Translational Physiology Block 2

Question 1

What is a dysraphism?

Answer 1

Incomplete closure of the neural tube

Question 2

When do the anterior and posterior pores in the neural tube close in humans?

Answer 2

Closure of the neural tube in humans normally occurs between 26 and 28 days of gestation.

Question 3

What is the most serious dyraphism? Describe it.

Answer 3

anancephaly: the cerebral hemispheres are absent and the rest of the brain is severely malformed. Overlying malformations of the skull, brain coverings, and scalp are present (effects both ectoderm (skin, nervous tissue) and mesoderm (skull))

Question 4

Which dyraphism of the posterior pore does not result in a pathological condition? Approximately where in the spinal cord is this malformation?

Answer 4

Spina bifibida occulta; fifth lumbar or first sacral vertebra

Question 5

What is it term used for when the dura and arachnoid membranes herniate (i.e., protrude) through the vertebral defect? if the spinal cord also herniates?

Answer 5

spina bifida cystica; myelomeningocele

Question 6

What is it term used for when the dura and arachnoid membranes herniate (i.e., protrude) through the cranial defect? if the brain also herniates?

Answer 6

meningocele; cephalocele

Question 7

What protein is elevated in dyraphisms?

Answer 7

alpha fetoprotein

Question 8

What are the known causes of dyraphisms?

Answer 8

folic acid deficiency, maternal heat exposure, and polygenic mutations

Question 9

Describe the steps in axonal degeneration.

Answer 9

Step 1: Synaptic transmission occurring at the axon terminal fails within hours because this complex process is dependent on material provided by axonal transport; Step 2: entire distal segment of axon is destroyed and removed (Wallerian); Step 3: myelin degenerates (Schwann cell may secrete trophic factors that help in recovery); Step 4: macrophages and Schwann cells in the PNS scavenge the debris created by the breakdown of the axon and its myelin; Step 5: After axonal injury, most neuron cell bodies swell and undergo a characteristic rearrangement of organelles called chromatolysis. The nucleus also swells and moves to an eccentric position. The endoplasmic reticulum, normally close to the nucleus, reassembles around the periphery of the cell body. Chromatolysis is reversible if the neuron survives and is able to re-establish its distal process and contact the appropriate target.

Question 10

What is retrograde degeneration? anterograde?

Answer 10

the neuron that synapses on the injured cell undergoes degeneration; neuron that received synaptic contacts from an injured cell degenerates

Question 11

What are general symptoms of neuropathies?

Answer 11

numbness (sensory), weakness (motor), parathesias (tingling or pain)

Question 12

How do neuropathies usually present in patients?

Answer 12

Neuropathies are first presented in the feet (longest axon) and spread upwards and later more proximally

Question 13

What are two signs of motor neuron injury (LMN) and muscle atrophy?

Answer 13

Fasciculations: muscle cells may twitch in unison. These small twitches can be seen under the skin (result of spontaneous action potential in injured motor neurons); Fibrillations: individual muscle fibers may twitch spontaneously (in the absence of motor neuron (LMN); suggestion that Schwann cells may release acetlycholine)

Question 14

Understand different types of hydrocephalus, and the location of blockage which would affect the size of the ventricle(s) and drainage

Answer 14

Communicating hydrocephalus occurs when the flow of CSF is blocked after it exits the ventricles. This form is called communicating because the CSF can still flow between the ventricles, which remain open (problem absorbing CSF into SSS through arachnoid granulations); Damage to the arachnoid villi can occur most commonly from infection or inflammation of the meninges or from the presence of an irritating substance, such as blood in the CSF after a subarachnoid hemorrhage (normal pressure hydrocephalus: LP reveals normal ICPs; enlargement of all four ventricles on MRI, characterized by progressive dementia, urinary incontinence, and gait disturbance); Non-communicating hydrocephalus — also called “obstructive” hydrocephalus — occurs when the flow of CSF is blocked along one or more of the narrow passages connecting the ventricles. One of the most common causes of hydrocephalus is “aqueductal stenosis.” In this case, hydrocephalus results from a narrowing of the aqueduct of Sylvius, a small passage between the third and fourth ventricles in the middle of the brain; Hydrocephalus ex-vacuo occurs when stroke or traumatic injury cause damage to the brain. In these cases, brain tissue may actually shrink.

Question 15

How is hydrocephalus treated?

Answer 15

shunting

Question 16

Describe a lumbar puncture.

Answer 16

A hollow needle for sampling of CSF can be safely inserted into the subarachnoid space at the level of the L3-L4 interspace (cord ends at L1). With the patient lying on the side, normal (opening) pressure varies from 100 to 180 mm H 2 O (in this position lumbar CSF pressure corresponds to intracranial pressure); Queckenstedt test: gently compressing the external jugular veins in the neck for 10 seconds (rapidly increases intracranial pressure because it increases the volume of intracranial venous blood. It quickly leads to an increase in lumbar pressure)

Question 17

What can cause increased CSF pressure? What procedure should a physician not do in this case?

Answer 17

CSF pressure can become elevated because of a pathological mass within the cranium, such as a tumor or collection of blood, or because the brain is swollen as a result of injury or infection; i. Attempting a lumbar puncture in these patients is risky, since a small loss of CSF or CSF leak following lumbar puncture can cause brain herniation (pressure gradient that results from low lumbar CSF pressure)

Question 18

Describe cerebral edema.

Answer 18

increase in BECF where extra fluid comes from intravascular compartment; If the cerebral edema is generalized, it can be tolerated until intracerebral pressure exceeds arterial blood pressure, at which point blood flow to the brain stops; Symptoms: headache, vomiting, altered consciousness; Body responds by raising blood pressure, hyperventilating (alkolosis and vasoconstriction); treatment: mannitol (increases blood osmolarity)

Question 19

What can cause increased extracellular glutamate? Why is this a pathologic condition?

Answer 19

ischemia, anoxia, hypoglycemia, or trauma; The action of rising levels of extracellular glutamate causes increased uptake of sodium into neurons causing swelling; excitotoxicty also damages astrocytes (swelling resulting from potassium uptake and water)

Question 20

What is vasogenic edema? What causes it?

Answer 20

Vasogenic edema occurs when there is a leak in the BBB allowing protein to cross drawing water osmotically to increase the volume of BECF and ICF

Question 21

Know types of glial cells and role of myelin in the CNS

Answer 21

oligodendrocytes, astrocytes, and microglia; myelin speeds up conduction by insulation (saltatory)

Question 22

Immunopathogenesis of multiple sclerosis

Answer 22

Cell-mediated immunity: CD4 helper 5 cells release cytokines causing tissue damage; Humoral immunity: B lymphocytes secrete autoantibodies and serve as antigen presenting cells; Immunoregulatory cells: decreased activity of regulator cells

Question 23

Basic pathology of multiple sclerosis

Answer 23

active plaques, multiple areas of demyelination + gliosis + inflammation + initial relative axonal preservation; lymphocyte infiltration: more CD8 cytotoxic T lymphocytes and fewer CD4, beta, and plasma cells

Question 24

Is remylelination a feature of early MS?

Answer 24

Yes

Question 25

Does nerve degeneration and axonal loss happen early in MS? Why is primary stage of the disease have milder symptomology to later stages?

Answer 25

Yes; Resolving inflammation, remyelination of axons, and the relative plasticity of the CNS initially compensate for axonal injury (once these fail (much like Diabetes) disease and disability from it become progressive)

Question 26

What are the major causes of axonal and neuronal loss from MS?

Answer 26

Cortical and meningeal inflammation, Wallerian degeneration, and either ischemia or edema

Question 27

Know basics of clinical and MRI diagnosis of MS

Answer 27

Dissemination in time, space, or both (more than one T2 lesion, new lesion at follow-up); sites of lesions: periventricular, corpus callosum, cerebellum, juxtacortical (GM-WM junction)); other features: black holes (atrophy), flame-shaped, perpendicular to ventricles and parallel to longitudinal axons, larger than 0.5 cm

Question 28

How does a physician treat multiple sclerosis?

Answer 28

prednisone (steroid, anti-inflammatory) is used to MS relapses (does not prevent new attacks); Immunomodulators: BG-12, laquinimod, teriflunomide; Reduction in immune cell proliferation: Alemtuzumab; T cell adhesion and transmigration prevention: Natalizumab; future directions: stem cell therapy and remyelination

Question 29

What are symptoms associated with multiple sclerosis?

Answer 29

sensory and motor deficits, visual loss, ataxia (loss of balance), diplopia, vertigo

Question 30

Why is gadolinium an important diagnostic tool for MS?

Answer 30

Gadolinium enhancement of a MS lesion on MRI represents BBB damage, which enables infiltration of inflammatory cells into the CNS

Question 31

How does the length constant change in patients with MS?

Answer 31

Decrease in length constant via a decrease in membrane resistance (axoplasmic resistance unchanged)

Question 32

A patient complains of blurry vision in their left eye and is diagnosed with optic neurtis? Where is the nerve damage?

Answer 32

Left optic nerve (inflammation); may also cause diplopia (symptoms can be related to MS)

Question 33

What explains the remission/relapse component of MS?

Answer 33

inflammation attacks (resolution of these attacks)

Question 34

How can MS, a demyelinating disease, result in gray matter injury?

Answer 34

Axonal injury leading to chromatolysis

Question 35

Why do MS patients feel relief from their disease burden at cooler temperatures?

Answer 35

Action potential duration is slower at colder temperatures

Question 36

Would K+ voltage gated channel blockers called aminopyridines be useful in treatment of an MS patient?

Answer 36

Yes, because repolarization would be slowed

Question 37

What would be the expected result on an EMG of an MS patient?

Answer 37

Normal peripheral conduction velocity

Question 38

In another inflammatory demyelinating disease, Guillain-Barre Syndrome, the peripheral nervous system is attacked. Would the patients muscle tone and reflexes remain intact?

Answer 38

No; muscle flaccidity and hyporeflexia

Question 39

What would be the expected findings in the CSF of a MS patient? How are remyelinated axons of different from the from the damaged axons?

Answer 39

elevated IgG levels; Nav1.2 channels may replace Nav1.6 channels in demyelinated axons. Conduction is often barely adequate under normal circumstances and may become inadequate under stressful situations, such as illness, emotional stress, and exhaustion.

Question 40

What are risk factors for stroke?

Answer 40

hypertension (other cardiac history), smoking, prior stroke, diabetes, blood-borne diseases (sickle-cell), obesity, alcohol (non-modifiabled: age, race, gender, genetics)

Question 41

Describe major blood flow in the brain.

Answer 41

Anterior circulation: supplies cerebral hemispheres (fed by carotid arteries); posterior circulation: supplies brainstem & occipital lobe (fed by basal artery (anastomose of vertebral arteries)); most arteries are interconnected (anterior and posterior; left and right) by an intact Circle of Willis

Question 42

What are the different type of stroke?

Answer 42

Hemorrhagic (20%)- 60% ICH, 40% SAH; ischemia (80%)- 20% cardiac embolism, 20% large vessel, 25% lacunar (small vessel) (blood flow is blocked)

Question 43

What are common causes of ischemic stroke?

Answer 43

arteriosclerosis plaques, atrial fibrillation, other heart failure

Question 44

What are common cause of hemorrhagic stoke?

Answer 44

hypertension, AVMs, anticoagulants (warfarin) (arteriolar lipohyalinosis results from chronic HTN; more likely to rupture); SAH are caused by ruptured aneurysms

Question 45

What are the most common signs of stroke?

Answer 45

Sudden, Painless, Focal neurological dysfunction; Sudden, severe, uncharacteristic headache (sometimes LOC)

Question 46

T/F: Depressed consciousness and headaches are a sign of infarcts or ischemic events?

Answer 46

False; hemorrhagic

Question 47

Mean arterial pressures above the point of cerebral blood flow autoregulation result in what two pathophysiologies?

Answer 47

edema and hemorrhage (below a certain point, ischemia occurs); hypertensive patients have a curve shifting to the right

Question 48

Who are ideal candidates for iv t-PA treatment? What is t-PA treatment?

Answer 48

Tissue plasminogen activator (breaksdown clots); no hemorrhage apparent and no history of chronic hypertension (may result in reperfusion hemorrhage) with the patient arriving at the hospital within a 4.5 hour time window following ischemic onset

Question 49

Looking at a patient’s chart, you note that he has had a previous occlusion in the most proximal segment of his anterior cerebral artery, which of the following symptoms would you expect he had at the time?

Answer 49

Nothing; Collateral blood flow from the contralateral anterior cerebral artery through the communicating artery

Question 50

Describe the pathophysiology of axonic brain injury

Answer 50

Cessation of cerebral circulation results in depletion of oxygen stores within 20 sec; Cessation of synaptic activity and action potentials (LOC); Within 5 min, brain glucose and ATP stores are depleted (loss of NaK pump; cell depolarization, later causes neurotoxicity); oxidative free radicals, lactic acidosis, and prostaglandins/thrombaxane A2

Question 51

What is the pathophysiology of reperfusion injury?

Answer 51

hyperfusion followed by hypoperfusion; Formation of oxygen free radicals, cytokines, apoptosis; poor blood flow due to viscosity of blood and perivascular edema; inability of pericytes to regulate vessel size (no-reflow phenomenon)

Question 52

Which parts of the brain are selectively vulnerable to hypoxia/ischemia?

Answer 52

most important: thalamus, reticular formation, periaqueductal gray area; CA1 & CA4 regions of hippocampus (memory), amygdala, cerebellar vermis, and caudate nucleus

Question 53

Describe the role of the thalamus and cortex in coma recovery and ways to explore this connectivity

Answer 53

reperfusion injury is followed by dysregulated or aberrant thalomcortical activity (needed to respond to external stimuli; arousal); these could be tested by inducing and recording somatosensory evoked potentials in the ventroposterior lateral nucleus of the thalamus and somatosensory cortex (stimulate a sensory nerve)

Question 54

What are predictors of poor prognosis for patients post cardiac arrest? How do these predictive markers change in patients undergoing hypothermia treatment?

Answer 54

myoclonic status epilepticus, absence of bilateral N20 somatosensory evoked potentials, high expression of neuron-specific enolase in blood (poor predictor), absence of pupillary and corneal reflexes as well as extensor posturing or no movement to noxious stimuli 3 days after the cardiac event; patient must have at least predictors of poor outcome (suggested to conduct a neural exam following 4-5 days)

Question 55

What is Cushing's triad?

Answer 55

increase to increased intracranial pressure; heart rate decreases to increase MAP; respiratory dysfunction (shallow breathing)

Question 56

What is the Monroe-Kellie doctrine?

Answer 56

The Monro-Kellie hypothesis states that the cranial compartment is incompressible, and the volume inside the cranium is a fixed volume. The cranium and its constituents (blood, CSF, and brain tissue) create a state of volume equilibrium, such that any increase in volume of one of the cranial constituents must be compensated by a decrease in volume of another (The easiest thing to displace, that which requires the least amount of force, is venous blood followed by CSF and then arterial blood)

Question 57

Describe the intracranial pressure waveform.

Answer 57

P1 (percussion wave): arterial pulsation; P2 (tidal wave): (normally a smaller peak) intracranial compliance; P3 (dicrotic notch): aortic valve closure; if P2 is higher than P1 - it indicates intracranial hypertension.

Question 58

ICPs should be kept below which point?

Answer 58

20 mm Hg

Question 59

What are Lundberg waves?

Answer 59

predictor of poor prognosis; three waveforms (A waves are pathological. There is a rapid rise in ICP up to 50-100 mm Hg followed by a variable period during which the ICP remains elevated followed by a rapid fall to the baseline and when they persist for longer periods)

Question 60

How does breathing effect the autoregulation of cerebral blood flow?

Answer 60

breathing decrease CO2 (increases blood pressure); this results in cerebral vasoconstriction (decreased blood flow)

Question 61

What can cause increased intracranial pressure?

Answer 61

intracranial etiologies: ICH, tumor, pseudotumor, infection, trauma, and hydrocephalus

Question 62

What is the equation for cerebral perfusion pressure? What are normal values for CPP?

Answer 62

CPP = MAP (1/3 systolic + 2/3 diastolic pressure) - ICP; 50-150 mm Hg

Question 63

Which brain region receives the highest normal cerebral blood flow? Does white matter or gray matter receive greater normal blood flow?

Answer 63

neurohypophysis; gray matter

Question 64

A mean arterial pressure of 125 mm Hg or above causes what pathophysiology? below 50 mm Hg?

Answer 64

in both situations, cerebral autoregulation is not intact; for high MAPs, edema will ensue (vessels remain dilated); for low MAPs, ischemia (vessels remain constrict)

Question 65

How does hypertension effect the autoregulation of blood flow?

Answer 65

The of MAPs on the x axis and CBF on y axis is shifted to the right

Question 66

What happens to vessel size with increasing MAPs in situations of autoregulatory failure?

Answer 66

Vasodilation and increase in both cerebral blood flow and intracranial pressure

Question 67

How does a neurointensivist treat a patient with intracranial pressure above 25 mm Hg?

Answer 67

Targets: cerebral perfusion pressure of 60-70, ICPs below 20; position patient with head up 30-45 degree angle, ventilation (mild hyperventilation), mannitol (osmotherapy), sedatives (barbituates), hypothermia, and decompressive craniectomy

Question 68

Why is hypothermia effective treatment for brain injury?

Answer 68

minimizes apoptosis, reduction of oxidative free radicals, decrease disruption of BBB, prevents excitotoxicity

Question 69

Describe the basic pathology and symptoms of Parkinson's disease.

Answer 69

characterized by motor symptoms: rigidity, bradykinesia (slowness in execution of movement), tremor (occur at rest and disappear during activity), and postural instability (shuffling gait); pathologic progression: olfactory system (loss of smell) followed by autonomic system (loss of GI function), limbic system, sensorimotor system; loss of dopaminergic neurons from substantia nigra pars compacta

Question 70

Describe the general features of the basal ganglia and thalamocortical networks

Answer 70

When you take away the dopamine, activity in the direct pathway (striatal cells to GPi to thalamus) goes down, and motor activity goes down (dopamine excites striatal cells); dopamine normally inhibits the indirect pathway (striatal cells to GPe to subthalamic nucleus to GPi to thalamus); acetylcholine has opposite effect to dopamine

Question 71

Describe the basic biophysics of electrical stimulation in the brain. Are there alternatives?

Answer 71

DBS pulses: 100 Hz, 2-5 V with the hope that they form bidirectional action potentials in the neighboring neurons (surgical target: subthalamic nucleus; complications: avoiding overstimulation or stimulation of the internal capsule nearby; alternative therapy: pallidotomy

Question 72

Define dementia. What are the types of dementia?

Answer 72

acquired loss of cognitive abilities occurring in clear consciousness; Alzheimer's disease, prion disease, chronic traumatic encephalopathy

Question 73

Is dementia acute or progressive?

Answer 73

progressive; intermediate state: mild cognitive impairment

Question 74

How is dementia diagnosed?

Answer 74

One of more of aphasia, agnosia (loss of recognition), apraxia (inability to do skilled movements), executive functions (not related to a single event like urinary tract infection); MRI evidence of black spots (neuronal atrophy); impairment in contrast-sensitivity

Question 75

How is Alzheimer's diagnosed?

Answer 75

PET scanning; beta amyloid plaques (derived from APP cleavage Chr. 21, may present 15 years prior to disease onset, low AB in the blood, first targets association cortex of parietal lobe and prefrontal cortex, extracellular); tau protein neurofibrillary tangle (intracellular component of actin-microtubule complex, prion-like spreading cell to cell, evident in CTE, familial mutations have been discovered, first targets entorhinal cortex of temporal lobe); APOE4: impairment of microglia to clear out beta amyloid plaques

Question 76

What are treatments for Alzheimer's disease?

Answer 76

Acetylcholinesterase inhibitors (loss of acetylcholinergic neurons from basal forebrain results in dementia? seems to be necessary for memory function); NMDA receptor inhibitors (neurotoxicity (too much extracellular glutamate leading to neuronal cell death; sustained activation of NMDA receptors) are suggested causes of Alzheimer’s disease symptoms; Mematine is proposed to return NMDA receptors to normal physiologic ranges where magnesium is capable of blocking ion entry; too much inhibition is not beneficial such as usage of PCP and ketamine)

Question 77

T/F: Some Alzheimer's patients lack beta amyloid plaques?

Answer 77

True

Question 78

Besides multiple sclerosis, what are other known demyelinating diseases?

Answer 78

progressive multifocal leukoencephalopathy: occurs in patients with AIDs, infection of oligodendrocytes with polyomavirus (fatal); central pontine myelinolysis: demyelination following rapid correction of hyponatremia with salt infusion or rapid correction of hypernatremia; Guillan-Barre: patients may recover because it effects the peripheral nerves, which can re-generate

Question 79

What is the importance of the PHOX2B gene?

Answer 79

A transcription factor required for development of visceral control systems (not in preganglionic sympathetic neurons)

Question 80

What is congenital central hypoventilation syndrome (CCHS)? Hirschprung disease? Name of the syndrome for the combined pathophysiologies?

Answer 80

heterozygous mutation in PHOX2B gene characterized by breathing problems during sleep (Deficiency in detection of oxygen and carbon dioxide by chemoreceptors or dysfunction of NTS); enteric nervous system does not develop properly in colon; Haddad syndrome

Question 81

How does a vagus nerve stimulator help epilepsy patients?

Answer 81

vagal afferent input (influences many rostral brain structures); May reduce number of seizures by half (stimulates the nerve daily or can be mechanically stimulated prior to an aura)

Question 82

Describe Horner's syndrome

Answer 82

Combination of unilateral ptosis, miosis (small pupil), and anhidrosis (lack of sweating); syndrome of the sympathetic neurons innervate the smooth muscle that elevates the eyelid, the pupillary dilator, and the sweat glands of the face; First-order Horner syndrome: affects the hypothalamus or the axons traveling down from the brain to the ipsilateral intermediolateral column (other brainstem abnormalities can be co-expressed); Second-order Horner syndrome: disruption of axonal signal from lateral intermediolateral column to the paravertebral column; Third-order Horner syndrome may result from a complication during a carotid artery dissection (damage to the wall of the artery) (affects postganglionic neuron)

Question 83

What are the tests to diagnose Horner's syndrome?

Answer 83

Test 1: administration of cocaine (block NE uptake); in a healthy person, this would cause pupil dilation (not in a patient with Horner’s); Test 2: administration of hydroxyamphetamine (Paredrine) (releases NE from synaptic terminals) (no pupil dilation in a patient with Horner’s)

Question 84

Describe the various color-blind diseases.

Answer 84

result of mutation in visual pigment genes (opsins); i. L or M pigment mutations: X-linked recessive (less common mutation is S pigment on Chr. 7); A single abnormal pigment can lead to either dichromacy (the absence of one functional pigment) or anomalous trichromacy (the absorption spectrum of one pigment shifted relative to normal), often with a consequent inability to distinguish certain colors.

Question 85

What can damage the cochlea?

Answer 85

genetic factors, a variety of drugs (e.g., some antibiotics, including quinine), chronic exposure to excessively loud sounds

Question 86

How can a cochlear implant improve hearing? Who are the best candidates for the device?

Answer 86

electric cochlea (nerve must be intact): cochlear implant exploits the tonotopic arrangement of auditory nerve fibers; Young children and older children or adults whose deafness was acquired after they learned some speech.

Question 87

What is the difference between paresis and paralysis?

Answer 87

paresis: weakness; paralysis: loss of motor function

Question 88

Are reflexes present in patients with lower motor neuron injury?

Answer 88

No

Question 89

What happens when a nerve (innervating a muscle) is transected?

Answer 89

muscles become flaccid (atonia) and eventually develop profound atrophy (loss of muscle mass) because of the absence of trophic influences from the nerves.

Question 90

T/F: Complete transection of the spinal cord leads to profound paralysis above the lesion?

Answer 90

False

Question 91

Complete transection of the spinal cord affecting the both legs is called? both legs, trunk, and arms? only one side is affected? Describe the consequences of such a transection

Answer 91

paraplegia; quadraplegia; hemiplegia; For a few days after an acute injury, there is also areflexia and reduced muscle tone (hypotonia), a condition called spinal shock. The muscles are limp and cannot be controlled by the brain or by the remaining circuits of the spinal cord (days to months); following spinal shock, patient presents with exaggerated muscle tone ( hypertonia ) and heightened stretch reflexes ( hyperreflexia ) with related signs—this combination is called spasticity (loss of brain modulation)

Question 92

Where are the different sources for neural stem cells in the developing and in the adult brain?

Answer 92

developing: SVZ, external germinal layer (cerebellum); adult: SVZ, subgranular zone (hippocampus)

Question 93

What are characteristics of stem cells?

Answer 93

multipotent, ability to self-renew, anti-apoptotic, surrounded by a niche

Question 94

Describe some of the basic methodologies (cultured cells vs. transgenic animal models) used in investigating cancer stem cells.

Answer 94

Transgenic: hyperplasia of EGL in non-neoplastic cells can form tumors, loss of Hedgehog pathway proteins can be a precursor to cancer, p53 and NF1 in GBM; cultured: many groups have shown that culturing patient-derived tumors in neural stem cell conditions form tumors in vivo; potential markers (refuted): CD133, side population (ABC transporter)

Question 95

Define cancer stem cells and describe studies in support and against their role/importance in cancer.

Answer 95

"stem-like" tumor cells (also known as tumor-initiating cells); combined activation of KRas and AKT only forms tumors in CSC cells (not in differentiated populations), aberrant EGFR signaling (down-regulated Ink4a/Arf) can transform cells with either CSC phenotype or differentiated phenotype; resistant to radiation/chemotherapy;

Question 96

Describe the concepts of “dedifferentiation” and “cell of origin”

Answer 96

ability of differentiated cells to acquire the ability to self-renew; exogenous EGF can dedifferentiate non-neoplastic differentiated cells of the brain; cell of origin describes the cell thought to have acquired for the first mutation or mutational program in the development of cancer

Question 97

What embryonal signaling pathways have been shown to play a role in cancer?

Answer 97

EGFR, Notch, Hedgehog (patched & Gli; inhibited by Smo), Wnt

Question 98

What are the two competing models regarding tumor heterogeneity?

Answer 98

stochastic: Cancer cells of many different phenotypes have the potential to proliferate extensively, but any one cell would have a low probability of exhibiting this potential in an assay of clonogenicity or tumorigenicity; cancer stem cell: a subset of cancer cells consistently proliferate extensively in clonogenic assays and can form new tumours on transplantation

Question 99

Describe the four steps (in order) that help clinicians reach the final or pathological diagnosis in a patient with neurologic symptoms, and which one of these steps is the most important.

Answer 99

phenomenology (signs and symptoms; most important), physiologic disturbance, anatomical diagnosis, pathological diagnosis

Question 100

List the main rubrics of the neurological examination.

Answer 100

arousal and orientation, cranial nerves, neurovascular, motor, sensory, stance & gait, reflexes, ANS

Question 101

List the various categories of disease processes that may affect the nervous system

Answer 101

trauma, infection, immune/inflammatory, neoplasm, vascular, metabolic, and degenerative

Question 102

What is an acute focal lesion of the CNS? subacute? chronic?

Answer 102

stroke from either an infarct or hemorrhage; seizure; migraine; infection or inflammation; mass

Question 103

What is an acute diffuse lesion of the CNS? subacute? chronic?

Answer 103

cardiac event or seizure; meningitis or metabolic disorder; degenerative syndrome

Question 104

A stroke is a decrease in brain function due to what?

Answer 104

disturbance in arterial blood flow to the brain

Question 105

Do subarachnoid hemorrhages present with focal symptoms?

Answer 105

No

Question 106

T/F: If a patient presenting with a stroke does not experience loss of consciousness, the stroke is most likely a result of an infarct

Answer 106

True

Question 107

T/F: Cerebral blood flow only occurs if MAP is above ICP

Answer 107

True

Question 108

What causes a coma?

Answer 108

Most severe: bicortical dysfunction; less severe: damage to reticular activating system (thalamus and periaqueductal gray)

Question 109

A patient comes to the ER with headache and vomiting. MRI reveals generalizaed cerebral edema. Which of the following is likely true of the patient?

Answer 109

in this case, the patient has elevated intracranial pressure; if the patient's cerebral blood flow remains autoregulated, then the goal of the body is to raise cerebral perfusion pressure in opposition of the high ICPs; this can be done by raising the mean arterial pressure by hyperventilating (decreased CO2 increase blood pressure)

Question 110

Describe the Circle of Willis

Answer 110

Anterior-posterior: anterior cerebral artery (interconnected by ACOM) connects MCA through the ICA; basilar artery (anastomosis of vertebral arteries) gives rise to the posterior cerebral artery and connects to anterior circulation by PCOM