Central Nervous System Degenerative Diseases Flashcards
What characterizes a Neurodegenerative disease
- progress loss of neurons
- typically affecting groups of neurons with functional relationships even though they are not next to each other.
what is the pathologic process commonly seen in neurodegenerative diseases
accumulation of protein aggregates
Name 2 cerebrocortical Degenerations disease
Alzheimer disease
-frontotemporal lobar degenerations Picks disease
Alzheimer is a progressive loss of neurons where in the brain? what exactly happens? This process results in what?
- decreased choline acetyltransferase and acetylcholine in cerebral cortex
- Dementia
If a patient were to walk into the office, how would you diagnose them with Alzheimer disease
Clinical and brain imaging ID
-brain tissue for definitive diagnosis
pathogenesis
the manner of development of a disease
pathogenesis of Alzheimer disease
Amyloid precursor protein
- transmembrane
- can be cleaved to form ABeta peptide
What are 2 proteins associated with Alzheimer disease
ABeta 40 and 42
Tau
what are some general characteristics of Abeta peptide
- aggregates easily
- forms beta-pleated sheets of amyloid
- resistant to breakdown
- Neurotoxic
what can be stained to find ABeta
congo red
what are the abnormal chromosomes in Alzheimer
1, 14, 19, 21
what protein is on chromosome 21
Amyloid precursor protein
Besides Alzheimer disease being associated with chromosome 21, what other disease is associated with it ? When do people with this get Alzheimer
Down Syndrome
-3rd or 4th decade
What get mutated on chromosome 14 and 1 for Alzheimer
Chromosome 14: Presenilin 1
Chromosome 1: Presenilin 2
what happens when Presenilin 1 and Presenilin 2 get mutated in Alzheimer Disease
increases the amounts of Abeta peptide via gama-secretase complex
What protein is associated with chromosome 19
ApoE
What does ApoE E4 isoform promote
ABeta generation and deposition
4 brain morphology of Alzheimer disease
- atrophy of cerebral cortex
- Thinned Gyri and Widened Sulci
- Cortical Gray matter thinned
- dilation of lateral ventricles
Hydrocephalus ex vacuo
dilation of lateral ventricles
what are 3 things seen under the microscope for Alzheimer Disease
Neuritic plaques
Neurofibrillary tangles
cerebral amyloid angiopathy
what is in a neuritic plaque
central amyloid Abeta42 peptide core with clear halo
where in the brain are neuritic plaques found
hippocampus
amygdala
neocortex
spares: motor and sensory cortices
Another name for Bielschowsky stain
silver staining
what are nuerofibrillary tangles
bundles of filaments in cytoplasm
-paired helical filaments (tau)
what does Neurofibrillary tangles look like on a Silver stain? what type of cell are they found on?
flame-shaped in pyramidal neurons
What is cerebral amyloid angiopathy
deposition of amyloid Abeta40 in walls of small meningeal and cortical arteries
Gliosis
nonspecific reactive change of glial cells in response to damage to the central nervous system
what is the age group for Alzheimer Disease
greater than 50 years
what are the first subtle changes in Alzheimer disease
- loss of higher cortical function
- changes in mood and behavior
what are later clinical changes in Alzheimer disease
disorientation
memory loss
aphasia
aphasia
loss of ability to understand or express speech
can’t perform ADL’s
How is Alzheimer disease treated
some drugs can help with symptomatic improvement
-no treatment stops progression of disease
what is frontotemporal lobar degenerations
heterogeneous set of disorders associated with focal degeneration of frontal and/or temporal lobes
what age group does frontotemporal lobar degenerations hit
younger than 65 years of age
how is Frontotoemporal lobar degenerations distinguished from Alzheimer’s disease
alterations in personality, behavior, and language preceding dementia
what proteins are associated with frontotemporal lobar degenerations
tau or TDP43
FTLD-Tau is also called what
Pick disease
what age range does pick disease usually present
40-65 years
Where on the brain does Pick Disease usually occur? what areas are usually preserved?
- selective lobar atrophy of anterior frontal and temporal lobes ( knife-edge atrophy)
- posterior 2/3 of superior temporal gyrus, parietal and occipital lobes are preserved
In what layers of the brain are neurons lost in Pick Disease
outer 3 layers of cortex
Surviving neurons in Pick disease are called what and have what characteristics?
Pick bodies
- tau
Pick bodies usually occur where in the brain
cerebral cortex in cortical layer II
dentate gyrus of hippocampus
Name 3 basal ganglia degenerations
Parkinson disease
Parkinsonism
Huntington Disease
What happens in the brain in Parkinson disease
depigmentation neuronal loss gliosis of pigmented nuclei -damage pathway from substantia nigra to corpus striatum -decrease dopamine in corpus striatum
how are neurons lost in Parkinson disease
apoptosis or necrosis
what is the genetic link for Parkinson disease
mutation in gene for alpha-synuclein on chromosome 4q
-affect its folding/alter its structure
What would the gross pathology look like for Parkinson’s
depigmented substantia nigra and locus ceruleus
what are 3 things on microscopic level for Parkinson disease
- Lewy Body
- gliosis of substantia nigra and locus ceruleus
- loss of dopaminergic neurons
Lewy bodies also have what in them
melanin granules
After what age does Parkinson occur
after 50
what are some clinical features for Parkinsons
cog-wheel rigidity
- resting tremor
- Bradykinesia
- Gait, festinating
- slow, difficult speech
what are treatment options for Parkinsons
Pharaceuticals
deep brain stimulation
pallidotomy
what is the prognosis for Parkinsons disease
Poor
Patients with Parkinson disease also have what
dementia
hallucinations and frontal signs
where are lewy bodies found in brain
medulla
midbrain
cortex
what are 3 causes of Parkinsonism
Postencephalitic Parkinsonism - after Spanish influenza 1915-1918
- drug side-effect
- trauma
what drugs might cause Parkinsonism
Phenothiazines
reserpine
MPTP
How is Huntington Disease inherited
autosomal dominant
complete penetrance
delayed appearance
what gene and chromosome is messed up in Huntington disease
HD gene
short arm of chromosome 4
-CAG repeats
where do loss of neurons occur for Huntington disease
cuadate nucleus
putamen
variable cerebrocortical atrophy
at what age does Huntington present
20-50 years
what are symptoms of Huntington’s disease
dementia and psychotic
choreiform movements
what is correlated with an earlier onset of Huntington Disease
longer CAG repeats
Spinocerebellar degnerations usually occur where
cerebeullum, brainstem, spinal cord, peripheral nerves
Name a spinocerebellar degneration disease
Friedrich ataxia
How is Friedrich ataxia inherited? what goes wrong genetically?
autosoma recessive GAA repeat protein deficiency (Frataxin)
who usually gets Friedreich’s ataxia
late childhood/pre-adolescence
what goes wrong in Friedreich’s ataxia
degeneration of spinocerebellar tracts, posterior columns, pyramidal tract, peripheral nerves
what are clinical symptoms for Friedriech’s ataxia
pes cavus
kyphoscholiosis
Define motor neuron disease
degeneration of both upper and lower motor neurons
where does loss of upper motor neurons occur
cerebral Motor cortex
where does degeneration of corticospinal tracts occur
lateral spinal cord ( lateral sclerosis)
where does loss of lower motor neurons occur
brain stem and spinal cord ( anterior)
Name two motor neuron diseases
amyotrophic lateral scleriosis
spinal muscular atrophy
what does the gross anatomy look like for ALS
thinned ventral roots of spinal cord
what does ALS look like under a microscope
- upper motor neuron destruction leads to degeneration of myelin in corticospinal tract
- decrease neuron in anterior horn throughout length of spinal cord, loss of anterior root myelinated fibers
- skeletal muscles show neurogenic atrophy
What are clinical symptoms for ALS
- upper motor paralysis of extremities
- lower motor neuron signs
what are some upper motor signs for ALS
weakness - increased reflexes spasticity -pseuodbulbar - babinski sign
pseuodbulbar
Inappropriate involuntary laughing and crying due to a nervous system disorder
what are lower motor neuron sign for ALS
weakness decreased reflexes atrophy fasciculation muscle denervation
what gender is more prone to ALS? age?
men usually over 50
what is the prognosis for ALS
50% 5-year survivial
what is the usual cause of death for ALS
bronchopenumonia secondary to muscle paralysis
what used for treatment of ALS
symptomatic and riluzole ( glutamate antagonist)
Another name for Spinal muscular atrophy type 1
Werdnig-Hoffman disease
how is Werdnig-Hoffman disease inherited
autosomal recessive - deletions of survival motor neuron gene, chromosome 5
what goes wrong in Werdnig-Hoffman disease
- loss of motor neuron in anterior horn
- atrophy of anterior spinal roots and peripheral motor nerves
- denervation and atrophy of skeletal muscle groups
clinical presentation for spinal muscular atrophy
congenital hypotonia (“floppy baby”)
what is the most common autoimmune inflammatory, demyelinating disorder
Multiple sclerosis
what is MS
episodes of neurologic deficits separated in time, attributable to white matter lesions separated in space
-plaques in white matter ( adjacent to lateral ventricles, optic nerves, chiasm, brain stem, cerebellum, and spinal cord)
who is most likely to get MS
any age 20-40 most common
Females
how is MS an autoimmune disease
initiated by Th1 and Th17 which react against myelin Ag ( cellular immune response)
MS occurs more commenly where in the world
temperate latitudes
what happens in active plaque of MS
myelin breakdown
fewer oligodendrocytes
macrophages
lymphocytes, plasma cells
what happens in inactive plaque
little or no myelin
what are shadow plaques of MS
border between normal and affected white matter
-not sharply circumscribed
What are common signs and symptoms in MS from the brain stem
ataxia, nystagmus, internuclear opthalmoplegia
What are common signs and symptoms in MS from the spinal cord
motor and sensory impairment, spasticity, bladder dysfunction
what is a common sign and symptom for MS
unilateral vision impairment from optic nerve involvement
intranuclear ophthalmoplegia: pt looks left, left eye moves to left with nystagmus, right eye stationary
what are CSF values for MS
elevated protein
moderate lymphocytes and neutrophils
gamma Globulin increased
what is wrong in Neuromyelitis optica
Abs to aquaporin-4
areas of demylination show loss of aquaporin-4
what are clinical symptoms for Neuromyelitis optica
bilateral optic neuritis
prominant spinal cord involvment
what is another name for central pontine myelinolysis
osmotic demylinaton syndome
what causes central pontine myelinolysis
rapid correction of hyponatremia
acute hyponatermia causes cerebral edema
what is the pathogenesis of central pontine myelinolysis
adapt to loss of electrolytes
after correction brain shrinks
clinical symptoms of central pontine myelinollysis
dysarthria , lethargy
partially reversable
appear 2-6 days following rapid correction
what part of the braine does central pontine myelinolysis impact
symmetrical loss of myelin- diffuse or in brain stem, pontine tegmentum
what patients are at risk for central pontine myeliniolysis
alcoholics
liver transplant
electrolyte imbalance
BeriBeri is associated with what vitamin
Thiamine B1
B1 deficiency may cause ? if it goes untreated what can it cause
Wernicke Encephalopathy
Korsakoff ( memory disturbances)
what type of patients are at risk for beriberi
alcoholics
Gastric disorders
Thiamine deficiency effects what part of the brain
MAMMILLARY bodies
3 and 4 ventricles
in thiamine deficiency memory disturbances are caused by lesions in what areas
medial dorsal nucleus of thalamus
what are clinical features of B12 deficiency
ataxia
parasthesias of lower extremities
spastic weakness of paraplegia
what and which axons are impacted by B12 deficiency
degeneration of axons
- ascending tract
descending pyramidal tract
subacute combined degeneration of spinal cord
hypoglycemia resembles what
hypoxia
what areas are impacted by hypoglycemia
large pyramidal neurons of ctx
hippocampus
cerebellum
hyperglycemia is seen in what type of patients
uncontrolled diabets M.
hyperglycemia can cause what and precaution treatment is taken
dehyrdation
rehydration may cause cerebral edema, SLOW rehydration
hepatic encephalopathy have cellular response primarly in what? and what astrocytes are seen? what happens to neurons
glial
- alzheimer type II astrocytes seen in hyperammonemia
- no abnormalities of neurons
carbon monoxide poisening impacts what part of the brain
bilateral necrosis of globus pallidus
demyelination
how does methanol impact the brain
- degeneration of retinal ganglion cells
- selective bilateral putamenal necrosis
- focal white matter necrosis
clinical presentation for methanol
altered mental status
what is the pathology for ethanol
atrophy and loss of granule cells in anterior vermis
advance cases: loss of PUrkinje cells with astrocytes
pathology of radiation
coagulative necrosis effecting all elements of white matter.
