Midterm 2 Flashcards
(146 cards)
1
Q
What is the most common inherited cause of intellectual disability?
A
Fragile X syndrome - an X-linked genetic disorder
2
Q
What are the 2 types of FXS?
A
Full mutation FXS
Pre mutation FXS
3
Q
What causes FXS?
A
Caused by mutations to the Fragile X Mental Retardation (FMR) gene
This causes decreased levels of FMR protein (FMRP)
Normally people have 6-50 CGG repeats. however CGG repeats between 50-200 is considered FXS permutation FXS and over 200 is full FXS
4
Q
Why are X chromosomes unique?
A
You would assume that a female who has two X chromosomes would have double the amount of proteins and mRNA that are on the X chromosome
But in females the body works to silence one of the X chromosomes so both men and women have one functional X chromosome
5
Q
Is FXS more common in males or females? Why?
A
Males because they only have 1 X chromosome so they must express it
Whereas women have 2 so they have a backup copy and tend to exhibit milder symptoms
6
Q
If a father has a mutated X-linked chromosome which children will become affected?
What about when the mother has the mutated x chromosome?
A
Only the daughters because they get 1 X from their father and 1 X from their mother (genes will decide whether to exhibit the mutated or unmutated X). The sons cannot get it because they only get the Y chromosome from their father
Both sons and daughters get their X chromosomes from their mother it just depends which one they express. So both could be affected but they could also express the unmutated X chromosome
7
Q
If you have permutation FXS can you have children?
A
When have children you CGG repeats may expand causing more repeats and therefore your children may develop full mutation FXS
8
Q
What is the role of DNA methylation in FXS?
A
It turns off gene expression off
Elongation of CGG repeats allows hypermethlation of FMR1 gene at CpG islands - When this gene is silenced FMRP is not produced which has a major impact on the severity of FXS phenotype
9
Q
Where is the highest concentration of the FMR protein? What is the function in the body?
A
In the brain and testes - It appears to be critical for cognitive functioning and reproductive function
It functions to bind mRNA and transports it out of the cell nucleus to the synapse - suppressing mRNA
The lack of FMRP reduced mRNA suppression with impairs neuroplasticity
10
Q
How does FXS clinically present differently in men and women?
A
Males with the full mutation are severely impacted; the degree depends on the amount of CGG repeats
Degree of impairment varies in women depending on the ratio of normal:mutated FMR gene
Women with permutation do not show the phenotype
11
Q
What are some physical features of FXS?
A
- long, narrow face with prominent forehead and chin
- large ears
- testicular enlargement with normal function
- macrocephaly
- hypotonia
12
Q
What causes macrocephaly in people with FXS?
A
Increased caudate nucleus, fourth ventricles and hippocampal volume
This causes a decrease in lateral ventricle
The more abnormal the size of the caudate nucleus and lateral ventricle the more severe IQ impairment
13
Q
What are the cognitive symptoms of FXS?
A
Developmental delays
Intellectual disability
Learning disability
Boys typically have delayed language development and expression - poor articulation, repetitive
14
Q
FXS has different symptoms at different ages.
True or False
A
True
The symptoms reflect impairment in age-approbate brain development
Ex. in infancy poor such and in childhood impulsivity or aggression
15
Q
Is FXS difficult to diagnose?
A
YEs because in absence of family history the diagnosis is based on cognitive, developmental, and/or behavioural concerns
The earlier caught the better so appropriate interventions can be initiated - a simple genetic test for FMR1 gene can confirm suspicion of FXS
16
Q
What interventions can help FXS patients?
A
education plans, language therapy, behavioural therapy, pharmacotherapy to treat inattention, hyperactivity, anxiety, etc.
17
Q
What is down syndrome?
A
A genetic disorder caused by 3 copies of chromosome 21, also known as trisomy 21
18
Q
What is the most common chromosomal abnormality cause of intellectual disability?
A
Down syndrome
DS accounts for 1/3 of all intellectual disabilities worldwide
19
Q
Fetuses with trisomy 21 are more likely to be born stillbirth
True or False
A
True
Most fetuses with trisomy 21 do not make it through pregnancy
20
Q
What are the physical characteristics of DS?
A
It is regarded as a spectrum disorder as there is a variability of impairments
- small chin
- slanted eye
- hypotonia
- flat nasal bridge
- single crease of palm
- protruding tongue
- slowed growth in height
- flat & wide face, short neck, joint flexibility, extra space between big toe and second toe
21
Q
What health conditions are common amongst people with DS?
A
They have poor immune function and generally hit developmental milestones much later in age
They have increased risk of:
- heart defect
- epilepsy (5-10% in children and up to 50% in adults)
- leukaemia
- thyroid disease
- mental illness (30%)
- autism (5-10%)
- depression/anxiety - dementia/alzheimer
22
Q
What are the cognitive characteristics of people with DS?
A
- IQ ranges 35-69 but can be lower than 35 (normal is 100)
- Speech abnormalities : stutter, rapid or irregular speech, language comprehension is much more advanced than ability to speak
23
Q
How is DS diagnosed?
A
Often made by prenatal screening confirmed with a genetic test:
- chorionic virus sampling (CVS): cells are taken from the placenta in the 1st trimester
- Amniocentesis: sample is taken of the amniotic fluid surrounding fetus through a needle into the mothers uterus during the 2nd trimester
- DS can also be recognized from phenotypic features after birth
24
Q
What effect does maternal age have on DS?
A
Having birth later in life between 34-44 increase risk of DS
25
What occurs genetically when an individual has DS?
The extra chromosome happens by change and causes an over expression of each of the 300-500 genes carried on chromosome 21
It produces more mRNA which are translated into protein and whatever that protein does happens at a higher rate which throws off homeostasis
Your body doesn't silence the 3rd chromosome as in the X chromosome in the females
26
What is mosaic down syndrome?
Some of the cells in the body are normal while others have trisomy 21
Rare but results in a mild or undetectable form of DS
27
What causes trisomy 21?
Failure of the 21st chromosome during egg or sperm development - producing an extra copy
88% of cases result from the mothers egg and 8% in the fathers sperm and 3% after the egg and sperm have merged
28
Which genes are over expressed during DS?
It is not entirely clear but research suggests:
Beta amyloid - this overproduction occurs also in Alzheimer's disease
Superoxide dismutase (SOD)
29
What is beta amyloid
A protein derived from the amyloid precursor protein (APP) located on chromosome 21 which function is poorly understood
Possibly involved in activation of kinase enzymes, protection against oxidative stress, and regulation of cholesterol and iron transportation
It is the main component of amyloid plaques which are aggregates of misfolded proteins that are able to stick together and clog up the brain - the main cause of Alzheimer's
30
What is Superoxide dismutase (SOD) ?
The gene for SOD is located on chromosome 21
Oxidative stress is the imbalance between production and removal of oxygen-derived free radicals which causes decreased immune function, premature aging, and impaired mental function
SOD produces hydrogen peroxide which are less toxic than -02 but in the presence of ferrous iron it forms the highly toxic hydroxyl radical (OH) which has profound cellular damage
31
What is the treatment for DS?
There is no cure or treatment
However education and proper care can drastically improve QoL
Supplementation with antioxidant nutrients to prevent cellular damage from oxidative stress is proposed as a potential therapy for DS
32
What is a concussion?
Concussions are a mild traumatic brain injury
It is a biomechanical induced transient (temporary) disturbance of neurological function (it is due to movement) that may be associated with:
- loss of consciousness
- temporary loss of brain function
- a variety of physical, cognitive and emotional symptoms
33
What causes a concussion?
Rapid acceleration or deceleration of the brain resulting in the brain colliding with the skull
- coupe (first impact of brain) and then contrecoup (second impact of brain on opposite side)
Bruising and swelling follows can can persist for up to 48 hours and can cause cerebral edema increasing intracranial pressure
34
Which direction of impact causes the most severe concussion? Why?
Rotational - may cause bridging veins/synuses or corpus callosum to be sheared
Can cause diffuse axonal injury (DAI): shearing force cause axons to detach from cell body which causes release of the excitatory NT of glutamate that cause excitotoxic lesions 24-48 hours post injury
Midbrain and diencephalon are most affected by rotational forces which disrupt normal cellular function thought to produce LOC
Axon shearing often leads to a subdural hematoma -> a collection of clotted blood that increase pressure on the brain
This shearing may cause cellular death
35
What is an epidural hematoma?
Collection of blood between the dura mater and the skill rather than under as in subdural
36
_________ are viewed as the hallmark of brain damage following a brain injury
Brain contusions
37
What is the aftermath of a concussion?
A concussion can lead to neuronal and vascular tissue damage leading to a distortion of cell membranes
- neuronal activity picks up Glutamate
- cerebral blood flow is interrupted due to hematoma
The indiscriminate release of Glutamate produces the events known as the metabolic facade leading the a cerebral energy crisis
38
Which NTs increase during the neurmetabolic cascade following a concussion/
- glutamate
- glucose
- and a longer increased release of potassium and calcium
39
What is glutamate?
The main excitatory Nt in the brain that is present in more synapses than any other NT
It can bind to 3 post-synaptic receptors:
- AMPA
- NMDA
- Kainate
Thse also care Na+ into the postsynaptic cell and cause depolarization and EPSP
40
What is glutamate excitoxicty?
Exictotoxicity can occur with overexposure of glutamate (or other excitatory NT) caused by a prolonged depolarization of the post synaptic neurons
When subjected to prolonged stimulation a large % of cells die by either:
- Necrosis: rapid lysis of cells due to osmotic swelling (more severe death)
- Apoptosis: delayed cascade of biochemical events that leads to DNA breakup and ultimately cell death
Glutamate activating NMDA receptors can allow entry of Ca2+ (a second messenger) into the cell that at high concentrations are extremely toxic
- interrupts function of mitochondria and ATP production is hindered and can initiate apoptosis
41
How does exitotoxicity lead to an energy crisis?
Glutamate increases entry of Ca2+ which hinders ATP production
ATP is required for entry and fueling Na-K pumps; Na-K are working in overdrive which requires a ton of ATP which results in an increase in glucose metabolism
This glucose demand comes at a time when verbal blood flow is reduced and mitochondria are dysfunctional
Hypoglycemia ensues, leading to cognitive deficits and an energy crisis that leads to secondary injuries
42
What are secondary injuries caused by concussions?
BBB permeability: anaerobic glucose metabolism (glycolysis) produces lactate followed by lactic acid - this overproduction results in acidosis which damages the BBB, leaving it vulnerable to toxins
Inflammation: microglia activation results in cellular damage leading to apoptosis
These secondary injures can take days, weeks, months, or months to develop and can persist for years
43
What are the symptoms of concussion?
Symptoms vary but can include:
- headache, pressure in the head -> vascular indies
- LOC -> brain stem
- Confusion -> corpus collosum
- amnesia surrounding event -> hippocampus, frontal lobes
- Ringing in ears -> temporal lobes
- Nausea/vomiting -> area postrema (good sign something is seriously wrong)
- changes in mood and emotional disturbances -> amygdala
44
How are concussions detected and diagnosed?
- Sport concussion assessment tool (SCAT-5)
- checklist of signs/symptoms of trauma, memory test, neurological screen
- Concussion Recommendation Tool or Immediate Post Concussion & Cognitive Testing (ImPACT)
- Computer tests aimed at detecting post-concussive symptoms, 20 min neurocognitive test
45
What is second impact syndrome (SIS?
SIS occurs when an individual suffers a concussion while still symptomatic from a pervious concussion
SIS carries a 50% mortality rate, 100% mobility rate (something wrong)
Repeated concussions have a cumulative effect on the human brain
46
What is chronic traumatic encephalopathy (CTE)?
CTE (aka demential pugilistic) is the result of multiple, sub-concussive blows to the head
CTE is a progressive degenerative disease found in individuals with repeated head trauma - characterized by neurofibrillary tangles, beta amyloid , amyloid plaques and neural death
This causes dementia and are all found in people with Alzheimer
47
The brain consumes ____% of the body's blood supply
15-20
48
What are the two major arteries that supply blood to the brain?
The internal carotid arteries: branches into the anterior cerebral, and middle cerebral arteries
Vertebral arteries: branches into the posterior central artery
The species regions the arteries supply blood to can aide in diagnosing a stroke
ex. the posterior supplies the occipital lobe
49
The _____ is targherting during choke/sleeper holds
carotid artery
50
The middle cerebral artery stoke is most likely to affect the _____
Broca's area - loss in speech
51
What is the Circle of Willis? What is its function?
A collection of arteries at the base of brain
The communicating arteries link the right and left sides of the circle allowing for anatomical redundancy
This means that if one artery is blocked, blood may be able to bypass it and still supply much of the brain
52
What is a stoke?
An abnormality of the vascular supply causes damage to the CNS
The blockage must occur long enough and cause damage that impairs the body beyond 24 hours+ to be considered a stroke
53
What are the two main types of strokes?
Ischemic (lack of blood flow)
Hemorrhagic (caused by bleeding)
54
What are the common symptoms of a stroke?
Symptoms usually occurs unilaterally
Common symptoms are:
- weakness in face and/or limbs
- numbness (loss of sensation)
- Aphasia or dysarthria
- vision loss
- headache (common in hemorrhagic stroke only)
Rare symptoms:
- LOC
- Pain
- Abnormal movement
Remember FAST: Facial droop, Arm weakness, Speech difficulty = Time to call 911
55
What is an ischemic stroke and what are the main causes?
An ischemic stroke is caused by a blockage of arterial blood vessels
The two main causes are:
- Thrombosis: obstruction of a blood vessel by local blood clot
- Embolism: obstruction due to an embolus from elsewhere in the body
56
What happens to brain tissue when it is deprived of oxygen?
Brain tissue ceases to function if deprived for more than 60-90sec and will suffer irreversible damage after ~3 hours of schema
The body is not very good at generating ATP in absence of oxygen (lactate -> lactic acid -> acidosis) leading the an energy crisis that causes apoptosis or necrosis (very similar to what occurs during concussions)
Infarction is the tissue death (necrosis) caused by lack of blood supply
57
What is a hemorrhagic stroke and what the the main types?
Hemorrhagic stoke refers to bleeding in our about the brain membrane usually caused by a rupture of blood vessel or abnormal vascular structure (aneurism)
4 main types are:
- *Epidural: between skull and dura matter
- *Subdural: between the dura matter and arachnoid space
- Sub-arachnoid: between arachnoid space and pia matter
- Intracerebral: bleeding within the brain itself. Either from the brain tissue (intraparenchymal hemorrhage) or from the brains ventricular system (intraventricular hemorrhage)
58
What are symptoms that are specific to hemorrhagic strokes?
- severe headache
- dizziness
- seizures
- vomiting
59
What occurs after infarction?
After necrosis there is a release of osmotically active (causes pressure gradient) substances (ex. arachidonic or lactic acid) which causes a cerebral edema (fluid build up)
Axon swelling cause unravelling of myelin sheath, inflammation forms glial scars around infarct and neovascularization occurs ~2 weeks
By 3-4 days interstitial fluid accumulates in around the infarct which is the most dangerous period
Cell death is caused by cereal edema and herniations (shifting of position)
Recovery of function can be achieved by restoration of perfusion (pressure) which settles the edema
60
Which risk factors are associated with stroke?
The biggest risk factor is hypertension accounting for 35-50% of risk
Other factors include:
- tobacco
- high blood cholesterol
- diabetes mellitus (1 % 2)
- lipids
- atrial fibrillation
- obesity
- age >75
61
If you have hypertension how can you prevent strokes?
- blood pressure medication
- anticoagulation drugs
- surgery (remove atherosclerosis)
- Proper nutrition
62
How is a stroke diagnosed?
Diagnosis is based on a physical exam supported by CT and MRI imaging
A perfusion CT scan is an imaging technique that allows up to visualize blood flow
CT angiography and cerebral anagrams use dye to visualize blood vessels and locate clots that can be removed
63
What is stoke rehabilitation?
The attempt to recover lost function that include physical, occupational and speech-language pathologists
IT is often possible to regain function by neuroplasticity since brain damage cannot be reversed (this decreases with age)
64
What is Parkinson's disease?
A long-term degenerative disorder of the CNS
Symptoms generally come on slowy over time and mainly affect the motor system
65
The average life expectancy following PD diagnosis is between _____ years
7-14
However people are often diagnosed after years of having it
66
Who most commonly gets PD?
Men over 60 yrs
Anyone under 60 who gets PD is considered young-onset
It occurs in ~1 in every 500 people
67
What are the motor symptoms of PD?
TRAP
- tremor at rest
- Rigidity
- Akinesia
- Postural instability
68
What is parkinsonism?
All of the symptoms of PD are collectively known as parkinsonism - PD is the most common cause of parkinsonism but it is not the only one (ex. antipsychotic drugs)
69
What is parkinsonism gait?
People with PD tend to walk with flat feed and as the disease advances they begin to take smaller shuffling steps
Festination is the tendency of people with PD to stoop forward
70
What are the characteristics of tremor at rest?
- Asymmetrical: don't occur the same on each side
- slow velocity
- 'pill-rolling' - twisting their fingers around
- most commonly affect chin, jaw, arms, legs
Most common presenting symptom
71
What are the characteristics of rigidity?
Occurs in 90% of patients
Characterized by increased resistance
- cogwheel phenomenon is when they move in jerky ways
Increased muscle tone and contraction
Occurs most commonly in the neck, shoulders, hips, wrists, ankles
72
What are the characteristics of bradykinesia?
The most characteristic clinical feature: present in every single case of PD
- Slowness in performing activities of daily life
- Loss of spontaneous movements & gesturing
- Monotonic & typhonic dysarthria (speech)
- Loss of facial expression (hypmimia) and decreased blinking
- Drooling
- Reducing arm swinging while walking
73
What are the characteristics of postural instability?
- Loss of postural reflexes
- manifestation of late stage PD
- Can lead to impaired balance
- Most common cause of falls
74
What are the non-motor symptoms of PD?
- Psychiatric disturbances
- Autonomic disturbances (constipation, sexual dysfunction, orthostatic hypertension)
- Cognitive impairment
- Sleep disturbances (insomnia, narcolepsy, REM behaviour disorder)
75
What is the structure of the basal ganglia?
It is composed of the:
Dorsal stratum: caudate nucleus and putamen
Globus Pallidus: externa Gpe, Interna Gpi
Substantia Nigra: Pars compacta, pars reticula
Subthalamic nucleus
76
What can the basal ganglia do?
The basal ganglia sets the overall 'tone' or 'motivation' for action
Once a voluntary action has been decided, the BG helps overcome inhibition in the motor circuits and ensures the smooth execution of that action
BG output dictates the likelihood that movements will occurs
It is organized into loops with specific functions
77
What are the 4 loops in the basal ganglia?
1. Cognitive loop: turns on/off regions in the frontal lobe, task switching, priority setting
2. Visual/Oculomotor Loop: scanning environments, spatial recognition
3. Affective loop: emotional (desire, apathy, impulse)
4. Motor loop: to move or not to move (putamen, globs pallidus and substantia nigra)
78
What happens neurologically to individuals with PD?
There is death of neurons in the region of the midbrain called the substantial nigra
These neurons produce DA and axons from this area project to the caudate nucleus and other parts of the striatum/basal ganglia
Thus there is a decrease in DA production
79
What is DA's role in PD?
DA neurons in the substantia nigra form strong connections with other regions of the basal ganglia and the motor cortex.
They are excitatory connections - the dorsal striatum (motor) has dense expression D1 and D2 DA receptors
The loss of DA due to cell death impact the stimulation of the nervous system and lead to no voluntary movements
80
DA is the only NT involved in PD
True or False
False - it is just the best studied
- Noradrenergic - urinary frequency, erectile dysfunction
- Serotonergic - Sleep disturbances
- Cholinergic: constipation
81
Substantia Nigra is the only brain region affected by PD
True or False
False - PD is progressive
Degeneration begins in the olfactory bulb and dorsal motor nucleus in brain stem
Then the the locus coerulus in brain stem
Then the substantia nigra
Finally the cortex
82
What causes cell death in PD?
PD is mostly idiopathic so we don't know
Genetics: typically early onset is associated with genetics, 15% have a 1st degree relative, 5-10% occur due to a mutation
Environmental: toxins/pollutants, head injuries, infections (syphilis), side effects of drugs (MPTP), injury (stroke/lesions)
83
What are Lewy Bodies?
Lewy bodies formation is associated with PD
They are abnormal aggregates of the alpha-synuclein protein that leads to spherical masses in the cytoplasm and displace other cell components
They lead to apoptosis of affected neurons
These cause the cell death in the substantia nigra
84
What are the treatments for PD?
Levodopa (L-DOPA)
- precursor to DA that results in temporal improvement in motor symptoms (get more out of the cells you have)
- Long-term use can lead to dyskinesias, hallucinations, agitation
- Fluctuations with good and poor responses
COMT Inhibtors & MAO-B inhibitors
- Block enzymes that degrade DA
- Can be used to compliment L-DOPA in early stages
- Modest relief when used alone
DA agonists
- bind to DA receptors and reduce motor symptoms of PD
- less effective than L-DOPA
Non-pharmacological treatment
- eduction, support, exercise, nutrition
85
What surgical options are available for PD?
Deep Brain Stimulation (DBS)
- electrodes are implanted in a target region deep in the brain and stimulated with a low-voltage current to receive some PD motor-symptoms
Stem Cell Treatment
- Healthy DA cells can be plugged into the SN
86
What is Huntington's Disease?
HD is a genetic, hereditary, progressive neurodegenerative disorder caused by a dominant mutation in the Huntington gene on chromosome 4
87
If one of your parents have HD what are the chances you will get Huntington's?
If your affected parent gives you the affected gene you will 100% develop HD since it is dominant
However, your affected parent has a 50% chance of giving you the unaffected gene
88
Males are more likely to inherit HD
True or False
False - males and females are equivalent it is due to the presence of an affected chromosome
89
What is the common age of HD onset?
Between the ages of 35 and 55
Most likely have already had kids
90
What are the symptoms of HD?
Symptoms do not appear until later adulthood and are progressive (start subtly and progress to more pronounced)
Symptoms include:
- Abnormal movements (involuntary movements, dystonia, motor coordination) known as chorea
- cognitive difficulties
- emotional difficulties
Eventuallythe motor and intellectual deterioration becomes so severe people are completed incapacitated with loss of memory
91
What are the progression of symptoms in HD?
Early stages: face trunk and limbs move involuntary and rapidly, but not too noticeable
Middle: muscles begin to contract briefly and rapidly, arms and other body parts suddenly jerk, uncoordinated movements
Later: cognitive impairments, irritability, changes in interests, severe depression, death occurs 13-15 after onset
92
Striatum contains groups of specialized neurons called ______. What are the two types?
Medium spiny neurons (MSN)
MSN are specialized GABAergic cells (inhibitory) and represent ~95% of neurons in the striatum
MSN's can be separated on the bassi of which DA receptor they express:
- Direct (D1) MSN excite their output structures and promote associated behaviours
- Indirect (D2) MSN inhibit output structures and associated behaviours
93
Describe the normal circuits of the basal ganglia
Direct: The thalamus sends excitatory signals to the motor cortex unless the globus pallidus interna (GPi) is activated which sends inhibitory (GABA) signals to the thalamus. The GPi can be turned off by sending D1 MSN signals from the striatum which receive their input from the motor cortex . The D1 MSN are activated by DA from the substantia nigra
Indirect: The substantia nigra activates D2 MSN in the striatum which inhibits the globus pallidus externa (GPe) which typically inhibits the subthalamic nucleus which typically excites the GPi. When the GPe is invited it sends a stronger inhibitory signal to the subthalamuc nucleus which activated the GPi sending excitatory signals to the thalamus that sends signals to the motor cortex
94
How does HD impact the basal ganglia?
It causes damage to the neurons in the basal ganglia (D2 MSN) and consequently loss of its inhibitory output to the thalamus is thought to account for the movement disorders
The caudate putamen and globes pallidus are the most affected
95% loss of MSN are seen in later stages of the HD
Affected areas have intranuclear inclusion bodies and perinuclear aggregates of Huntingtin that cause interference of cellular function and activate apoptosis
95
What is the basal ganglia circuit in HD?
D2 MSN die and the GPe is no longer inhibited so it sends a very strong inhibitory signal to the subthalamic nucleus
This turns of the GPi and there is now nothin to inhibt the excitatory signal sent to the motor cortex from the thalamus
96
What is the basal ganglia circuit in PD?
The D2 start sending a stronger inhibitory signal to the subthalamic nucleus which sends a very strong excitatory signal to the GPi which then sends a very strong inhibitory signal to the thalamus which inhibits input to the motor cortex
97
What is the genetic mutated gene in HD?
The dominant gene is huntingtin (HTT) which produces the Huntingtin protein
HTT contains an expanded CAG repeating coding for polyglutamine in huntingtin protein
CAG repeat lengths between 10-25 are mortal bu HD patients have CAG repeated above 36 - the longer the repeat length the earlier onset
98
Where are huntingtin proteins expressed? How are they impacted in HD?
Mostly in the brain
HD patents have misfiled huntingtin proteins that aggregate together, particularly in the dorsal striatum D2 MSNs
mutated HTT genes are thought to activate caps proteins and initiate intrinsic apoptotic pathways that are involved in preprogrammed cell death (death occurs in a controlled manner)
99
How is HD detected and diagnosed?
We can perform genetic testing that reveals if a person carries the mutated HTT gene
Diagnosis is typically based on symptoms, family history, imaging and genetic testing
Stress can speed up the onset
100
What is the treatment for HD?
There is not cure but treatment can reduce severity
Caregiving becomes extremely important
Exercise can help rehabilitate cognitive sympttoms
101
What is tetrabenazine?
A pharmacological treatment for chorea
It is thought to deplete monoamines from nerve terminals that inhibts vesicular monoamine transport 2 resulting in decreased NT reuptake
102
An individual is cycling when a Canadian goose recklessly cuts them off. They brake to narrowly avoid the goose, fall- and impact the caudal part of their head. Where would the contrecoup force be applied within the brain?
A) Parietal Lobe
B) Occipital Lobe
C) Temporal Lobe
D) Pre-Frontal Cortex
D) Pre-Frontal Cortex
103
An individual was involved in a car accident and experienced a violent concussion. Before completely healing, they experience another very gentle concussion. The symptoms were worse the second time, why?
A) Gentle concussions are always worse than violent concussions if they impact the frontal lobe.
B) The individual is likely suffering from second impact syndrome.
C) Their pain pathways were desensitized from the original concussion which would lead to worsened symptoms such as migraine.
D) The individual was intoxicated during the second concussion, and they're likely just hungover.
B) The individual is likely suffering from second impact syndrome.
104
Which diseases are characterized by the presence of trinucleotide expansions?
A) Parkinson's Disease and Huntington's Disease
B) Down Syndrome and Dementia
C) Huntington's Disease and Fragile X Syndrome
D) Fragile X Syndrome and Down Syndrome
C) Huntington's Disease and Fragile X Syndrome
105
__________ producing neurons have axons in the ____________ that project to the caudate nucleus and other parts of the striatum/basal ganglia. These neurons help ensure the smooth execution of motor functions.
A) Dopamine, substania nigra
B) 5-HT, substantia nigra
C) Dopamine, globus pallidus
D) 5-HT, globus pallidus
A) Dopamine, substania nigra
106
Which of the following statements regarding the huntingtin (HTT) protein is false?
A) Neurodegeneration caused by misfolded HTT proteins occurs in the cerebral cortex first
B) HTT proteins are expressed in non-neuronal cells
C) The normal functioning of the Htt protein is dictated by the number of CAG repeats in the HTT gene
D) Misfolded and aggregated HTT proteins induce apoptosis through the activation of caspases
A) Neurodegeneration caused by misfolded HTT proteins occurs in the cerebral cortex first
107
According to the article 'The X-Factor in Fertility and Neurological Health', damage to the white matter in the _ _ _ is highly specific to individuals with FXTAS.
A) Cerebellum
B) Middle cerebellar peduncles
C) Frontal lobes
D) Corpus callosum
B) Middle cerebellar peduncles
108
Huntington's Disease is characterized by the loss of _______________ neurons in the striatum that results in the activation of the _____________, while Parkinson's Disease is characterized by the loss of ___________________ neurons in the substantia nigra that results in the activation of the ______________.
A) MSN; subthalamic nucleus; dopaminergic; globus pallidus externa
B) GABAergic; thalamus; dopaminergic; globus pallidus interna
C) GABAergic; globus pallidus interna; dopaminergic; subthalamic nucleus
D) Dopaminergic; subthalamic nucleus; GABAergic; motor cortex
B) GABAergic; thalamus; dopaminergic; globus pallidus interna
109
What type of inheritance pattern is displayed in Huntington's Disease?
A) Sex-Linked Recessive
B) Sex-Linked Dominant
C) Autosomal Dominant
D) Autosomal Recessive
C) Autosomal Dominant
110
The highest risk of concussion is found within which demographic
A) Young men
B) Old women
C) Old men
D) Young women
A) Young men
111
According to the article, The Huntington's Paradox, which of the following statements regarding the huntingtin (HTT) gene is false?
A) The HTT gene first acquired CAG repeats in echinoderms
B) During the later stages of prenatal development, the HTT gene is critical for the formation of new neurons and the connections between them
C) The earliest form of the gene contained no CAG repeats
D) The length of the CAG repeats only varies in humans and mice
D) The length of the CAG repeats only varies in humans and mice
112
Which of the following is most likely to have the highest degree of impairment of FXS?
A) Males with 250 CGG repeats
B) Females with 54 CGG repeats mother, 175 CGG repeats father
C) Males with 204 CGG repeats mother, 274 CGG repeats father
D) Females with 250 CGG repeats, low activation ratio
A) Males with 250 CGG repeats
113
Which of the following does NOT affect the age of onset in Huntington's Disease?
A) Length of CAG expansion
B) All options affect age of onset
C) Maternal immune activation during pregnancy
D) Psychological stress
C) Maternal immune activation during pregnancy
114
In pathological brain injury, excitotoxicity disrupts the equilibrium of neuronal signalling by:
A) Glutamate leaking out of ruptured cells interacting with NMDA receptors
B) GABA leaking out of ruptured cells and interacting with NMDA receptors
C) Glutamate leaking out of ruptured cells interacting with OXT receptors
D) GABA leaking out of ruptured cells interacting with AMPA receptors
A) Glutamate leaking out of ruptured cells interacting with NMDA receptors
115
According to Article #4 "A New Way to Help Manage Parkinson's" within two year of starting levodopa therapy ….
A) Patients will not experience OFF episodes after starting levodopa therapy
B) Roughly a third of patients experience OFF episodes
C) Roughly a quarter of patients expereince OFF episodes
D) Roughly half of patients experience OFF episodes
D) Roughly half of patients experience OFF episodes
116
Which of the following could be useful as a diagnostic marker of concussion?
A) IL-1
B) Glutamate
C) s100B
D) APP
C) s100B
117
One of the earliest neuronal indicators of a traumatic brain injury is
A) Massive influx of Na+
B) Massive influx of K+
C) Massive efflux of K+
D) Massive efflux of Na+
C) Massive efflux of K+
118
What is primary axotomy?
A) A surgical procedure used to treat Parkinson's
B) The technical name for a lobotomy
C) An injury that occurs when an axon is torn apart
D) The motor pathway leading from the primary motor cortex to the spinal cord
C) An injury that occurs when an axon is torn apart
119
An individual presents with hypotonia, mild to moderate intellectual disability, poor immune function, and has increased beta amyloid production. When presented with a karyotype test, the karyotype had 46 chromosomes. This individual would be diagnosed with having _ _ _.
A) Mosaic Down Syndrome
B) Fragile X syndrome
C) Down syndrome
D) Alzheimerís disease
A) Mosaic Down Syndrome
120
According to the article, The Huntington's Paradox, which of the following is not a function of the huntingtin (HTT) gene in amoeba?
A) Inhibits cell migration
B) Regulates the response to environmental stimuli that are associated with food
C) Regulates asexual reproduction
D) Promotes aggregation of cells
A) Inhibits cell migration
121
Which of the following structures is NOT found within the Basal Ganglia
A) Dorsal Striatum
B) Putamen
C) Globus Pallidus
D) Thalamus
D) Thalamus
122
Each turn of the sodium-potassium ATPase results in the influx of ___, the efflux of ___, and the consumption of one molecule of ATP.
Incorrect Response
A) 3Na+, 2K+
B) 3K+, 2Na+
C) 2Na+, 3K+
D) 2K+, 3Na+
D) 2K+, 3Na+
123
Parkinson's Disease and Huntington's Disease both arise due to neuronal loss in the ________________. This pathology results in __________________ in Parkinson's Disease and _________________ in Huntington's Disease.
A) Substantia Nigra; akinesia; dystonia
B) Striatum; Chorea; bradykinesia
C) Caudate; bradykinesia; chorea
D) Basal Ganglia; hypokinesia; hyperkinesia
D) Basal Ganglia; hypokinesia; hyperkinesia
124
According to Dr. MacKay, using salt to draw water out of an eggplant before cooking it is an example of
A) Neuroinflammatory response
B) How to reduce lactic acid
C) Cerebral Edema
D) Osmosis
D) Osmosis
125
In class Dr. MacKay uses _________________ as an analogy for the communicating arteries in the Circle of Willis.
A) Bypass lanes on the highway
B) Being stuck in really bad traffic repeatedly
C) Using a roundabout
D) Making an ileagal left hand turn
A) Bypass lanes on the highway
126
Which of the following correlates with the degree of impairment seen in males with Fragile X syndrome?
A) All options listed
B) Decreased expression of FMR1 gene
C) Decreased levels of FMRP
D) Size of the amplification of CGG sites
A) All options listed
127
In Article #4 " A New Way to Help Manage Parkinson's" the author highlights
A) How after a diagnosis of PD, symptoms tend to NOT be well controlled by levodopa for the first couple years
B) How OFF episodes are periods when a PD patient can resume normal functioning
C) How having an array of novel treatments for PD paves the way for an increase in precison medicine
D) How an array of novel treatments have cured PD
C) How having an array of novel treatments for PD paves the way for an increase in precison medicine
128
A 25-year-old woman, whose father had Huntington's Disease, is undergoing genetic testing to determine if she will go on to develop the disease. How many copies of the mutant HTT allele does she need in order to develop Huntington's Disease?
A) 1 copy
B) 36 copies
C) 10 copies
D) 25 copies
A) 1 copy
129
The neuropathology of Huntington's Disease affects the _____________ pathway of the basal ganglia, whereas the neuropathology of Parkinson's Disease affects the ________________ pathway of the basal ganglia.
A) Indirect; indirect and direct
B) Indirect; direct
C) Direct; indirect
D) Direct and indirect; direct
A) Indirect; indirect and direct
130
A subdural hemorrhagic stroke occurs …
A) In the brains ventricular system
B) Between the dura matter and the arachnoid space
C) Between the arachnoid space and the pia matter
D) Between the skull and the dura matter
B) Between the dura matter and the arachnoid space
131
According to Dr. MacKay, the decreased lateral ventricle volume seen in Fragile X syndrome is most likely related to:
A) All of the options listed
B) Increased third ventricle
C) Increased hippocampal volume
D) Increased caudate nucleus
D) Increased caudate nucleus
132
An epidural hematoma can be classified as;
A) The pooling of blood within the ventricles
B) The pooling of blood within the pia mater and the skull
C) The pooling of blood within the spinal column
D) The pooling of blood between the dura mater and the skull
D) The pooling of blood between the dura mater and the skull
133
Lewy bodies are made of up which of the following substance?
A) Tau
B) Alpha-synuclein
C) Beta-amyloid
D) Tumor necrosis factor alpha
B) Alpha-synuclein
134
The basal ganglia helps to coordinate voluntary movement by ___ of the primary motor cortex.
A) activating inhibition
B) inhibiting excitation
C) Inhibiting inhibition
D) activating excitation
C) Inhibiting inhibition
135
Which basal ganglia pathology best explains the symptoms of Huntington's Disease?
A) D2 MSN death in the striatum results in the inhibition of the globus pallidus externa which leads to the activation of the motor cortex
B) D2 MSN death in the striatum results in the activation of the globus pallidus interna which leads to the inhibition of the motor cortex
C) D2 MSN death in the striatum results in the activation of the globus pallidus externa which leads to the inhibition of movement
D) D2 MSN death in the striatum results in the inhibition of the globus pallidus interna which leads to the activation of the motor cortex
D) D2 MSN death in the striatum results in the inhibition of the globus pallidus interna which leads to the activation of the motor cortex
136
Robert Sapolsky theorizes that the mutant HTT allele continues to persist in the general population because:
A) Increased psychological stress is leading to an increase in the number of CAG repeats with each successive generation
B) One of the earliest symptoms of Huntington's Disease is reduced inhibition and this can lead to risky sexual behaviour that results in children before a clinical diagnosis is made
C) Individuals are having more children on average than they were 50 years ago resulting in a higher probability of children with the mutant HTT gene
D) Individuals are deciding to have children later in life
B) One of the earliest symptoms of Huntington's Disease is reduced inhibition and this can lead to risky sexual behaviour that results in children before a clinical diagnosis is made
137
Which of the following does NOT contribute to the oxidative stress seen in Down syndrome?
A) Superoxide dismutase
B) Ferrous iron
C) Hydroxyl radical
D) Zinc
D) Zinc
138
According to the article 'The X-Factor in Fertility and Neurological Health', which of the following statements regarding female permutation carriers is FALSE?
A) One in five female permutation carriers will develop primary ovarian insufficiency
B) Mothers with midsize repeats produced more cortisol than those with more CGG repeats
C) All mothers of fragile X children are themselves premutation carriers
D) Female premutation carriers are not affected by the buildup of RNA and protein
D) Female premutation carriers are not affected by the buildup of RNA and protein
139
Which statement regarding Trisomy 21 and Down syndrome is FALSE?
A) Advanced paternal age is the most significant risk factor associated with Down syndrome
B) A majority of cases of trisomy 21 result from nonseparation of the chromosomes in the mother
C) Trisomy 21 results in increased expression of genes for beta amyloid and SOD
D) Trisomy 21 is a result of the failure of the 21st chromosome separating during egg or sperm development
A) Advanced paternal age is the most significant risk factor associated with Down syndrome
140
What are motor proteins?
A) Dietary nutrients that support smooth function of the muscles/joints
B) Specialized structures that agitate fluid within the synaptic cleft, ensuring proper distribution of neurotransmitters
C) Enzymes which help transport neurotransmitters and other products to the synaptic terminal
D) Proteins in dopaminergic neurons that form aggregates in Parkinson's disease
C) Enzymes which help transport neurotransmitters and other products to the synaptic terminal
141
In terms of traumatic brain injury, which is worse?
A) Necrosis, because it initiates an inflammatory response
B) Apoptosis, because it initiates an inflammatory response
C) Apoptosis, because it results in cellular fragmentation
D) Necrosis, because it results in cellular condensation
A) Necrosis, because it initiates an inflammatory response
142
According to the article, The Huntington's Paradox, research into the huntingtin (HTT) gene and CAG repeats found that:
A) The length of the CAG repeats is positively correlated with the complexity of an organism's nervous system
B) Individuals who have a lower number of CAG repeats have more grey matter in their globus pallidus
C) CAG repeats are associated with cognitive decline
D) The amino acid that CAG codes for inhibits protein synthesis
A) The length of the CAG repeats is positively correlated with the complexity of an organism's nervous system
143
Results from Zaccato and Cattaneo's experiments outlined in The Huntington's Paradox, showed that:
A) Mouse embryonic stem cells that were missing the healthy HTT gene developed abnormally shaped neural rosettes
B) The amphioxus HTT gene produced larger neural rosettes in mouse embryonic stem cells than the fish HTT gene
C) The older the evolutionary history of the organism, the larger the neural rosette
D) The HTT gene inhibits the cleavage of adhesion proteins by enzymes, allowing neural rosettes to adhere to each other
D) The HTT gene inhibits the cleavage of adhesion proteins by enzymes, allowing neural rosettes to adhere to each other
144
The circle of Willis is
A) A small area located in the cerebellum
B) A collection of arteries at the base of the brain
C) A collection of capillaries on the brain stem
D) A collection of veins at the base of the brain
B) A collection of arteries at the base of the brain
145
The reduced blood flow in the secondary phase of a traumatic brain injury causes;
A) A switch to aerobic metabolism
B) Alkalosis
C) A switch to glucose metabolism
D) Increased lactic acid production
D) Increased lactic acid production
146
A patient who displays chorea and dystonia is admitted to the hospital to undergo surgery. The neurosurgeon plans to implant an electrode that can be activated to deliver direct stimulation to the brain with the goal of reducing the patient's symptoms. In which part of the basal ganglia should the neurosurgeon implant the electrode?
A) Globus Pallidus Externa
B) Subthalamic Nucleus
C) Substantia Nigra Pars Reticulata
D) Thalamus
B) Subthalamic Nucleus
