Patho Ch. 14 - Neurological Diseases

Pathophysiology Chapter 14-16 - Alterations in Cognitive Systems

“chronic, progressive failure of many cerebral functions including impairment of intellectual processes” defines:

dementia

_____ is not one specific disease but a group of diseases that causes cognitive decline such as loss of orientation, memory, language, judgement, decision making and altered behavior

dementia

dementia typically occurs in what age group

older people

dementia is NOT a normal _____, it is a sign of disease or brain damage

aging process

neuron degeneration, compression of brain tissue, atherosclerosis of cerebral vessels, brain trauma, genetic predisposition, CNS infections and neuroinflammation - these processes can all result in what condition

dementia

the most common etiology of dementia in the U.S. is _____ in nature

vascular

dementia vs alzheimers: dementia is a _____, alzheimers is a _____

symptom, disease

what is one example of a CNS infection that can cause dementia?

syphilis

what is an example of something that can cause dementia due to CNS damage that is non-infectious?

prolonged alcohol abuse

what is the microbe responsible for a syphilis infection

treponema pallidum

dementia in older individuals is typically _____-related, and dementia in younger individuals is typically _____-related

age, disease

the most common type of alzheimers disease is _____

age-related sporadic

“progressive neurological deterioration and continuing decline affecting memory, thinking skills, and the inability to carry out the simplest tasks” defines what condition:

alzheimers

what is the most common type of dementia in older people (condition?)

alzheimers

what is the key risk factor associated with alzheimers disease

increasing age

what are the forms of alzheimers disease?

early onset, late onset (non-hereditary)

late onset (non-hereditary) dementia typically accounts for what percentage of cases?

95%

late onset (non-hereditary) dementia typically occurs in what age range?

70-80+

what are the 2 causes/types of late onset (non-hereditary) dementia?

sporadic, altered apolipoprotein E (chromosome 19)

low levels of (or a defect/deficiency in) apolipoprotein E (chromosome 19) can cause _____, which in turn increases a persons risk for alzheimers

high cholesterol

people with untreated high cholesterol are at a greater risk of developing _____

alzheimers

early onset dementia typically accounts for which percentage of cases?

5%

early onset dementia typically occurs in what age range?

before 50

what are the two types of early onset dementia?

familial and non-familial

what causes familial early onset dementia?

autosomal dominant, chromosome 1 and 14

what is an example of a cause of non-familial early onset dementia?

extra chromosome 21 (down syndrome) causes buildup of amyloid plaque

alzheimers dementia or disease does not affect _____ function, it is more on the _____ side of symptoms

motor, cognitive

pathophysiology of alzheimers: what causes extracellular neuronal damage

deposition of beta-amyloid protein causing senile (aka neuritic) plaques

senile (aka neuritic) plaques are the result of _____, which causes extracellular neuronal damage leading to alzheimers

deposition of beta-amyloid proteins

what are the two pathophysiological pathways for alzheimers disease development?

extracellular and/or intracellular neuronal damage

pathophysiology of alzheimers: what causes intracellular neuronal damage

accumulation of tau protein causing neurofibrillary tangles

_____ are a hallmark of alzheimers disease, caused by accumulation of tau protein which results in disruption of the neuron's internal structure and interference with communication between neurons

neurofibrillary tangles

the _____ is the “tape” of the microtubule in a neuron, and dysfunction of this component causes neuron to rupture or die due to loss of structural integrity and loss of ability to transport signal/dispose of cellular waste

tau protein

accumulation of beta amyloid and/or tau proteins becomes _____ to neurons because it disrupts normal _____ by causing accumulation of toxins/waste - neuronal death causes dementia

toxic, cellular function

progression time frame of alzheimers disease:

10-20 years

an absolute/definitive diagnosis of alzheimers cannot be made in a living individual because the diagnosis requires a _____, which can only be done post-mortem. a diagnosis in a living individual will only be a high degree of certainty based on criteria, but not proven.

brain biopsy

drugs to treat alzheimers disease include:

anticholinesterase, aducanumab

“Progressive, neurodegenerative disease of the melanin-containing dopaminergic neurons in the substantia nigra, pars compacta (basal ganglia)” (due to buildup of alpha-synuclein protein - lewy bodies) defines what

parkinsons

abnormal clumps of alpha-synuclein protein that accumulate in nerve cells (neurons) in the brain. These deposits disrupt normal brain function and become toxic to cells

lewy bodies

pathogenesis of parkinsons: intraneuronal _____ (made of alpha-synuclein protein) cause toxicity to and kill the dopamine receptors of the _____. dopamine deficiency results in hypokinesia - this is because dopamine is excitatory.

lewy bodies, basal ganglia

pathogenesis of parkinsons: intraneuronal lewy bodies (made of alpha-synuclein protein) cause toxicity to and kill the _____ receptors of the basal ganglia. deficiency of this results in _____ - this is because this neurotransmitter is excitatory.

dopamine, hypokinesia

what are the two inhibitory neurotransmitter receptors

GABA and glycine

progression of parkinsons is typically a _____ onset

slow

what are the forms of parkinsons disease?

primary and secondary

what are the types of primary parkinsons disease?

idiopathic, genetic

what is the most common type of parkinsons disease?

primary idiopathic

what age does primary idiopathic parkinsons disease usually occur?

60+

what are the causes/types of secondary parkinsons disease?

environmental (pesticides), anti-psychotic medications, psuedo-parkinsonism

the _____ are 3 areas of the brain that are responsible for coordinating voluntary muscle movements, maintaining balance and posture, and ensuring smooth, accurate movements (Duong said this verbally in lecture, if its wrong… take it up with him)

cerebellum, basal ganglia, frontal lobe

a condition in which the patient has neuronal damage that causes similar signs and symptoms of parkinsons disease but does not meet the complete clinical criteria - they do not actually have the disease (think: muhammad ali, boxer)

pseudo-parkinsonism

stooped posture, masked facies, rigidity/stiffness, reduced arm swing when walking, resting tremor, jerky movements, slow movement, poor balance, the “pill roll” hand motion, and short shuffling steps are all clinical presentations of a person with what condition

parkinsons

the drug of choice for treating parkinsons disease is =

dopamine (levodopa)

parikinsons patients may experience a decrease in the ability to properly care for themselves, which may result in having more frequent _____

respiratory infections and UTIs

antivirals like amantadine decrease _____ in parkinsons patients

tremors

there is no specific _____ for parkinsons, diagnosis is based off of _____

testing, history and clinical presentation

“progressive, debilitating neurodegenerative disease that is inherited” defines:

huntingtons

huntingtons disease is also known as (second word means “artistic movement of the limbs”, happens later in the disease):

huntington chorea

huntingtons disease is inherited in what genetic pattern? does not skip a generation

autosomal dominant

a defect in _____ is responsible for huntingtons disease

chromosome 4

when does hungtingons disease typically manifest/start showing signs and symptoms?

early to late 40s

huntingtons disease affects _____ neurotransmitter receptors, so it is often known as a “_____” disease

inhibitory, hyperkinetic

pathophysiology of huntingtons disease: the huntington (HTT) gene codes for proteins involved in _____ (hint: 4 things). a defective gene creates defective proteins, which accumulate and cause neuronal death - this is what causes the disease.

signaling, transport, anti-apoptosis, and DNA repair

pathophysiology of huntingtons disease: huntingons affects the _____ and _____, causing depletion of gamma-aminobutyric acid (GABA) in the basal nuclei (caudate nucleus and putamen). levels of acetylcholine also appear to be reduced. this causes progressive atrophy of the brain.

basal ganglia (caudate nucleus), frontal cortex

pathophysiology of huntingtons disease: huntingtons affects the basal ganglia (caudate nucleus) and frontal cortex, causing depletion of _____ in the basal nuclei (caudate nucleus and putamen). levels of _____ also appear to be reduced. this causes progressive _____ of the brain.

gamma-aminobutyric acid (GABA), acetylcholine, atrophy

parkinsons vs huntingtons: which of the two involves dopamine deficiency - aka deficiency in excitatory neurotransmitter? (because it kills off neurons that produce excitatory neurotransmitters)

parkinsons

parkinsons vs huntingtons: which of the two involves gamma-aminobutyric acid (GABA) deficiency - aka deficiency in inhibitory neurotransmitter? (because it kills off neurons that produce inhibitory neurotransmitters)

huntingtons

reduced or diminished movement can be described as _____

hypokinetic

excessive, involuntary movement can be described as _____

hyperkinetic

mood swings and personality changes, restlessness, choreiform (purposeless) movements without conscious effort, emotional changes and dementia are all signs and symptoms of a person with what condition

huntingtons

huntingtons disease is diagnosed through _____

DNA analysis

most patients take a huntingtons disease diagnosis as a death sentence and may stop taking care of themselves. Because of this, it is important to monitor for _____ (hint: 3 things) in these individuals.

infections, heart disease, and suicide

“rapidly progressive and fatal neurodegenerative disease of the upper and lower motor neurons” defines:

amyotrophic lateral sclerosis (ALS)

amyotrophic lateral sclerosis (ALS) is aka:

Lou Gehrigs disease

amyotrophic lateral sclerosis (ALS) patients do not experience _____ decline, only _____ impairment

cognitive, physical

damage to upper motor neurons (aka 1st order neurons - brain to spinal cord) leads to impaired/no signal transmission to lower motor neurons, this results in _____

spastic paralysis

damage to lower motor neurons (aka 2nd order neurons - spinal cord to muscle) leads in impaired/no signal to the muscles, which results in _____

flaccid paralysis

amyotrophic lateral sclerosis (ALS) progression: as the disease worsens, patient becomes less _____ and more _____.

spastic, flaccid

in amyotrophic lateral sclerosis (ALS), there is no evidence of _____ around nerves as seen in other neurodegenerative diseases

inflammation

the most common cause of amyotrophic lateral sclerosis (ALS) is _____

mutation in SOD1 gene

accumulation of glutamate (waste) because astrocytes cannot uptake due to a mutation on SOD1 (superoxide dismutase 1) gene is associated with what disease

ALS

pathogenesis of amyotrophic lateral sclerosis (ALS): mutation in _____ gene causes damage to _____ uptake channels in _____, then excess of this waste causes toxicity to/death of neurons - causes the disease

SOD1, glutamate, astrocytes

besides the most common cause (mutation on SOD1 gene), what are the other causes of amyotrophic lateral sclerosis (ALS)?

gulf war veteran (toxic fume inhalation), and repeated head trauma (or TBI)

what is the primary cause of death in patients with amyotrophic lateral sclerosis (ALS)?

respiratory failure

the prognosis for amyotrophic lateral sclerosis (ALS) is _____ after diagnosis

3-5 years

riluzole (rilutek) - antiglutamate, edavarone - free radical scavenger, stem cells, and maintaining quality of life are all treatments for which condition

ALS

onset of multiple sclerosis is typically in what age range?

20-50 years

(canvas quiz) Parkinson disease is associated with:

a deficiency of dopamine in the substantia nigra

patients diagnosed with multiple sclerosis often have pathologic changes involving the:

oligodendrocytes

what effect do demyelinating disorders such as multiple sclerosis have on neurotransmission?

slow rate of action potential conduction

Steroids may be used in the management of acute exacerbation of symptoms in patients with multiple sclerosis, because:

demyelination is mediated by immune mechanisms

Which defective protein is associated with Parkinson’s disease?

alpha-synuclein

Upper extremity weakness in association with degeneration of CNS neurons is characteristic of:

ALS

what must happen before making a diagnosis of Alzheimer disease

rule out other potential causes of dementia

What systemic vascular disease is strongly associated with hemorrhagic stroke?

hypertension

“frequently occurring neurological disorders cause by pathologic processes in the blood vessels” describes:

cerebrovascular disease

pathogenesis of cerebrovascular diseases: 2 most common pathways =

ischemia (CVA or TIA), hemorrhagic (ICP)

increased intracranial pressure (ICP) will cause local _____ and general symptoms (think: blood pooling in cranium)

ischemia

an abnormal tangle of blood vessels where arteries connect directly to veins, bypassing the capillaries. blood mixes, O2 rich blood becomes O2 deficient blood & vice versa - can cause cerebrovascular diseases b/c end organ is not receiving the blood its supposed to

arteriovenous (AV) malformation

what are the types of cerebrovascular diseases?

TIA and CVA

what are the types of cerebrovascular accident (CVA) - stroke?

ischemic (thrombotic or embolic) and hemorrhagic