Chapter 28: Demyelinating/Neurodegenerative Diseases/Toxic and Acquired Metabolic Diseases Flashcards
1
Q
Demyelinating diseases of the CNS are acquired conditions characterized by preferential damage to ________ w/ relative preservation of ______.
A
Demyelinating diseases of the CNS are acquired conditions characterized by preferential damage to myelin w/ relative preservation of axons.
2
Q
Why is severe cognitive impairment not a usual feature of MS?
A
Gray matter is relatively spared
3
Q
Which disease is characterized by distinct episodes of neuro deficits separated in time due to white matter lesion that are separated in space
A
Multiple Sclerosis
4
Q
Which MHC halotype increases risk for developing MS?
A
HLA-DR2
5
Q
Which T cells are the major players in causing damage to the myelin in persons w/ MS?
A
CD4+ TH1 and TH17
6
Q
Which demyelinating disease is associated with lesions that are firmer than the surrounding white matter and contain circumscribed, depressed, glassy, grey-tan, irregularly shaped plaques?
A
MS
7
Q
What is seen morphologically in an active plaque of a patient with MS?
A
- Abundant macrophagescontaininglipid-rich, PAS-positive debris
- Perivascular (small veins) inflammatory infiltrate (mononuclear) at outer edge of plaqe
- Relative preservation of axons within plaque and depletion of oligodendrocytes
8
Q
A 40 yo woman who presents with chief complaint of unilateral disturbance should raise red flags for which disease until proven otherwise?
A
MS
9
Q
What is a frequent initial manifestation of MS?
A
Unilateral visual disturbances due to involvement of the optic nerve (optic neuritis, retrobulbar neuritis)
10
Q
The mnemonic for MS is SINS, what are each of these clinical findings?
A
S = scanning speech
I = intention tremor (incontinence and INO)
N = nystagmus
11
Q
Internculear opthalmoplegia (INO) often seen in MS is due to damage to what?
A
Medial longitudinal fasciculus (MLF)
12
Q
Which Ig is found in increased levels in the CSF of patients with MS?
What is seen on immunoelectrophoresis?
A
- IgG
- Oligoclonal IgG bands
13
Q
Infarction of which artery is associated with contralateral homonymous hemianopia?
A
Posterior Cerebral Artery
14
Q
Infarction of which artery is associated with UMN-type weakness and cortical-type sensory loss; contralateral hemiplegia initially?
A
Anterior Cerebral Artery (ACA)
15
Q
What is the significance of Transient Ischemic Attacks (TIA)?
A
- Are a warning sign for potentially larger ischemic injury to the brain
- Neurological emergency!
- 15% of TIA pts will have a stroke causing persistent deficits within 3 months; HALF of those within the first 48 hrs
16
Q
Genes for which interleukin receptors have been associated with an increased risk in developing MS?
A
IL-2 and IL-7
17
Q
What are the CSF findings in MS?
A
- Midly elevated protein
- Moderate pleocytosis in 1/3 cases
- IgG increased
18
Q
Which condition is characterize by synchronous bilateral optic neuritis and spinal cord demyelination?
A
Neuromyelitis optica (aka Devic disease)
19
Q
Neuromyelitis optica is due to antibodies against?
Major channel of which cell?
A
Aquaporin-4; major water channel of astrocytes
20
Q
What is commonly found in the CSF of patients with Neuromyelitis Optica?
A
White cells, often including neutrophils
21
Q
Although similar to MS, how does Acute Disseminated Encephalomyelitis (ADEM) differ?
When does it occur and what are the clinical manifestations?
A
- Occurs in younger patients w/ an abrupt onset and may be rapidly fatal
- Is a DIFFUSE monophasic demyelinating disease occuring after a viral infection or viral immunization (rare)
- Signs and symptoms develop 1-2 weeks after the antecedent infection as headache, lethargy, and coma
- In contrast to MS, all of the lesions look similar – monophasic
*MS has focal findings w/ considerable variance in the size of lesions
22
Q
Acute necrotizing hemorrhagic encephalomyelitis (AKA acute hemorrhagic leukoencephalitis of Weston Hurst) is almost invariable preceded by a recent episode of?
Who is most at risk?
A
- Upper respiratory infection (URI)
- Young adults and children
23
Q
Central pontine myelinolysis (aka osmotic demyelination disorder) most commonly arises when?
A
- 2-6 days after rapid correction of hyponatremia
- Low to high, the pons will die
24
Q
Which neurodegenerative disorder is characterized by loss of myelin in a roughly symmetric pattern involving the basis pontis and portions of the pontine tegmentum, including myelin loss WITHOUT evidence of inflammation?
A
Central pontine myelinolysis (aka osmotic demyelination disorder)
25
What is the clinical presentation of Central pontine myelinolysis (aka osmotic demyelination disorder)?
- Rapidly evolving quadriplegia, which may be fatal
- **"Locked-in" syndrome**, in which patients are fully conscious yet unresponsive
26
Following cleavage of APP by either the α-secretase or β-secretase, what is the function of the γ-secreatse complex?
- Performs an intramembranous cleavage
- When paired with first cut by α-secretase, produces a **soluble fragment**
- When paired with β-secretase cleavage, it generates Aβ (highly prone to aggregation)
27
Which chromosome is the gene encoding APP located on and why is this significant?
- Chromosome 21
- Lies in the **down syndrome** region; patients with down syndrome usually develop Alzheimers around age 40
28
Generation of which peptide aggregates are the critical initiating event for the development of AD?
Aβ first and then tau
29
Plaques are deposits of aggregated ______ peptides in the \_\_\_\_\_\_\_
Tangles are aggregates of the ________ binding protein tau
Plaques are deposits of aggregated **Aβ peptides** in the **neuropil**
Tangles are aggregates of the **microtubule** binding protein tau
30
Which 3 diseases do Tau deposits appear in without the appearance of Aβ?
1) Frontotemporal lobar degeneration (Picks disease)
2) Progressive supranuclear palsy
3) Corticobasal degeneration
31
Which chromosome contains the ApoE locus?
Chromosome 19
32
A higher number of (plaques/tangles) correlates better with the degree of dementia seen in AD?
Number of **neurofibrillary tangles** correlates better with the degree of dementia
33
What are the focal spherical collections of dilated tortous neuritic processes (dystrophic neurites) around an **amyloid core** seen in AD?
How are they stained?
- Neuritic (senile) plaques
- Amyloid core can be stained w/ **congo red**; dominant component of amyloid core = Aβ
34
Grossly how does the brain of a patient with AD look; where are the effects most pronounced?
Which compensatory change is seen?
- Cortical atropy = widening of sulci, narrowing of gyri
- Most pronounced in: **frontal, temporal**, and **parietal lobes**
- Compensatory ventricular enlargement --\> **Hydrocephalus ex vacuo**
35
Which parts of the brain will contain neuritic (senile) plaques associated w/ AD?
Hippocampus, amygdala, and neocortex
36
Diffuse plaques seen in AD have **no** _____ and are predominantly made up of Aβ\_\_\_\_
Diffuse plaques seen in AD have **no** amyloid core and are predominantly made up of Aβ **42**
37
Neurofibrillary tangles are seen best with which stain?
**Bielschowsky stain (silver stain)**
38
How do neurofibrillary tangles appear in pyramidal neurons vs. in rounder cells?
- **Pyramidal** = elongated **"flame"** shape
- **Rounder** cells = **"globose;"** basket weave of fibers around nucleus
39
Structures of which lobe are involved earliest in the AD and are usually severely atrophied in the later stages?
**Medial temporal lobe**, including hippocampus, entorhinal cortex and amygdala
40
Neurofibrillary tangles are insoluble and apparently resistant to clearance in vivo, thus remaining visible in tissue sections as _______ or _______ tangles long after the death of the parent neuron.
**"Ghost"** or **"Tombstone"** tangles
41
What are Hirano Bodies and what is their major component?
- Elongated glassy eosinophilic bodies
- **Actin** = major component
42
Cerebral amyloid angiopathy (CAA) is an almost invariable accompaniment of \_\_\_\_\_\_\_
AD
43
The vasuclar amyloid seen in CAA is predominantly of which type?
Aβ**40**
44
What is typically the terminal event in a patient with AD?
Intercurrent disease, often **pneumonia**
45
How are Frontaltemporal Lobar Degenerations (FTLDs) distinguished from AD in term of clinical manifestations?
Changes in personality, behavior, and language come BEFORE changes in memory
46
Accumulation of what is seen in FTLD-tau?
- Accumulation of tau and NOT Aβ are characteristic
- Smooth contoured inclusions ---\> **Pick bodies**
47
FTLDs are one of the more common causes of?
**Early** onset dementia
48
What is the characteristic pattern of atrophy seen in Pick disease?
- **Asymmetric**, atrophy of the **frontal** and **temporal lobes** w/ sparing of the posterior 2/3 of superior temporal gyrus
- Reduction of gyri to a wafer-thin (**"knife-edge"**) appearance
49
What are Pick Cells vs. Pick Bodies?
How do Pick bodies stain?
- **Pick cells** = swollen cells
- **Pick bodies** = cytoplasmic, **round** to **oval**, filamentous inclusions that are weakly **basophilic** and stain strongly with **silver**
50
Some patients with clinically diagnosed FTLD have inclusions that contain \_\_\_\_\_\_, but DO NOT contain Tau
TDP-43
51
The most common genetic form of FTLD-TDP is the result of an expansion of a _________ repeat in the 5' UTR of \_\_\_\_\_\_\_\_
The most common genetic form of FTLD-TDP is the result of an expansion of a **hexanucleotide** repeat in the 5' UTR of **C9orf72**
52
In FTLD-TDP, there are inclusions containing TDP-43 which is both ______ and \_\_\_\_\_\_\_\_
In FTLD-TDP, there are inclusions containing TDP-43 which is both **phosphorylated** and **ubiquinated**
53
There is an extremely strong correlation between the presence of needle like neuronal intranuclear inclusions (NII) and which mutation causing FTLD-TDP?
Progranulin mutations
54
In the absence of a toxic or other known etiology the presumptive diagnosis of PD can be based on the presence of the central triad of parkinsonism, which includes?
How is this diagnosis confirmed?
1) Tremor
2) Rigidity
3) Bradykinesia
- Confirmed by symptomatic response to L-DOPA replacement therapy
55
Which compound previosuly found in elicit drugs was found to destroy neurons in the substantia nigra and cause an acute parkinsonian syndrome?
MPTP
56
What is a characteristic morpological finding in the substantia nigra and locus ceruleus of patients with PD?
Pallor (**loss of pigmentation**) of the substantia nigra and locus ceruleus
57
Clinical features of PD can be remembered with mnemonic TRAPS, which includes?
**T =** tremor ("pill rolling" tremor at rest)
**R =** rigidity
**A** = akinesia and bradykinesia
**P** = postural instability (stooped posture)
**S** = shuffling gait (festinating gait)
58
First gene to be identified as a cause of autosomal dominant PD encodes \_\_\_\_\_\_\_
α-synuclein
59
What is the diagnostic hallmark of PD and what is the major component of this diagnostic indicator?
**Lewy body;** major component is α-synuclein
60
Mutations in the gene encoding ______ are a more common cause of autosomal dominant PD
LRRK2 (leucine-rich repeat kinase 2)
61
Single or multiple **cytoplasmic, eosinophilic**, round to elongated inclusions that often have a **dense core** surrounded by a **pale halo** describes what feature found in PD?
Lewy Bodies
62
Dementia with Lewy Bodies has which characteristc features?
- Fluctuating course (cognition/alertness)
- **Hallucinations**
- Prominent frontal signs
\*Ha**Lewy**cinations
63
In dementia with lewy bodies there is depigmentation of the substantia nigra and locus ceruleus w/ relative preservation of which structures?
Cortex, hippocampus, and amygdala
64
What is Progressive Supranuclear Palsy and when is it commonly seen?
What is the prognosis?
- A **Tauopathy** (does not contain Aβ)
**-** Onset between **5th** and **7th** decades, with **males 2x more affected**
- Often **fatal** within **5-7 years**
65
What are the clinical features of Progressive Supranuclear Palsy (PSP)?
- **Trunchal rigidity**, disequilibrium w/ **frequent falls** and **difficulty w/ voluntary eye movements**
- Also can have: **nuchal dystonia**, pseudobulbar palsy, and a mild progressive dementia
66
In PSP there is widespread neuronal loss in what areas of the brain?
What type of tangles are found in these areas and what does ultrastructural analysis reveal?
- Globus pallidus, subthalamic nucleus, substantia nigra, colliculi, periaqueductal gray matter, and dentate nucleus of the cerebellum
- Contain **globose fibrillary tangles**
- Straight filaments composed of **4R tau**
67
What is the pathologic hallmark of PSP?
**Tau**-containing inclusion in **neurons** and **glia**
68
What type of hydrocephalus may be seen with AD?
Hydrocephalus ex vacuo
69
What are the inclusions found in the brain of patients who die of CTE?
Tau
70
What 2 brain inclusions are associated with Parkinsons Disease?
- Tau
- α-synuclein
71
Inclusions containing SOD1, TDP-43, and FUS are associated with that neurodegenerative disease?
ALS
72
Which disease has a clinical pattern noted to be Parkinsonian w/ abnormal eye movements?
Progressive Supranuclear Palsy (PSP)
73
The 2 loci identified as causes of the majority of early-onset familial AD encode what?
Presenilin-1 and Presenilin-2
74
Which disease is characterized by extrapyramidal rigidity, **asymmetric motor disturbances** (jerking movements of limbs), and imparied higher cortical functioning?
Corticobasal Degeneration (CBD)
75
Clusters of tau-positive processes around astrocytes ("astrocytic plaques") and the presence of tau-positive threads in gray and white matter are specific pathologic findings for which disease?
Corticobasal Degeneration (CBD)
76
Multiple System Atophy (MSA) is characterized by cytoplasmic inclusions of ________ in oligodendrocytes (**glial cells**)
Multiple System Atophy (MSA) is characterized by cytoplasmic inclusions of **α-synuclein** in oligodendrocytes
77
What are the 3 distinct neuroanatomic circuits commonly involved in MSA; what does disruption of each lead to?
1. **Striatonigral:** parkinsonism
2. **Olivopontocerebellar:** ataxia
3. **ANS:** autonomic dysf. w/ **orthostatic hypotension** as prominent component
78
What is the primary pathologic event occuring in MSA?
**Glial cytoplasmic inclusions** (aka α-synuclein inside of oligodendrocytes)
79
How are the diagnostic glial cell inclusions in MSA stained?
**Silver stain**; show glial inclusions mainly in oligodendrocytes containing α-synuclein and ubiquitin
80
What is the prognosis of Huntington Disease?
Relentlessly progressive and uniformly fatal, average course of 15 years
81
What chromosome is the *HTT* gene encoding the protein *huntingtin* found on?
Chromosome **4**p16.3
82
Huntington Disease is the prototype of?
Polyglutamine trinucleotide repeat expansion diseases (CAG)
83
Repeat expansions of CAG associated with Huntington Disease occur when?
Spermatogenesis; paternal transmission associated w/ early onset in next generation
84
In Huntington Disease there is striking atrophy of?
**Caudate nucleus**; globus pallidus may atrophy secondarily
85
What is the age of onset most commonly seen with Huntington Disease?
Fourth and fifth decades (30-50 yo)
86
Huntington Disease patients are at an increased risk of suicide, but the most common cause of death is?
Intercurrent infection
87
Which 2 spinocerebellar degeneration disorders are Autosomal Recessive?
1. Friedreich ataxia
2. Ataxia Telangiectasia
88
Friedreich ataxia is associated with what expansion?
**GAA** trinucleotide repeat of gene on **chromosome 9q13** that encodes ***frataxin***
89
When is the onset of Friedreich Ataxia and how does it manifest?
How do the symptoms progress and what do most affected individuals develop?
- **First decade** of life beginning with **gait ataxia**, followed by **hand clumsiness** and **dysarthria**
- DTRs are depressed or absent, but **extensor plantar reflex** is typically present
- Joint position and vibratory senses impaired
- Most will develop **pes cavus** and **kyphoscoliosis**
**- Cardiomyopathy** later in life associated w/ arrhythmia and CHF
90
Loss of axons and gliosis are seen where in Friedreich Ataxia?
- Posterior columns
- Corticospinal tracts
- Spinocerebellar tracts
91
How long do patients with Friedreich Ataxia live and what are common causes of death?
- Most patients are wheelchair-bound within 5 years and live to about 40-50 yo
- Intercurrent pulmonary infections and cardiac death = **cause of death**
92
Which chromosome is the mutated ATM gene associated with Ataxia-Telangiectasia located on?
Function of this gene?
- Chromosome **11**q22-q23
- Encodes kinase critical for repair of **double-stranded DNA breaks**
- Fails to remove cells with DNA damage
93
When is the onset of Ataxia-Telangiectasia?
What are the common symptoms?
- Ataxic-dyskinetic syndrome beginning in early **childhood** w/ **recurrent sinopulmonary infections** and **unsteadiness in walking**
- Later on, **dysarthria** and **eye movement abnormalities**
- Subsequent development of **telangiectasias** in the **conjunctiva** and **skin** along w/ **immunodeficiency**
94
What is the prognosis of Ataxia-Telangiectasia and how do most of these patients die?
- Relentlessly progressive --\> **death** early in **second decade**
- Many develop **lymphoid neoplasms** (often **T cell leukemias**), gliomas, and **carcinomas**
95
In which condition do various cells, including Schwann cells in DRG and peripheral nerves, endothelial cells, and pituicytes show **bizarre** enlargement of the nucleus to 2-5x normal size and are referred to as **amphicytes**?
Ataxia-Telangiectasia
96
What is the morphology of the LNs, thymus, and gonads in Ataxia-Telangiectasia?
Hypoplastic
97
Progressive disease marked by loss of UMN in cerebral cortex and LMNs in spinal cord and brainstem w/ evidence of toxic protein accumulation
Amyotrophic lateral sclerosis (ALS)
98
Which missense mutation and on what gene is the most common cause of ALS in the US?
**A4V** mutation of ***SOD1*** on chromosome **21**
99
What is the age of onset for ALS and the earliest symptoms?
Symptoms progress to?
- **Asymmetric weakness** of hands -- dropping objects + difficulty performing fine motor tasks
- **Cramping +** **spasticity** of the arms and legs
- Fasciculations
- Respiratory infections
100
Mutations in *SOD1* associated with ALS are loss or gain of function?
Leads to?
- **Gain** of function associate w/ **mutant SOD1 protein**
- Forms **aggregates**
101
What are characteristic morphological findings on the spinal cord and brain in ALS?
- Anterior roots are **thin**
- Reduction in **anterior horn neurons**
- Precentral motor gyrus in the cortex may be **atrophic**
102
What do the remaining neurons in ALS contain?
**PAS-positive** cytoplasmic inclusions called **Bunina bodies** (remnants of autophagic vacuoles)
103
What is progressive musclar atrophy vs. primary lateral sclerosis in terms of findings in patients w/ ALS?
- **Progressive muscular atrophy:** applied to uncommon cases where LMN involvement predominates
- **Primary lateral sclerosis**: cases where UMN involvement predominates
104
What is progressive bulbar palsy (Bublar ALS) associated with some patients with ALS?
Prognosis?
- Some pts will have degeneration of the **lower brainstem cranial motor nuclei** occuring early and rapidly progessing
- Problems with **deglutination** and **phonation dominate**; clinical course is inexorable during 1-2 year period; 50% alive at 2 years
105
Which cerebral disease is ALS most often associated with?
FTLD; most often w/ TDP-43 inclusions
106
Spinal and Bulbar Muscular Atrophy (Kennedy Disease) is due to what mutation?
**X-linked** polyglutamine repeat expansion in the **androgen receptor gene**
107
What are common findings of Spinal and Bulbar Muscular Atrophy (Kennedy Disease)?
- Distal limb amyotrophy and bulbar signs --\> **atrophy** and **fasciculations** of the **tongue** and **dysphagia**
- Androgen insensitivity, gynecomastia, testicular atrophy, and oligospermia
108
What is the most severe form w/ the earliest onset of Spinal Muscular Atrophy?
Onset and prognosis?
- SMA type 1, Werdnig-Hoffmann disease
- Onset during first year of life w/ death by 2
109
All forms of spinal muscular atrophy (SMA) are associated with what genetic mutation?
Common clinical course?
- Disruption of *SMN1* (usually deletion)
- Marked loss of **LMN** --\> progressive weakness
110
Increased levels of which toxic product are seen in Krabbe disease?
Galactosylsphingosine
111
When is the onset of Krabbe disease and what are the clinical findings?
- Between 3-6 months of age; rapidly progressive motor signs of **stiffness and weakness**
- Fatal by age 2
112
Aggregation of engorged macrophages called globoid cells is a diagnostic feature of which disease?
Krabbe disease
113
In Metachromatic Leukodystrophy there is an accumulation of what?
What does this accumulation lead to?
**Sulfatides** ---\> white matter injury, inhibiting differentiation of oligodendrocytes, inflammatory response from microglia and astrocytes
114
Metachromatic Leukodystrophy can be observed using what stain?
What is a sensitive method of establishing diagnosis?
- Toluidine blue
- Metachromatic material in the urine = sensitive
115
Which disease is characterized by the inability to catabolize VLCFAs and increased levels in the serum?
Adrenoleukodystrophy
116
Who is most commonly affected by Adrenoleukodystrophy?
What is the typical presentation?
- Young males
- Present w/ **behavioral changes** and **adrenal insufficiency**
117
What occurs in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS)?
- Episodes of **acute neuro dysf.**, cognitive changes, and evidence of **muscle involvement w/ weaknss and lactic acidosis**
- Stroke like episodes often associated w/ **reversible deficits**
118
The most common mutation in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) is in what?
Gene encoding **mitochondrial tRNA-leucine (MTTL1)**
119
What are the symptoms and classic findings in Myoclonic Epilepsy and Ragged Red Fibers (MERRF)?
- Myoclonus, a seziure disorder, and evidence of **myopathy**
- **Ataxia** due to neuronal loss in cerebellar system also common
- Characterized by **ragged red fibers** on muscle biopsy
120
How is Myoclonic Epilepsy and Ragged Red Fibers (MERRF) transmitted and what is due to mutation in what?
- Maternally transmitted disease (mitochondrial)
- Mutations in **tRNA**; distinct from MELAS
121
When is the onset of Leigh syndrome and what are the common signs/symptoms?
- Disease of **infancy -- mitochondrial encephalopathy**
- **Poor psychomotor development**
- Lactic acidemia, **feeding problems, SEIZURES**, and weakness w/ **hypotonia**
122
What is seen histologically in the brain tissue of an infant with Leigh Syndrome?
- Multifocal regions of destruction to brain tissue
- **SPONGIFORM appearance** w/ **vascular proliferation**
123
What is the underlying mutation that causes Leigh Syndrome?
Genetic mutation in one of the genes coding for enzymes in **oxidative phosphorylation pathway**
124
What are the signs of Wernicke encephalopathy; caused by?
How can it be alleviated?
- Thiamine (B1) deficiency
- Acute; psychotic symptoms or opthalmoplegia
- **May reverse w/ Thiamine**
125
What is Korsakoff syndrome and the main signs/symptoms?
Is damage reversible?
Caused by?
- Disturbances of **short term memory** and **confabulation**
- **Irreversible**
- **Thiamine deficiency --\>** Chronic alcohol; also gastric disorders (carcinoma), chronic gastritis or persistent vomiting
126
Wernicke encephalopathy is characterized by foci of hemorrhage and necrosis where?
With time there is infiltration by?
**- Mammillary bodies** and **walls** of the **3rd** and **4th ventricles**
- Hemosiderin-laden macrophages
127
B12 deficiency causes what?
**- Subacute** combined **degeneration** of the spinal cord --\> defect in **myelin formation**
- Degeneration of both **ascending** and **descending** spinal tracts
128
What are the initial signs/symptoms of B12 deficiency?
- Bilateral **symmetrical numbness, tingling,** and slight ataxia in the **lower extremities**
- May progress to include spastic weakness of the lower extremities
129
Glucose deprivation (hypoglycemia) initially causes selective injury to which areas of the brain?
- Large pyramidal neurons of cerebellar cortex
- Hippocampus; especially Sommer sector (CA1)
- Purkinje cells of the cerebellum
- If severe, **PSEUDOLAMINAR necrosis** of the cortex
130
What occurs to someone suffering from clinical hyperglycemia and what precautions must be taken clinically?
- Pt becomes **dehydrated** and develops confusion, stupor, and eventually coma
- Fluid depletion must be corrected **slowly**; otherwise, **severe cerebral edema** may follow
\***From high to low**, the brain may blow!
131
What type of response in the CNS accompanies hepatic encephalopathy?
Critical mediators?
Which cells appear in the basal ganglia and cerebral cortex?
- **Impaired liver function** accompanied by **glial response** in the CNS
- Mediators = **ELEVATED** **ammonia** levels as well as **proinflammatory cytokines**
- **Alzheimers type II cells**
132
Carbon monoxide poisoning causes selective injury to which areas of the CNS?
- **Layers III and V** of the **cerebral cortex**
- **Sommer sector** of hippocampus
- **Purkinje cells**
- **BILATERAL NECROSIS** of the **globus pallidus** may also occur
133
Methanol toxicity preferentially damages what structure?
Which structures in brain may be damaged?
- **Retina**
- Degeneration of **retinal ganglion cells** may cause blindess
- **Selective bilateral necrosis** of the **putamen**
134
1% of chronic alcoholics will develop a clinical syndrome with what findings?
- Truncal ataxia
- Unsteady gait
- Nystagmus
135
In chronic alcoholics who suffer from cerebellar dysfunction where is atrophy and loss of granule cells mainly seen?
Anterior vermis
136
What is Bergmann gliosis and who is it seen in?
- Advanced cases of chronic alcoholism
- Loss of purkinje cells and **proliferation of adjacent astrocytes = Bergmann gliosis**
137
What are the pathologic findings in the CNS following exposure to high doses of radiation (\>10 Gy)
- Large areas of **coagulative necrosis**, primairly in white matter, and adjacent **edema**
- Vessels will have **thickened walls** w/ **intramural fibrin-like material**
138
Radiation may induce tumors years after therpay, and include what 3 types?
- Sarcomas
- Gliomas
- Meningiomas
