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Glossary of Block VIII, Week I

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the cytoplasmic granularity found in neurons is called?
Nissl substance
what type of stains are used for the best visualizations of neurons?
silver-based stains
("Beil" stain, Bodian stain)
T/F: neurons have no regenerative capacity
True
under what conditions would a neuron undergo chromatolysis?
when the axon is severed
(chromatolysis = swelling of cell body)
a neurological rabies infection would have what microscopic neuronal manifestation?
inclusion bodies
describe the microscopic characteristics of ischemic change in a neuron
pyknotic nucleus
red cytoplasm
"red-dead neurons"
what occurs in chromatolysis and what are the microscopic characteristics of it?
chromatolysis - severing of axon
see an eccentric nucleus, ground glass cytoplasm
function of astrocytes?
transport substances from blood to CNS
useful stains that help us visualize astrocytes? (3)
PTAH
GFAP
immunostain
MC reaction of astrocytes to injury?
proliferation, cause gliosis (glial scar)
what is the "gemistocytic change" sometimes seen in neuronal injury?
astrocytes that are plump, round and have an abundant eosinophilic cytoplasm
when are Alzheimer's type II astrocytes seen and what do they look like?
seen in hepatic failure
swollen, bizarre nuclei
when are Rosenthal fibers seen?
in chronic gliosis
stain used to best see myelin?
luxol-fast blue
reaction of oligodendrocytes to injury?
most likely cell death with resulting myelin loss
where are ependymal cells found?
line the ventricular cavities and the neural tube
function of choroid plexus?
produces CSF by ultrafiltration
changes seen in the ependymal lining when there is underlying astrocytic proliferation going on?
ependymal granulations
describe the ependymal cell
ciliated cuboidal epithelial cell
function of microglial cells?
specialized CNS macrophages
what is the stimulus for transformation of microglial cells to "rod cells?"
injury causes proliferation of microglial cells with elongation of nuclei = rod cells
what reaction does a microglial cell have to a virally infected neuron?
attacks it
how does a microglial cell become a foamy macrophage?
it scavenges lipid in infarcted and demyelinated areas
what stain is used to best visualize lipid-laden microglial cells?
oil-red-O stain
(orange is the lipid scavenged by the macrophages)
what are the four horizontal levels of a neuropathological lesion?
1. supratentorial
2. posterior fossa
3. spinal
4. peripheral
what are the 4 basic differentiations we should make in the clinic to evaluate a neurological problem?
1. anatomic level of lesion
2. focal or diffuse
3. progressive or nonprogressive
4. acute, subacute, chronic
most acute neuropathological incidents are of what etiology?
vascular
give an example of a focal, acute neuropathological incident
infarct
intraparenchymal hemorrhage
most subacute neuropathological incidents are of what etiology?
inflammatory
give an example of an acute, diffuse, neuropathological incident
subarachnoid hemorrhage
anoxia
give an example of a focal, subacute neuropathological etiology
abscess
give an example of a diffuse, subacute neuropathological etiology
meningitis or encephalitis
what is the most likely etiology of chronic, focal neuropathological symptoms?
neoplasm
what is the most likely etiology of chronic, diffuse neuropathological symptoms?
degenerative
what are the proposed mechanisms behind demyelinating disease? (3)
1. inflammatory (immune, autoimmune)
2. genetic
3. unknown
what type of demyelinating disease is characterized by a relapsing and remitting course?
MS
is MS characterized by focal or diffuse deficits?
focal
(distinct demyelinating lesions in the CNS)
when is the typical onset of MS?
3rd-4th decade
F:M of MS?
F:M = 2:1
what pathways are impaired in MS?
visual
sensory
motor
coordination
two types of MS?
1. classic (Charcot) form
- most common, classic relapsing and remitting course with gradual overall decline
2. acute (Marburg) form
- young adults, rapidly progressive and unrelenting course
MS is most apparent in what portion of the brain and spinal cord?
white matter
(in MS you see gray matter plaques in white matter areas)
what is a shadow plaque?
an older MS plaque that shows limited remyelination
microscopic characteristics of the axons in MS?
axons are relatively spared so they are most likely "normal" looking
where in the brain is it common for MS plaques to appear?
around the ventricles (esp. the lateral horns of the lateral ventricles)
describe the borders of an MS plaque
well circumscribed borders
describe the immune pathogenesis of MS that Dr. Weiland gave.
* oligodendrocyte injury mediated by cytotoxic CD4+ T-cells
* see oligoclonal immunoglobulins in the CSF
* lymphocytic infiltrates in the plaques
is there a genetic link for MS?
which HLA is MS associated with?
* increased risk in 1st degree relatives, increased in twins
* associated w/HLA-DR2
geographically, where is MS more common?
temperate zones
(risk conferred by 18 yrs of age)
which demyelinating disease is characterized by prominent visual and spinal cord involvement and NO cerebral or cerebellar involvement?
neuromyelitis optica (Devic's disease)
how can acute disseminated encephalomyelitis (ADEM) be distinguished from MS?
ADEM is a diffuse demyelinating autoimmune disease, MS is a focal demyelinating autoimmune disease
common etiologies of ADEM?
* often occurs after childhood viral illness (measles, rubella, VZV)
* vaccinations (rabies, mumps, rubella)
microscopic characteristics of ADEM?
perivascular inflammatory infiltrates with demyelination (seen in entire brain)
prognosis of ADEM?
variable, but most mild cases completely recover
describe acute hemorrhagic leukoencephalitis (AHL)
"hemorrhage with demyelination"
(a hyperacute form of ADEM with hemorrhage - often fatal within days)
micro characteristics of acute hemorrhagic leukoencephalitis? (4)
* perivascular demyelination
* inflammatory infiltrates
* fibrinoid necrosis
* punctate hemorrhages
symmetric non-inflammatory demyelination of the pons is known as?
central pontine myelinolysis
possible etiology of central pontine myelinolysis?
* hyperosmolality due to rapid overcorrection of hyponatremia
clinical features of central pontine myelinolysis?
ranges from asymptomatic to flaccid quadraplegia to stupor or coma.
leukodystrophies are hereditary disorders of?
myelin production or metabolism
metachromatic leukodystrophy is a defect in what enzyme? result?
defect in arylsulfatase A
*results in accumulation of sulfatides in oligodendrocytes
Krabbe disease is a defiency in?
beta-galactosidase
Adrenoleukodystrophy results in?
high levels of very long chain fatty acids
inheritance pattern of leukodystrophies?
AR
inheritance pattern of neuronal storage diseases?
AR
Tay-Sachs is a deficiency in?
hexosaminidase A
*result is accumulation of gangliosides
Hurler syndrome is a deficiency in?
a-iduronidase
* result is accumulation of mucopolysaccharides
Gaucher's disease is a deficiency in?
glucocerebrosidase
Neimann-Pick syndrome is a deficiency in?
sphingomyelinase
PKU is a deficiency in?
phenylalanine hydroxylase (get accumulation of phenylalanine=neurotoxin)
result of excess phenylalanine?
irreversible mental retardation, seizures
describe cretinism
congenital hypothyroidism
*see growth retardation, severe MR, deaf, mutism, motor spasticity/rigidity
neurological symptoms of Wilson's disease?
dystonia, tremor, ataxia
what is the location of CNS injury in wilson's disease?
basal ganglia (esp. putamen, caudate nucleus)
define spina bifida occulta
vertebral arch defect
describe a meningocele
cyst like protrusion of the meninges
describe a meningomyelocele
cyst like protrusion of the meninges with nerve roots and spinal cord elements. (neurological problems are common)
describe a rachischisis
complete failure of closure of the caudal end of the neuropore
describe anencephaly
failed closure of the anterior neuropore
describe Wernicke's encephalopathy
acute deficiency of thiamine (B1) - manifests as confusion, opthalmoplegia, altered temperature regulation. FATAL if untreated.
describe Korsakoff's syndrome
chronic deficiency of B1 (thiamine) - see antegrade amnesia, confabulation
in which thiamine deficiency are petechial lesions seen in the mammillary bodies?
Wernicke's
cardiovascular manifestations of a thiamine deficiency?
Beriberi heart disease
neurological manifestations of a B12 deficiency?
ataxia
(atrophy of posterior columns - position sense)
*sensory > motor deficits, dysesthesias common
which portion of the cerebellum is commonly atrophied in chronic alcoholism?
cerebellar vermis
besides atrophy of the cerebellar vermis, what other CNS changes are seen in relation to chronic alcoholism?
1. cortical atrophy
2. hydrocephalus-ex-vacuo (ventricles look larger due to cortical atrophy)
Parkinson's disease generally impairs voluntary or involuntary functions?
involuntary functions
what type of tremor is seen in PD?
resting
(may be absent in 1/4th of all PD patients)
avg. age of onset of PD?
45-60
PD involves a loss of?
DA neurons in the substantia nigra and locus ceruleus
what are Lewy bodies composed of?
a-synuclein
what characterizes parkinsonism-dementia complex of Guam?
parkinsonism w/ progressive dementia, death in 5-10 yrs
how does progressive supranuclear palsy (PSP) differ from PD?
PSP - no Lewy bodies, neuronal loss is in brainstem, basal ganglia, cerebellum
some possible etiologies of parkinsonism? (4)
1. post encephalitic
2. drug induced
3. toxin related (MPTP)
4. repeated head trauma
inheritance pattern of HD?
AD
describe the progression of HD
early cognitive and emotional impairment
* then, extrapyramidal symptoms (choreoathetosis)
*eventual incapacitation
gross pathology of a brain with HD?
atrophy of frontal cortex, striatum
* secondary lateral ventricle enlargement
HD involves a mutation in a gene on which chromosome?
chromosome 4
MC genetic mutation type seen in HD?
trinucleotide repeat expansion
ALS involves which neurons?
upper and lower MOTOR neurons
describe the clinical course of ALS
* progressive muscular weakness
* atrophy, cramps, fasciculations
* motor speech disturbance
* intellect intact
* death usually w/i 3-5 yrs
avg. age of onset of ALS?
40-60 yrs
gender differences in ALS?
M>F
familial ALS (5-10%) is related to a mutation in?
superoxide dismutase 1 gene (SOD1)
nervous system areas that atrophy in ALS?
* cortical motor neurons
* motor nuclei of brain stem
* loss of axons in LCST
* anterior horn spinal cord neurons
* anterior spinal nerve roots
which degenerative disease accounts for >50% of dementia
AD
characteristics of AD?
progressive dementia with memory and cognitive impairment
risk factors for AD? (3)
1. age
2. family history
3. female gender
what genetic disorder does AD have a strong connection to?
Down's syndrome (trisomy 21)
Four etiological factors that may contribute to AD?
1. amyloid beta
2. amyloid precursor protein
3. Apoprotein E e4
4. Presenilins
function of presenilins?
create amyloid protein from amyloid precursor protein (APP)
mutations in presenilins result in?
most cases of familial AD
which type of apolipoprotein has the lowest risk of AD?
ApoE e2 or 3
gross characteristics of AD?
*cortical atrophy (esp. frontal-parietal, temporal)
*atrophy of gyri, widening of sulci
* hydrocephalus ex vacuo
microscopic features of AD?
*neurofibrillary tangles
*neuritic plaques
*granulovascular degeneraton
*Hirano bodies
in AD, neurofibrillary tangles are primarily made up of what protein?
tau (microtubule associated protein)
in AD, what is found at the core of neuritic plaques?
amyloid
in AD, where is granulovascular degeneration found?
in the cytoplasm of hippocampal neurons
in AD, what are Hirano bodies?
eosinophilic bodies by hippocampal neurons (seen alongside granulovascular degeneration)
describe diffuse Lewy body disease
dementia with Lewy bodies, may have accompanying akinetic rigidity syndrome (Parkinson like)
gross characteristics of Lewy body dementia?
not much, relatively little atrophy
gross features of Pick's disease?
*marked cerebral atrophy limited to frontal and temporal lobes
*knife-blade gyri
what is a Pick body?

neurons with eosinophilic cytoplasmic inclusions
which stain is used to see Pick bodies?
silver stain
50% of dementia can be classified as?
AD
dementia in which a personality change or language disorder is seen is called?
frontotemporal dementia
(10% of all dementias)
what must be present in order to make the diagnosis of dementia?
acquired memory impairment WITH impairment in other domains (cognitive or social).
how common is dementia?
5-10% of community dwelling adults over the age of 65
50% of those over the age of 80.
70% of all nursing home pts.
how can a person have cognitive impairment but not meet the definition of dementia?
poor memory performance but NORMAL general cognition and ADLs
what are some "reversible" causes of dementia? (7)
1. depression
2. medication
3. alcohol use
4. delerium
5. chronic menigitis
6. tumor
7. normal pressure hydrocephalus
describe progressive pseudodementia
paitents describe cognitive complaints, have difficulty encoding memories.
DURATION OF DEMENTIA IS SHORTER, depression common, antidepressant trial often warranted
List 5 medications commonly responsible for cognitive decline
1. pain meds
2. anticholinergics (amitryptiline, nortryptaline)
3. antihypertensives
4. psychotropics
5. sedative-hypnotics (sleeping pills)
how common is true inherited AD?
<5%
mean survival of an AD patient?
8.1 years
MC cause of death in an AD patient?
pneumonia
physical manifestations of late AD?
increased tone,
myoclonus,
seizures,
bradykinesia,
incontinence,
dysphagia,
weight loss
psychiatric manifestations of AD?
depression
delusions
hallucinations
personality change
in which type of dementia are hallucinations very common?
Lewy body dementia
6 risk factors for AD?
1. Apo-E4-Allele
2. Family history
3. age
4. female
5. head injury
6. lower intelligence/smaller head size
two pharmacologic treatments of AD?
1. acetylcholinesterase inhibitors
2. NMDA antagonists (Namenda)
what is the second leading cause of dementia?
Vascular dementia
(single stroke, multi-infarct, subcortical arteriosclerotic encephalopathy)
what is it called when vascular dementia is mixed with Alzheimer's pathology?
mixed dementia
describe the classic onset of vascular dementia
sudden onset or stepwise deterioration
how can vascular dementia be diagnosed?
abnormal imaging studies
(also see focal neurological signs and stroke risk factors)
what types of strokes cause dementia?
lacunar strokes
strategically placed "normal" stroke
what does a white matter change indicate?
many things, SOMETIMES can indicate dementia and/or AD.
what is the 3rd cause of dementia?
subcortical arteriosclerotic encephalopathy (SAE), aka. Binswanger's disease
where is demyelination and gliosis seen in subcortical arteriosclerotic encephalopathy?
periventricular
3 psychological findings in SAE?
psychomotor retardation
apathy
abula (lack of initiative)
5 physical findings in SAE?
1. pseudobulbar brainstem signs (trouble swallowing)
2. hypperreflexia
3. upgoing toes
4. gait disturbance
5. incontinence
treatment for multi-stroke dementia? (4)
*antithrombotic
*cholinesterase inhibitors
*memantine
*supportive, risk factor management
avg. age of onset of frontotemporal dementias?
EARLY <65
three distinct pathologies of frontotemporal dementia?
1. Pick's disease
2. Frontal lobe degeneration
3. progressive subcortical gliosis
what is semantic dementia?
fluent empty speech "verbal diarrhea"
(loss of knowledge about items, trouble with naming, word comprehension. grammar and pronunciation remains intact)
what is progressive nonfluent aphasia?
nonfluent speech, progresses to muteness
describe the progression of CJD
subacute dementia with myoclonus, rapidly progressive
*80% dead in 1 yr, 50% dead w/i 5 mo.
avg age of onset of CJD?
50-75 yrs
pathogenesis of CJD?
prion protein (PRP - normally an a-helix) changes conformation to a beta-pleated sheet (bad form: protease resistant). this form accumulates in neuronal tissue, causes neuronal death.
7 classical signs/symptoms of Parkinsonism?
1. rigidity
2. bradykinesia
3. tremor
4. stooped posture
5. instability
6. changes in handwriting
7. sleep disorders
T/F: DBS helps parkinsonism
FALSE
DBS only helps PD, not all cases of Parkinsonism
PD makes up for what proportion of parkinsonism cases?
2/3
5 other causes of parkinsonism?
1. PSP (progressive supranuclear palsy)
2. MSA (Multi-system atrophy)
3. CBD (Corticobasal degeneration)
4. LBD (Lewy body disease)
5. stroke
others
which two races have the lowest incidence of PD?
Asians
African Americans
voice changes seen in PD?
hypophonia
(soft, tremulous voice)
what clues suggest a diagnosis OTHER than PD? (7)
1. lack of tremor
2. prominent/early dementia
3. autonomic dysfunction
4. early instability/falls
5. eye movement difficulties
6. lack of response to levodopa
7. early hallucinations
how many DA neurons must be lost before motor symptoms appear in PD and a diagnosis is made?
80%
how long before the onset of PD does loss of the DA neurons begin?
20-30 yrs prior
early symptoms of PD? (5)
1. anxiety, depression
2. changes in sense of smell
3. constipation
4. postural changes
5. sleep disorder/weight loss
in the on-off phenomenon, what does the off phase correspond to?
no DA stimulation
in a PD patient, what are the leading cognitive risk factors for nursing home placement?
delerium and dementia
three stages of PD?
1. honeymoon period
2. battle area
3. late phase
which type of PD is thought to have a better prognosis?
tremor predominant PD
which 2 types of PD are thought to have a prolonged course?
unilateral disease
young patients
gold standard treatment of PD?
Sinemet (carbidopa/levodopa)
MOA of carbidopa/levadopa?
*levadopa causes peripheral side effects (toxic)

*carbidopa counteracts these peripheral side effects (MAO inhibitor, blocks levodopa breakdown into toxins in periophery)
how can nausea be treated in the PD patient on carbidopa/levadopa?
increase carbidopa
take with meals
3 dopamine agonists used to treat PD?
1. Mirapex
2. Permax
3. Bromocriptine
neuroprotectant used to prevent progression of PD?
Selegeline
role of Entacapone (Comptan) in PD treatment?
extends 1/2 life of levadopa
3 anticholinergics used to treat PD?
1. Congentin
2. Artane
3. Benadryl
MOA of Amantadine?
NMDA antagonist
in DBS for PD, where are the electrodes placed (1 of 3 locations)
1. globus pallidus
2. subthalamic nucleus
3. thalamus
2 positive outcomes of surgery for PD?
1. improves time spent in "on" state
2. decreases need for meds
risks/negative outcomes of surgery for PD?
*risk of bleed, stroke, infx
*risk of masking dementia, dysarthria
*poor placement or equipment failure
characteristics of Lewy Body Dementia (DLBD) when it comes to meds?
very sensitive to meds & their adverse effects - treat gingerly
in which sex is DLBD more common?
males
MC of death in DLBD?
aspiration pneumonia
how long from symptoms to death in DLBD?
6.4 yrs
where are the Lewy Bodies found in DLBD?
dopaminergic neurons (diffusely located)
treatment of DLBD?
1. low dose carbidopa/levadopa
2. low dose antipsychotic for hallucinations (quetiapine or clozapine)
3. AChE inhibitor for cognition, behavior problems
4. Klonopin for periodic limb movements of sleep
hallmark symptom of progressive supranuclear palsy (PSP)?
supranuclear opthalmoplegia
does PSP respond to levadopa?
NO
avg age of onset of PSP?
60s-70s
regarding PSP: on average, how long after diagnosis does death occur?
6 yrs
Treatment for PSP? (3)
1. Sinemet - limited motor response
2. SSRIs (depression/anxiety, pseudobulbar effect)
3. AChEIs for dementia
3 variants of multiple system atrophy (MSA)?
1. Shy Drager syndrome (MSA-A)
2. striatonigral degeneration (MSA-B)
3. OPCA (MSA-C)
characteristics of MSA-A (Shy-Drager syndrome)?
dysautonomia (faining, cold hands, mottling, incontinence)
characteristics of striatonigral degeneration (MSA-B)?
Parkinsonian symptoms
characteristics of OPCA (MSA-C)
ataxia
treatment for MSA?
PT/Speech Therapy
early response to levadopa
fludrocortisone or midodrine for BP support
four causes of acquired ataxias?
1. alcohol
2. chemotherapy
3. infections
4. paraneoplastic
two inherited ataxias?
1. Friedreich's ataxia (AR)
2. Spinocerebellar ataxia (AD and sporatic)
what is the rarest Parkinsonian condition?
Corticobasal degeneration
age of onset of corticobasal degeneration?
60's or later
s/s of corticobasal degeneration?
"alien limb phenomenon"
asymmetric parkinsonism and limb dystonia WITH UMN signs and late dementia
"lower-half" parkinsonism with prominent gait disturbance, subcortical dementia, AND a history of stroke is called?
vascular parkinsonism
what is the cause of dementia pugulistica?
repeated head trauma
s/s of dementia pugilistica?
*attentional and memory deficits
*parkinsonism
is there any genetic group that is at higher risk of dementia pugilistica?
ApoE4 carriers
symptomatic, communicating, adult onset hydrocephalus is known as?
normal pressure hydrocephalus
what is the triad seen in normal pressure hydrocephalus?
1. subcortical dementia (subacute)
2. frontal "magnetic" gait disturbance
3. urinary incontinence
what is frequently seen in normal pressure hydrocephalus?
parkinsonism
(with bradykinesia, rigidity, limb tremors)
causes of normal pressure hydrocephalus? (3)
1. remote trauma, infection
2. subarachnoid hemorrhage
3. idiopathic
of the triad seen in normal pressure hydrocephalus, which symptom is earliest?
gait disturbance (apraxic gait - "stuck to floor" feeling)
MRI findings in NPH?
1. ventriculomegaly
2. thinning of corpus callosum
3. no CSF flow
shunting is what is normally done to treat normal pressure hydrocephalus. when is it less effective?
if small vessel disease is present
success rates/results of shunting in NPH?
1/3 have marked improvement
1/4 have mild improvement
1/4 have moderate complications
1/4 have shunt malfunction
describe an essential tremor
tremor that is most promiment with intention.
*often distal in the limb
which type of tremor, resting or essential, is responsive to alcohol?
essential
what am I?
hyperkinetic movements with irregular, unpredictable, brief, jerky movements that move from one part of the body to another...
chorea
what is the difference between chorea and choreoathetosis?
choreoathetosis is slower than the characteristically brisk chorea
what am I?
inherited, progressive disorder manifested by chorea and other movements, behavior disorder and dementia
HD
inheritence pattern of HD?
AD
when do s/s of HD appear?
in the 4th or 5th decade
where is the HD gene and what happens genetically in HD?
chromosome 4
HD is the result of an expanded CAG trinucleotide sequence
genetic correlation between severity of the disease?
increased number of repeats = increased severity of disease
under which type of inheritance is the number of repeats in HD more likely to increase?
father to child
what type of reflexes would most likely be present in a HD patient?
brisk reflexes
upgoing toes
what part of the brain atrophies in HD?
caudate
what is the life expectancy after an HD diagnosis?
10-20 yrs
MCC of death in HD?
aspiration
signifance of earlier onset HD as compared with "normal" onset?
earlier onset has faster progression and seizures are more likely
the condition of chronic dopamine receptor blockade is known as?
tardive dyskinesia
MC location of tardive dyskinesia?
around the face
(can occur in the body as well)
what disorder am I?
disorder of sustained muscle contraction which creates abnormal posture?
dystonia
generalized dystonia is often inherited. it is due to a mutation of?
the DYT1 gene
any treatment for dystonia?
dopamine
SOME are dopamine responsive, others are not
which type of dystonia often starts late in adult life?
focal or segmental
which sex is tics more common in?
males
age of onset of tics?
childhood
what is Tourette's syndrome?
childhood onset of motor and vocal tics
inheritance pattern of Tourette's syndrome (TS)?
AD
TS is commonly seen with what other conduct disorders? (2)
ADHD
OCD
which disorder am I?
sudden, brief, shock-like involuntary movements
myoclonus
myoclonus is seen in what brain diseases/injuries? (3)
1. hypoxic brain injury
2. late stage neurodegenerative diseases
3. early stage CJD
name three metabolic movement disorders with associated dementia
1. Wilsons disease
2. Hallevorden-Spatz
2. Idiopathic basal ganglia calcification
what is Hallevorden-Spatz disease?
early onset dementia with parkinsonism - iron deposition in basal ganglia
idiopathic basal ganglia calcification presents as?
dementia with parkinsonism
(familial disorder)
inheritance pattern of Wilsons disease?
AR

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