which vessels
Leptomeningeal and cerebral cortical arterioles and capillaries
168
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is associated with mutations in which gene
Notch3
169
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a disease of dysfunction in which structures
Vascular smooth muscle
170
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) results in which events
Repeat strokes
171
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) will result in which finding in the arteries of the CNS
Concentric thickening of media and adventitia, loss of smooth muscle cells, basophilic, PAS positive deposits
172
What is the most common cause of clinically significant subarachnoid hemorrhage
Rupture of a saccular “berry” aneurism in a cerebral artery
173
What is the most common intracranial aneurysm
Saccular, aka Berry’s
174
Where are most saccular aneurysms located
About 90% in the anterior portion of circulation
175
When is a rupture of an aneurysm most likely to occur
Acute increases in intracranial pressure, especially in the 5th decade of life
176
What is the most common type of clinically significant vascular malformation
Arteriovenous malformations (high pulsating blood flow)
177
What is fox-alajouanine malformation
Venous angiomatous of the spinal cord, most commonly in the lumbosacral region. It is associated with ischemic injury to spinal cord and progressive neuro symptoms
178
Which population is more likely to develop a vascular malformation
Males are twice as likely
179
What is the most common site for arterialvenous malformations in the brain
Middle cerebral artery, in particular their posterior branches
180
What is the most common cause of bacterial meningitis in neonates
Strep B
| E. Coli
181
What is the most common cause of meningitis in older individuals
- Step pneumonia
| - listeria
182
What is the most common cause of meningitis in adults
Neisseria meningitidis
183
What are the symptoms of meningitis
- irritations and neuro impairment
- headache
- photophobia
- stiff neck
184
What is the typical spinal tap result from someone with bacterial meningitis
Increased protein concentration
| Decreased glucose concentration
185
What is the Waterhouse Friderichsen syndrome
Meningitis associated septicemia with hemorrhagic infarction of the adrenal gland
186
Where is the purulent exudate commonly found in meningitis caused by H. Influenza
Basal
187
Where is the purulent exudate commonly found in meningitis caused by pneumococcal bacteria
Cerebral convexities
188
What is the condition of chronic adhesive arachnoiditis
Pneumococcal meningitis infections lead to capsular polysaccharide production resulting in a gelatinous exudate that promotes fibrosis
189
What are the CSF finding in aseptic meningitis
- lymphocytic pleocytosis (increased amount)
- Moderate protein elevation
- Normal glucose
190
When can an asymptomatic like meningitis arise without there actually being an infection of any kind
Rupture of a epidermis cyst into the subarachnoid space or introduction of a chemical irritant. There will still be neutrophils in the CSF, along with normal glucose and slightly elevated protein levels
191
What is a brain abscess
Necrosis of brain tissue along with inflammation, commonly due to a bacterial infection
192
What are predisposing conditions for a brain abcess
Acute bacterial endocarditis
Congenital heart defects with right to left shunting
Loss of pulmonary filtration of organisms
Chronic pulmonary sepsis (example: bronchiectasis)
Systemic infection (usually due to immunosuppression)
193
What is the CSF concentration in patients with a brain abscess
High white count
Increased protein concentration
Normal glucose levels
194
What are the most common causes of brain abscess
Staphy and streptococci
195
What leads to a subdural empyema
Infections of the skull bones or air sinuses that spread to the subdural space
196
What is the process of complications following a subdural empyema
Produces a mass effect or thrombophlebitis of the bridging veins that cross the subdural space, resulting in venous occlusion and infarction
197
What is the CSF concentration of subdural empyema
Similar to brain abcess with:
- High white count
- Normal glucose
- Elevated protein
198
What are extramural abscesses associated with
Osteomyelitis, usually arising from an sinisitis or surgical procedure
199
What are the clinical presentations of a patient with TB meningitis
Headache, malaise, mental confusion, vomiting
200
What is the CSF profile of TB
Pleocytosis of monocytes, sometimes neutrophils are included
Elevated protein
Reduced or normal glucose
201
What is the most serious complication associated with chronic TB meningitis
- Arachnoid fibrosis producing hydrocephalus
- obliterating endarteritis resulting in arterial occlusion
- infarction of brain
202
What is the most common pattern of TB involvement in the brain
Meningoencephalitis
203
What are the contaminates seen in the arachnoid space during TB meningitis
-gelatinous or fibrinous exudate involving the base of the brain
204
What are the clinical presentations of Neurosyphilis
- Menigovascular syphilis
- paretic neurosyphilis
- tabes dorsalis (loss of coordinated movement)
205
What is meningovascular neurosyphilis
Chronic meningitis involving the base of the brain, and sometimes obliterating endarteritis with perivascular inflammation
206
What is paretic neurosyphilis
Invasion of the brain resulting in damage to the frontal lobe with loss of neurons, proliferation of microglia, gliosis, and iron deposits
207
What is tabes dorsalis
Loss of sensory axons in the dorsal roots, resulting in ataxia, loss of pain, joint damage, “lightning pains”, and loss of deep tendon reflexes
208
What are the general symptoms seen in patients with Arbor virus encephalopathy
Seizures, confusion, delirium, stupor, coma, reflex asymmetries and ocular palsies
209
What are the characteristics of the brain changes seen in Arboviruses
Perivascular accumulation of lymphocytes, neuronophagia (engulfing of necrotic neural debris, and microglial nodules
210
HSV 1 encephalitis occurs in which age group
Children and young adults
211
HSV 1 encephalitis will present with which symptoms
-alterations in mood, memory and behavior
212
Which mutation population are at a higher risk for HSV1 encephalitis
TLR3 signaling mutations
213
Where does meningitis caused by HSV 1 begin
Inferior and medial regions of Temporal lobe, and the orbital gyri of frontal lobes
214
What is found in the neurons and glia during an HSV 1 encephalitis
-Cowdry type A inclusion bodies
215
Which population is commonly affected by CMV and what does it cause
Subacute encephalitis in immunocompromised individuals
216
Where does the CMV tend to accumulate and what is the result
Accumulates in the paraventricular subependymal regions of the brain, where it causes severe hemorrhaging and necrosis of the ventricles and choroid plexus
217
Where is the target location for polio virus
Anterior horns of the motor neuron
218
How does the CSF present with poliomyelitis
Same as aseptic meningitis
219
Which infection is characterized by the presence of Negri bodies
Rabies infection
220
What is the pattern of infection during a rabies infection
Ascending, starting with the peripheral nerves of the wound, and moves into the CNS (1 to 3 months)
221
What is the diagnostic clinical symptoms leading to rabies
-Local paresthesias around the wound, along with malaise, fever, headache
222
What are the clinical symptoms of a severe and late infection of rabies
CNS excitability with extreme movements and exaggeration of pain on even the slightest of touches
223
What is the only CNS cell type that contains both targets for HIV and what are they
Microglia contain both CCR5 and CXCR4
224
What is immune reconstitution inflammatory syndrome and what infection is it associated with
Patients with AIDS that have received treatment, deteriorate due exacerbation of symptoms from opportunistic infections
225
With HIV encephalitis, what are the histological findings
Widely distributed microglial nodules with multinucleated giant cells
226
What is progressive multifocal leukoencephalopahy (PML) caused by
JC virus
227
How does the JC virus cause PML
JC virus targets the oligodendrocytes, leading to demyelination
228
Which patient population is at risk for PML caused by JC virus
Immunosuppressed
229
What are the histological characteristics of Progressive Multifocal Leukoencephalopathy (PML)
Patches of irregular, ill defined white matter injury, usually demyelination in the subcortical area
230
What are the characteristics of the lesions in PML
Scattered laden macrophages with enlarged oligodendrocyte nuclei containing glassy amphophilic viral inclusions
231
What are the clinical signs of subacute sclerosing panencephalitis (SSPE)
Cognitive decline, spasticity of limb, and seizures
232
Subacute sclerosing panencephalitis is commonly seen months to years after which initial infection
Measles
233
How is SSLE characterized in the brain
Gliosis, degeneration of myelin, viral inclusions in the oligodendrocyte nuclei
234
What do the viral inclusions in SSLE contain
Nucleocapsids characteristic of measles, with the measles virus antigen being present
235
What are the three main forms of fungal infection in the CNS
- Chronic meningitis
- Vasculitis
- parenchymal invasion
236
Which structures are affected during cryptococcal meningitis
Basal leptomeninges, which can obstruct the foramine of Luschka and Magendie causing hydrocephalus
237
Which infection is characterized by “soap bubbles”
Cryptococcal infection
238
What are the clinical presentations of an infection with malaria
Reduction in cerebral blood flow, ataxia, seizures, coma, and long term cognitive deficits
239
What is the conformational change that is seen in prions that lead to pathogenesis
Change from the alpha helix isoform (PrPc) to beta sheet (PrPsc)
240
Mutations in which gene have shown in familiar forms of prion diseases
PRNP
241
Which codon number and amino acids influence the chances of obtaining a prion disease
Homozygous for either Met or Val at codon 129
242
Mutations in which gene are responsible for CJD
PRNP
243
What is a clinical symptom of CJD
Startle myoclonus (involuntary muscle jerking upon sudden stimulation)
244
What is the distinguishing feature of vCJD
No alteration in PNRP, only 129 codons affected, but has the precedence of cortical plaques surrounded by halo of spongiform change
245
What is fatal familial insomnia (FFI) caused by
Mutations in the PRNP gene leading to an asparagine to an aspartate change at residue 178 along with MET at 129
246
What disease is caused by a PRNP mutation to an aspartate at 178 along with a methionine are 129
FFI
247
What disease is caused by a PRNP mutation with an aspartate change at 178 with a valine at 129
CJD
248
What is the change in pathology that separates FFI from other prion diseases
Neuronal loss and reactive gliosis in the anterior ventral and dorsomedial thalami nuclei, along with the inferior olivary nuclei
249
What are leukodystrophies
Inherited disorders that affect synthesis or turnover of myelin components
250
What is the most common demyelination disorder
Multiple sclerosis
251
What is MS characterized by
Autoimmune demyelination due to white matter lesions
252
What is the rare of cases of MS between genders
Women are twice as likely to acquire it
253
What is the normal clinical cycle involved in MS
Relapsing and remitting episodes of impaired neurological function, followed by a time of partial recovery
254
How is MS correlated with genetics
Very with 15x more likely if a dizygotic twin with 150x more likely with monozygotic
255
Which genetic component is relegated with in increase in MS
DRB1*1501, with each acquired copy increasing the risk by 3x
256
What is the immune mechanism of MS
Initiated by TH1 and TH17, followed by the production of IFNgamma and subsequent inflammation, macrophage and lymphocyte recruitment follow
257
Where do the plaques in MS generally tend to accumulate
Adjacent to the lateral ventricles, optic nerve/chiasm, brain stem
258
During MS, what are the characteristics of an active plaque
Ongoing myelin breakdown associated with abundant macrophage containing PAS debris
259
During MS, what are the characteristics of an inactive plaque
Little to no myelin found, reduced number of oligodendrocytes, but an increased gliosis and astrocyte proliferation
260
What are shadow plaque indicative of
During MS, where there is partial and incomplete regeneration of myelin from the surviving oligodendrocytes
261
What is the common initial clinical manifestation of MS
Unilateral visual impairment due to involvement of the optic nerve
262
What is the make up of the CSF during MS
- Mild elevation of protein
| - IgG levels elevated
263
What are the clinical presentations of Neuromyelitis optica (NMO)
Synchronous bilateral optic neuritis and spinal cord demyelination
264
Which gender is more commonly affected by Neuromyelitis optica (NMO)
Females
265
What is the characterizing feature of Neuromyelitis optica
Antibodies against aquaporin 4
266
What is present in the CSF during NMO
White cells, including neutrophils
267
What are the clinical symptoms of acute disseminated encephalomyelitis
Monophasic demyelination disease characterized by rapid onset of headache, lethargy, and coma
268
What is the ultimate outcome of acute disseminated encephalomyelitis
Death in 20%, the rest recover completely
269
When does acute disseminated encephalomyelitis occur
Week or 2 after viral infection or viral immunization
270
What is are the characteristics of acute necrotizing hemorrhagic encephalomyelitis
CNS demyelination affecting young adults and children, resulting in death or severe deficits
271
When does acute necrotizing hemorrhagic encephalomyelitis occur
Following a recent upper respiratory infection
272
What are the characteristics of pathogenesis of Central Pontine Myelinolysis
Acute disorder with demyelination of Basis Portis and pontine integument
273
When does central pontine myelitis occur
2 to 6 days after rapid correction of hyponatremia, but possible with other electrolyte disturbances
274
What disease is osmotic demyelination disorder
Central pontine myelinolysis
275
What is the characteristics of damage to cells in central pontine myelinolysis
- Absence of inflammation, neurons and axons well preserved
| - All lesions are at the same stage of myelin loss and reaction
276
What are the clinical symptoms seen in central pontine myelinolysis
Rapidly evolving quadriplegia
| -“locked in syndrome”(fully conscious but unresponsive”)
277
What is the pathological process that is common across most of the neurodegenerative diseases
Accumulation of protein aggregates aka proteinopathy
278
What is the location that tau protein will accumulate
Produced intracellular lay and stay Extracellular
279
Where does the protein AB in Alzheimer disease (AD) accumulate
Neuropil
280
What is the critical initiation event for the development of Alzheimer disease
Accumulation of AB protein
281
Which genomic abnormality and condition is associated with AB protein and Alzheimer disease
APP, which is located on chromosome 21, so Down syndrome is commonly associated with AD
282
What is the result if the APP is cleaved at the alpha secretaries site
Soluble fragment is produced and non amyloidosis portion
283
What is the result when the APP in AD is cleaved at the beta secretary site
Generates the AB protein that forms the plaque
284
How do the different cleavage site for APP protein differ in size
AB 42 is the protein that starts the formation of plaques
285
In the cleavage of APP, what are the components of gamma secretary complex
- presenilin
- nicastrin
- Pen-2
- Aph-1
286
In AD, what is the location of PS1
Chromosome 14
287
In AD, what is the location of PS2
Chromosome 1
288
What is the process of tau becoming an inclusion
There is the development of tangles, which causes a shift to somatic-dendritic distribution, hyperphosphorylated and can no longer bind to microtubules
289
Which pathogenesis of AD correlates well with the degree of dementia
Number of neurofibrillary tangles
290
During the course of AD, where in the brain is the effect seen
Cortical atrophy and widening of the cerebral sulci in the frontal, temporal, and parietal lobes
291
What is hydrocephalus ex vacuo
The widening/enlargement of the ventricles as a result of brain atrophy
292
Where are plaques during AD normally seen
Hippocampus, amygdala, neocortex
293
What are diffuse plaques and where are they found
Deposition of AB plaques found in the basal ganglia and cerebral cortex that have the amyloid characteristics but lack the surrounding neurotic processes
294
What are the characteristics of the neurofibrillary tangles
Tau containing bundles that are in pyramidal neurons that have an elongated flame shape or rounded “globose” tangles
295
What is an almost invariable accompany of AD
Cerebral amyloid angiopathy, which are AB40 plaques
296
What is the common terminal event that will kill a patient with AD
Intercurrent disease, usually pneumonia
297
What are the FTLDs locations of damage
Aka frontotemporal lobar degenerations, so the frontal and temporal lobes
298
How are FTLDs distinguished from Alzheimer’s disease
Alterations in personality, behavior and language (aphasia) proceeds memory loss
299
Picks disease is classified under which neurodegenerative disease
FTLD-tau
300
What is the diagnostic feature for Pick disease and subsequent FTLD-tau
-Pick bodies, which are smooth contoured inclusions, along with severe atrophy of the frontotemporal lobes
301
IN FTLD, which layers are generally seen to have the most severe neuron loss
Outer three layers
302
What is the most common genetically caused FTLD-TDP
Expansion of hexanucleotide repeat in the 5’ UTR of C9orf72
303
Which diseases are associated with mutations in the 5’ UTR of C9orf72
ALS
| FTLD-TDP
304
Which of the FTLD genetically caused conditions are not also associated with ALS
Gene encoding progranulin
305
What is the result of mutations in the gene coding progranulin in FTLD-TDP
Loss of function at progranulin, which gets cleaved to help contain inflammation
306
Which morphology is strongly associated with FTLD-TDP
Presence of needle like NII’s and progranulin mutations
307
What is the general cause of Parkinson’s disease
Loss of dopaminergic neurons in the substantia nigra
308
What are the clinical symptoms of Parkinson Disease
Diminished facial expressions (aka masked facies), stooped posture, slowing of voluntary movement, festinating gait posture, rigidity and “pill rolling” tremor
309
What is the triad of Parkinsonism
Tremor, rigidity, and bradykinesia
310
Acute Parkinsonian syndrome with destruction of neurons in the substantia nigra can can be elicited by ingestion of which compound
MPTP with use of illegal meperidine
311
What is the diagnostic hallmark of Parkinson disease
Lewy body
312
What is the location of gene mutation in Parkinson Disease leading to alpha-synuclein aggregation
4q21
313
Where do Lewy bodies first appear in PD
Medulla and then ascend
314
In Parkinson Disease, what is the inheritance pattern of mitochondrial dysfunction
Autosomal recessive
315
Mitochondrial dysfunction in Parkinson Disease is assoacited wth mutations in genes coding which proteins
DJ-1
PINK1
Parkin
316
What is the inheritance of mutations in LRRK2 causing parkinson disease
Autosomal dominant
317
What is the mutation that causes autosomal dominant Parkinson disease
LRRK2
318
What is the characteristic finding of parkinson disease
- Pallor of the substantia nigra and locus ceruleus
| - Lewy body
319
What are the clinical presentations of progressive supranuclear palsy (PSP)
Parkinson Disease symptoms plus:
- truncal rigidity
- disequilibrium
- difficulty with voluntary eye movements
- Nuchal dystonia
- pseudobulbar palsy
320
What gender is at a higher risk for developing progressive supranuclear palsy
Men 2x likely
321
What is a pathological hallmark of progressive suprafacial palsy
Tau-containing inclusions in neurons and glia
322
What are the symptoms of corticobasal degeneration (CBD)
Parkinson disease symptoms plus:
- extrapyramidal rigidity
- jerking of limbs
- impaired higher cortical function (aka apraxia)
323
How is CBD and PSP differentiated from one another in the location of tau
CBD-cerebral cortical
| PSP-brainstem and deep grey matter
324
What are the morphological features of corticobasal degeneration
- “Ballooned” neurons (aka neuronal achromatia)
- Atrophy of motor and premotor
- Severe loss of neurons and gliosis
325
What is multiple system atrophy (MSA) characterized by
Cytoplasmic inclusions of alpha-synuclein in oligodendrocytes
326
What distinguished multiple system atrophy (MSA) from other neurodegerative diseases
Observed in glial cells and degeneration of white matter tracts without the presence of inclusions in neurons
327
What are the three tracts involved in Multiple System Atropy (MSA) and the result f their degeneration.
1-striatonigral circuit (Parkinsonism)
2-olivopontocerebellar circuit (ataxia)
3- ANS (orthostatic hypotension)
328
What is the hereditarabilty of Huntington disease
Autosomal dominant
329
What are the classical presentation signs for Huntington disease
Progressive movement disorders and dementia
330
What is the general cause of Huntington disease
Degeneration of striatal neurons
331
What are the repeats seen in Huntington Disease
CAG repeats coding for a poly glut sequence
332
What is the location and name of the gene associated with Huntington Disease
Huntington protein coded by HTT on chromosome 4p16.3
333
When is the repeat sequence in Huntington Disease usually occuring and what is the term used for it
Anticipation- repeat sequence is expanded during spermatogenesis, so the onset is early
334
What is the morphology of the brain in Huntington Disease
Brain is small and shows atrophy of the striatal neurons in the caudate nucleus and frontal lobe
335
What is the direction of pathological changes seen in Huntington disease
Medial to lateral in caudate
| Dorsal to ventral in putamen
336
Which set of neurons are especially prone to injury in Huntington Disease
Medium sized spiny neurons that primarily use gamma-aminobutyric acid at the NT, but also enkephalin, dynorphin, and substance P
337
Which set of neurons seem to be spared in Huntington Disease
- diaphorase positive neurons with nitric oxide synthase
| - large cholinesterase-positive neurons
338
What is choreoathetosis
Increased motor output leading to jerky movements
339
What aspect of Huntington disease is associated with CAG repeats
The onset of the disease, so the longer the sequence the early the disease onset
340
Patients with Huntington disease have a higher risk of which condition
Suicidal thoughts
341
What are the heritability of spinocerebellar ataxias (SBA)
Autosomal dominant
342
What are the spinal cerebellar ataxias associated with poly glutamate (CAG) repeats
1,2,3 (machado-Jones disease), 6,7 (includes visual impairment), 17, dentatorubropallidoluysian atrophy (DRPLA)
343
What are the spinocerebellar ataxias associated with expansion of non coding region repeats
8,10,12,31,36
344
What is the heritability of Fredreich Ataxia
Autosomal recessive
345
What are the general clinical presentations of Friedreich ataxia
Progressive ataxia, spasticity, weakness, sensory neuropathy, and cadiomyopathy,
346
What disease is charactertized by gait ataxia, followed by hand clumsiness and dysarthria in the first decade of life. Loss of deep tendon reflexes (extensor plantar reflex present). Loss of joint position and vibration sense.
Fredreich ataxia
347
In Fredreich ataxia, what is the effect on reflexes
Deep tendon are lost, but extensor plantar remains
348
Most individuals with friedrich ataxia develop which conditions
Pes cavus
| Kyphoscoliosis
349
What is the relation of friedreich ataxia and CV
Increased risk of cardiomyopathy with arrhythmias and congestive heart failure. Heart may be large with pericardial adhesions
350
What is the cause of Fredreich ataxia
GAA trinucleotide repeat in the first intron on chromosome 9q13
351
Which protein is mutated in Friedreich ataxia and what is its function
-frataxin which assembles iron into complex 1 and 2
352
What are the morphological findings in Friedreich ataxia
Loss of axons and gliosis in posterior columns, corticospinal tracts and spinocerebellar tracts
353
Which neuron are degenerated in friedreich ataxia
- Spinal column (Clarke column)
- brain stem (CN 8,10,12)
- cerebellum (dentate nucleus)
- Betz cells of motor cortex
354
What is the inheritabilty of ataxia-telangiectasia
Autosomal recessive
355
What are the clinical symptoms of ataxia-telangiectasia
Early in childhood, shows ataxia/dyskenetic Syndrome, followed by telangiectasia of conjunctiva and skin, along with immunodeficiency
356
What is the protein mutated in ataxia-telangiectasia and what is its location
Ataxia-telangiectasia mutated (ATM) on 11q22-q23
357
What is the role of ataxia-telangiectasia mutated (ATM) gene
Codes a protein used in fixing double stranded DNA breaks
358
Which disease shows enlargement of nucleases to 2 to 5 times the size (aka amphicytes), while the LNs, thymus and gonads are hypoplastic
Ataxia-telangiectasia
359
What is generally the first symptom in patients with ataxia-telangiectsia
Recurrent sinopulmonary infections (due to immunosuppression) and unsteadiness in gait
360
Which condition is normally developed in ataxia-telangiastia
Lymphoid neoplasms, in particular T cell leukemias
361
What is the pathogenesis of amyotrophic lateral sclerosis (ALS)
Loss of upper and lower motor neurons in the cerebral cortex with evidence of protein accumulation
362
What is the inheritability of amyotrophic lateral sclerosis (ALS)
Autosomal dominant
363
What is the most common form of amyotrophic lateral sclerosis
A4V mutation
364
What is the characteristic course of illness in the most common form of amyotrophic lateral sclerosis
A4V mutation with rapid and rarely involvement of upper motor neurons
365
Which mutation commonly gives rise to ALS and FTLD
C9orf72
366
What is the morphology seen in ALS
Anterior roots in spinal cord are atrophied due to loss of lower motor nerves
367
Which disease contains Bunina bodies, which are remnants of autophagy vacuoles
ALS
368
What is the result of losing upper motor neurons in ALS
Loss of the corticospinal tracts
369
What are the early symptoms seen in amyotrophic lateral sclerosis
Weakness of hands (dropping things), cramping/spasticity of arms and legs
370
What is the commonly recurring infection and what is the cause
Recurrent pulmonary infections due to loss of respiratory muscles
371
What is progressive musclular atrophy
Uncommon ALS cases that have lower motor neurons predominating
372
What is primary lateral sclerosis
ALS cases where the upper motor neurons predominate
373
What are the last motor neurons that are involved in ALS
Ocular eye motor neurons
374
What is progressive bulbar palsy
Aka bulbar ALS
| -degeneration of the lower brainstem Cranial motor nerves early and very rapidly
375
What is the name of Kennedy Disease
Aka spinal and bulbar Muscular Atrophy
376
What is the clinical presentation of Kennedy disease
Distal limb amyotrophy and bulbar signs, such as atrophy of the tongue and dysphasia
-Androgen insensitivity
377
What is commonly seen as the result of the androgen insensitivity seen in Kennedy Disease
- gynecomastia
- testicular atrophy
- oligospermia
378
What is Kennedy Disease caused by
X linked poly Glutamine repeats
379
What are the clinical presentations of spinal muscular atrophy
Marked loss of lower motor neurons resulting in progressive weakness
380
What is the most severe type of spinal muscular atrophy
SMA type 1, aka Werdnig-Hoffman disease
381
What is the course of illness with Type 1 SMA
Onset within the first year and death within 2
382
What is the course of illness in Type 3 SMA
Aka Kugelberg-Welander disease
| -Presents in late childhood or adolescence with motor disabilities
383
What is the severity of spinal muscle atrophy related to
The level of SMN protein on chromosome 5q
384
What is the function of the SMN protein that correlates with SMA
Assembly of the spliceosome
385
What is the inheritability of neuronal storage diseases
Autosomal recessive
386
What are the enzyme mutations unable to do in neuronal storage diseases
Catabolize:
- sphongolipids
- mucopolysaccharides
- mucolipids
387
In neuronal storage diseases, what is usually accumulating in the cell
The missing enzyme’s substrate
388
What are leukodystrophies
Mutations in genes that code for enzymes that are involved in the myelin synthesis or catabolism
389
What is the inheritability of leukodystrophies
Autosomal recessive
390
What is the general result of leukodystrophies
White matter deterioration leading to ataxia, loss of motor, spasticity, hypotonia
391
Which portion of the brain is more affected by defects in mitochondria
Grey matter (due to high ATP in neurons)
392
What are the general results from neuronal storage diseases
Loss of cognitive function and seizures
393
What are certified lipofuscinoses
Disorders in which lipid pigments accumulate in neurons
394
What is the result of ceroid lipofuscinoses
Blindness, cognitive and motor deteriation, and seizures
395
What relative age groups are prone to leukodystrophies
Younger ages
396
Which genetic metabolic disease does Krabbe disease fall under
Leukodystrophies
397
What is the inheritability of Krabbe disease
Autosomal recessive
398
What is the enzyme causing Krabbe disease
Deficiency in galactocerebroside Beta-galactosidase (aka galactosylcerimidase)
399
What product building up in Krabbe disease
Galactocerebroside is not proven down, so shunted into the toxic form of galactosylsphingosine
400
What is the clinical presentation of Krabbe disease
Rapid progression of motor signs of stiffness and weakness
401
When does Krabbe disease present and what is the survival rate
Presents between 3 and 6 month, leads to death by age 2
402
What does the brain morphologically look like in Krabbe disease
Loss of myelin and oligodendrocytes in the CNS and peripheral nerves
403
What is the diagnostic feature of Krabbe disease
Engorged macrophages (aka globose cells) in the brain parenchyma and blood vessels
404
What is the inheritability of metachromatic leukodystrophy
Autosomal recessive
405
What is the deficiency in metachromatic leukodystrophy
Lysosomal enzyme arylsulfatase A
406
What is the product building up in metachromatic leukodystrophy
Sulfatides, especially cerebroside sulfate
407
What is the pathology of metachromatic leukodystrophy
Sulfatides build up, leading to inhibition of oligodendrocyte differentiation, also eliciting an immuno response from the microglia
408
Histologically, what is diagnostic about metachromatic leukodystrophy
Macrophages with vacuolated cytoplasms that are scattered in the white matter and contain crystalloid structures composed of sulfatides
409
What is the inheritability of Adrenoleukodystrophy
X linked recessive
410
What mutation is associated with Adrenoleukodystrophy
ABC protein D1 (aka ABCD1)
411
What is the result of the mutation seen in Adrenoleukodystrophy
Loss of ABCD1, which transports molecules into the peroxisome
412
What is the pathology of Adrenoleukodystrophy
Inability to catabolism very long chain fatty acids (VLCFA) within the peroxisomes
413
What are the clinical presentations of Adrenoleukodystrophy seen in males
Progressive loss of myelin and adrenal insufficiency (atrophy of adrenal cortex)
414
What is adrenomyeloneurophathy
Allergic disorder in adults with progressive peripheral nerve disorder
415
What is the mutation seen in Pelizaeus-Merzbacher disease
Myelin formation proteins
416
What is the mutation seen in Alexander disease
GFAP
417
What is the mutation in vanishing white matter leukoencephalopathy
elF2B
418
What is the condition of heteroplasmy
Mixture of normal and abnormal mitochondria
419
In mitochondrial disorders, what can usually be seen
CNS targets damage in neurons and grey matter
Increased lactate levels
Decreased cytochrome C oxidase
420
What are the clinical presentation of Mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS)
- Recurrent episodes of acute neurological function
- Cognitive changes
- Muscle weakness
- lactic acidosis
421
The stoke like effects seen with MELAS are irreversible or reversible
Reversible
422
What is the most common mutation observed in MELAS
Gene encoding mito tRNA leucine (MTTL1)
423
How is Myoclonic epilepsy and ragged red fibers (MERRE) transmitted
Maternally
424
What are the clinical symptoms of Myoclonic epilepsy and ragged red fibers (MERRE)
Myoclonus, seizures, and myopathy (with red ragged muscle fibers), ataxia
425
What is the mutation causing Myoclonic epilepsy and ragged red fibers (MERRE)
tRNA other than Leucine
426
What is the age usually affected with Leigh syndrome
Infancy, most die within 1 to 2 years
427
What are the clinical symptoms of Leigh syndrome
Lactic acidemia, loss of psychomotor development, feeding issues, seizures, extraocular palsy, weakness with hypotonia
428
What are the histological findings in Leigh syndrome
Spongiform appearance with proliferation of blood vessels
429
What is the cause of Wernicke encephalopathy
Thiamine deficiency
430
What is the prognosis of Wernicke encephalopathy
Reversible if given thiamine shortly after signs
431
What are the clinal presentations of Wernicke encephalopathy
Acute psychomotor and ophthalmoplegia symptoms
432
What is the cause of Korsakoff syndrome
Bilateral destruction of the mammillary bodies
433
What is the clinical presentation of Korsakoff syndrome
Loss of short term memory and confabulation
434
What vitamin deficiency can lead to Korsakoff syndrome
Thiamine
435
Which conditions can predispose a patient to Korsakoff syndrome
Gastric disorders, carcinomas, chronic gastritis, or persistent vomiting (anything that decreases absorption)
436
Lesions on which area of the brain seem to correlate best with memory disturbance seen in Korsakoff syndrome
Dorsomedial nucleus of the thalamus
437
What is the cause of subacute combined degeneration of the spinal cord
Vitamin B12
438
What are the lesions in subacute combined degeneration of the spinal cord due to
Defect in myelin formation due to a lack of B12
439
What are the clinical symptoms of subacute combined degeneration of the spinal cord
Bilateral symmetrical numbness, tingling, and ataxia of lower extremities
440
How does the lesion in subacute combined degeneration of the spinal cord differ in early compared to late
Starts out at the mid thoracic level, but then spreads to the distal ends of both the ascending and descending tracts
441
Which regions of the brain are prone to damage due to hypoglycemia
Large pyramidal neurons in the cerebral cortex
| CA1 in the hippocampus
442
What are the changes seen in the brain as a result of hepatic failure
Astrocytes with enlarged nuclei and minimal cytoplasm (aka Alzheimer type 2 cells) appear in the cerebral cortex and basal ganglia
443
How does carbon monoxide cause damage to the brain
CO binds to the heme in cytochrome C oxidase
444
What area of the brain is prone to damage by carbon monoxide
-Kayers 3 and 5 of the cerebral cortex, Sommer sector of hippocampus
445
What is the affect of methanol on the brain
Causes retinal ganglion cells to degenerate and cause blindness
446
What part of the brain is affected by chronic alcohol use
Vermis of the cerebellum
447
Where do the majority of childhood CNS tumors arise and what is the percent
70% in posterior fossa
448
Where do the majority of adult CNS tumors arise and what is the percent
70% in the cerebral hemispheres above tentorium
449
What are the most common group of brain tumors
Gliomas (includes astrocytes, oligodendrocytes and ependymomas)
450
What is the most common primary brain tumor in adults and what is the percentage
Infiltrating astrocytomas (80%)
451
Where do most of the astrocytomas occur
The cerebral hemispheres
452
What are the common clinical presentations of infiltrating astrocytomas
Seizures, headaches, focal neuro defects at site of infiltration
453
What grade are diffuse astrocytomas
2/4
454
What grade are anaplastic astrocytomas
3/4
455
What grade are glioblastomas
4/4
456
What are the mutations seen in the classic subtype glioblastoma
- PTEN
- deletions of chromosome 10
- Amplification of EGFR
- 9.21 (CDKNA —> p16/INK4a)
457
What mutations are seen with proneural type of glioblastoma
- TP53
- isocitrate dehydrogenase genes (IDH1 and 2)
- upregulation of PDGRRA
458
What mutations are present in the neural type glioblastomas
NEFL
GABRA1
SYT1
SLC12A5
459
What mutations are seen in mesenchymal type glioblastomas
NF1 on chromosome 17
Decreased NF1
Increased TNF and NFKB
460
Which mutations are said to be present in the majority of primary glioblastomas
80-90%:
- activate RAS/PI3 kinase
- inactivate 53
461
In higher grade astrocytomas, what gene is assoacited with a better prognosis and which one with a worse prognosis
Good prognosis-mutated IDH1 (R123H)
| Bad prognosis-WT IDH1
462
What is the general prognosis with patients with a glioblastoma
Not very good
463
What age group does pilocytic astrocytomas generally occur
Children and young adults
464
What is the most common location for a pilocytic astrocytoma
cerebellum
465
What is the distinguishing feature of pilocytic astrocytoma from the other astrocytomas
Generally benign and tend to lack mutations in TP53
466
What is the location that pleomorphic xanthoastrocytoma is generally found
Temporal lobe of children/young adults
467
What is the distinguishing feature of pleomorphic xanthoastrocytoma
- abundant reticulum deposits
- chronic infiltration of inflammation
- absence of necrosis or mitotic activity
468
What is the grade of a pilocytic astrocytoma
Low (1/4)
469
What is the grade of pleomorphic xanthoastrocytoma
Lower (2/4)
470
What area of the brain is prone to oligodendroglioma
Cerebral hemispheres, especially the white matter
471
What are the most common mutations in oligodendrogliomas
Isocitrate dehydrogenase genes (IDH 1 and 2)-most
| Deletions of 1p and 19q
472
In oligodendrocytes, which combination of deletions is correlated with a better prognosis
Tumors with codeletions in 1p/19q, while loss of just one is chemo resistant
473
What are the characteristics of anaplastic oligodendrogliomas
High cell density, nuclear anaplasia, detectable mitotic activity, and necrosis
474
What is a common clinical symptom is seen in cerebral palsy
Choreoathetosis
475
What are ependymomas
Tumors arising next to the ependyma-lined ventricular system. Including the central canal of spinal cord
476
When do ependymomas occur in children, and what is the common location
In the first 2 decades of life, in the fourth ventricle
477
When do ependymomas occur in adults and what is the common location
Commonly seen in patients with neurofibromatosis type 2 (NF2) and seen in the spinal cord
478
What is the common location for an ependymoma if there is a mutation in chromosome 22
Spinal cord
479
What chromosome is commonly mutated if there is a ependymoma
22 (due to association with NF2)
480
Which tumors commonly for perivascular pseudorosettes
Aka tumor cells around vessels
| -Ependymoma
481
Expression of which gene is normally expressed in most ependymomas
GFAP
482
What is the location that myxopapillary ependymomas develop
Film terminale of the spinal cord
483
What is contained in the myxoid areas in myxopapillary ependymomas
Neutral and acidic mucopolysaccharides
484
What are the typical clinical location progression in ependymomas
Obstruction of the fourth ventricle commonly leading to hydrocephalus
485
Which location of ependymomas have the worst prognosis
Posterior fossa
486
What are the characteristics of the subependymomas
Slow growing nodules attached to ventricular lining and protrudes into the ventricle. Most commonly found in the lateral and fourth ventricle and are asymptomatic
487
Chorioid plexus papillomas most commonly occur in which patients
CHildren
488
What are the characteristics of the colloid cyst of the third ventricle
Non-neoplastic enlarging cyst in young adults. Causes noncommunicating hydrocephalus
489
What is the most common neuronal tumor of the CNS
Gangliogliomas
490
How do gangliogliomas typically present
Superficial lesions with seizures
491
Where are gangliogliomas commonly found
temporal lobe
492
Which tumor is said to have “floating neurons”
Dysembryopplastic neuroepithelial tumor
493
What is the most common poorly differentiated neoplasm
Medulloblastoma
494
What is the location and population where medulooblastomas are seen
Cerebellum in children
495
Which form of medulloblastoma has the best prognosis
WNT type
496
Which medulloblastoma group has the worst prognosis
Group 3
497
What are the characteristics of the WNT type of medduloblastoma
- Mutations in WNT
- monosomy of chromosome 6
- nuclear expression of Beta-catenin
498
What are the characteristics of the SHH type medulloblastoma
- Mutations in SHH
- modular desmoplastic histology
- MYCN amplification
499
Which patient group is WNT group medulloblastoma seen in
Older children
500
Which patient group is SHH group medulloblastoma seen in
Infants or young adults
501
Which patient group is group 3 medulloblastoma seen in
Infants and children
502
What are the characteristics of group 3 medulloblastoma
- MYC amplification
| - isochromosome i17q alteration
503
What are the characteristics of group 4 medulloblastoma
- chromosome i17q alterations
| - MYCN amplification
504
Which expression marker is found in most cells in medulloblastoma
Ki-67
505
Which condition causes formation of the HomerWright rosettes
Medulloblastoma
506
What does the medulloblastoma modular desmoplastic variant show
Stroma response marked with reticulum depositis forming “pale islands”
507
What does the medulloblastoma large cell variant show
Large nuclei, frequent mitosis and apoptosis
508
How do medulloblastomas normally disseminate
Through the CSF, such as to the cuada equina which is known as a “drop metastasis”
509
What is the prognosis of Atypical teratoid/Rhbdoid tumor
All before age 5 and survival is less than a year
510
What is the location and rate of spread in atypical teratoid/rhabdoid tumor
Malignancy in the posterior fossa and supratentrial compartments
511
What is the cause of atypical/rhabdoid tumors
Alterations in chromosome 22, in particular the hSNF5/INI1 coding for the INI1 protein
512
Which patient population are primary CNS lymphomas seen
AIDs patients
513
What are the characteristics of primary CNS tumors
- B cell lymphomas
- Multifocal, but rarely metastasize
- Rapid and aggressive
514
What is the morphological finding that is typical of a primary CNS Tumor
-Cells are separated from one another and form a “hooping” pattern
515
What is the location of primary brain germ cell tumors
Along the midline, commonly in the pineal and suprasellar regions
516
Which patient population is commonly affected by primary brain germ cell tumors
90% in first two decades
| -More common in Japan
517
Metastasis of which germ cell location is commonly seen in the CNS
Gonadal tumor referred to as a germinoma in the CHS
518
Which tumor markers will be found in the CSF during a germ cell tumor
- Alphafetoprotein
| - Beta-HCG
519
With regards to pineal parenchymal tumors, which form tends to affect children more
High grade tumors (aka pineoblastomas)
520
With regards to pineal parenchymal tumors, which form tends to affect adults more
Low grade tumors aka pineocytomas
521
How does the pineoblastoma commonly spread
Aggressively through the CSF space
522
What is the typical aggressiveness of meningiomas
Benign tumors
523
Where do meningiomas typically form
Meningothelial cells on the external surface of the brain, within the ventricular system and choroid plexus
524
What predisposes a patient to having a meningiomas
Prior radiation to the head and neck decades before
525
What is the typical mutation and gene affected meningiomas
Chromosome 22q with the gene NF2 coding for merlin
526
Which condition is commonly seen to have a meningioma
NF2
527
In meningiomas with NF2 mutations, what is the common mutation
TNF receptor assoacited factor 7 (TRAF7)
528
Which mutation is assoacited with higher graded meningiomas
NF2, loss of chromosome 22, and chromosome instability
529
What is the characteristic when meningiomas grow en plaqu
Sheetlike fashion over the dura
530
What are the characteristics that define an atypical meningioma
4 or more mitosis per higher power field microscopy or at least 3 atypical features
531
What histological finding is consistent with an atypical meningioma
Clear cell and chordoided
532
What is the aggressiveness of an anaplastic meningioma
Aggressive malignant sarcoma
533
What are the characteristics of the papillary meningiomas and rhabdoid meningiomas
High propensity to reoccur
534
Who is likely to get spinal meningiomas and what kind is it
10:1 females and are usually psommataous
535
What condition should be considered if meningiomas are present at multiple sites
Neurofibramatosis type 2
536
Which receptors are commonly expressed on meningiomas
Progesterone, so grow rapidly during pregnancy
537
What kind of cancer is the most common metastatic lesion in the brain
Carcinomas
538
What are the five kind of primary sites of metastatic lesions in the brain
- lung
- Breast
- melanoma
- kidney
- GI
539
What are paraneoplastic syndromes
Immune response against tumor antigens that cross react to the CNS
540
Subacute cerebellar degeneration is associated with damage of which cells
Purkinje cells, gliosis and mild chronic inflammatory cells
541
Which antibodies are present in subacute cerebellar degeneration
PCA1, which cross reacts with purkinje cells
542
What population does subacute cerebellar degeneration occur
Women with ovarian, uterine, and breast carcinomas
543
What does limbic encephalitis usually cause in the case of a physician
Search for a malignancy somewhere else
544
What does the ANNA-1 antibody in limbic encephalitis cross react with
Neuronal nuclei
545
Which tumor is ANNA-1 antibody assoacited with
Small cell carcinoma
546
What antibodies are associated with limbic encephalitis
ANNA-1
NMDA
VGKC complex
547
What does the NMDA antibody in limbic encephalitis cross react with
Hippocampal neurons
548
Which tumor is associated with the NMDA antibody
Ovarian tertomas
549
What does the VGKC antibody in limbic encephalitis cross react with
Aka voltage gated potassium channel in peripheral nervous system
550
Eye movement disorders, especially opsoclonus, are associated with which tumor
Neuroblastoma
551
Cowden syndrome is associated with which mutation
PTEN mutation affecting PI3K pathway
552
Li-Fraumeni Syndrome is associated with which mutations
TP53
553
Which tumor is Chowdrey syndrome associated with
Dysplasia gangliogliocytoma
554
Which tumor is Li-fraumeni associated with
Medulloblastomas
555
What tumor is turbot syndrome associated with
Medulloblastomas
556
Which mutation is seen in Turcot syndrome
APC
557
Which tumor is associated with Gorlin syndrome
Medulloblastoma
558
Which mutation is associated with Gorlin syndrome
Mutations in PTCH gene
