Neuro Week 2

Question 1

What is conjunctivae and what are the 3 parts ********

Answer 1

• Conjunctiva is the mucous membrane that covers the front of the eye and lines the inside of the eyelids.
• 3 parts are; 1) Palpebral conjunctiva 2) Bulbar conjunctiva 3) Fornix conjunctiva

Question 2

What is the limbus

• transition of what 2 parts
• which part is clear? Not Clear?

Answer 2

Limbus is the transition from the clear cornea to the opaque sclera

• •Both Clear cornea and opage sclera have collagen
• •Cornea collagen is parallel (why it is clear)
• •Sclera collagen is crisscross (why it is not clear)

Question 3

Where do tears come from and what’s the deal with all these sources

Answer 3

• •Lacrimal – aqueous layer (water)
• •Goblet cells – Mucin layer (glue)
• •Meibomian glands – Lipid layer (sealant)

***Lipid layer is top most area (Meibmian glands)

***Lacrimal glands (aqueous largest part)

Question 4

What is the cause of dry eyes? (2)

Answer 4

1) DECREASED PRODUCTION

• •A decrease in aqueous production by the lacrimal gland
• •Keratoconjunctivitis Sicca
• •infiltration of the lacrimal tissue by mononuclear cells is most common cause
• •Can treat with immune modulaters

2) INCREASED DEMAND

• •Evaporative loss
• •Poor lipid layer
• •“Why do you say my eyes are dry when tears stream down my cheeks?” keep producing more aqueous

Question 5

2 functions of ciliary bodymuscle function

Answer 5

• •Ciliary muscle changes the shape of the lens
• •Ciliary body is responsible for aqueous fluid production in the eye

•Important to under stand the difference between aqueous fluid in the eye and the aqueous layer of the tear film.

Question 6

What is choroid

• function
• 3 components that make the uveal tract

Answer 6

• •Choroid is the pigmented vascular layer of the eyeball between the retina and the sclera.
• •Choroid, ciliary body and iris makes the uveal tract.
• •Provide oxygen and nourishment for the outer layers of the retina

Question 7

Where is sensory retina derived from?

• what tumor is related to this?

Answer 7

• •The diencephalon is the region of the embryonic vertebrate neural tube that gives rise to anterior forebrain structures including the thalamus, hypothalamus, posterior portion of the pituitary gland, and pineal gland.
• •Tri-lateral retinoblastoma

Question 8

Fetal vaculature (inside the eye)

• COMPLETELY REABSORBED BY HOW MANY WEEKS OF GESTATION

Answer 8

• A vascular stalk extends from the optic nerve head to the posterior lens.
• Does anybody see what might be the problem with this?
• should be completely reabsorbed by 34 weeks gestation
• Incomplete reabsorption can lead to PFV/ PHPV
• Also important consideration with premature birth.

Question 9

THE LENS

• Function
• Properties

**Describe infoliation

Answer 9

The Lens

• •It bends light (refracts)
• •It converges light (Plus power)
• •Note that refractive power is measured in diopters.
• •Positive diopters converge light/ negative diopters diverge light

Special properties of the lens

• •It is the only part of the refractive poertion of the eye that can change its power (by changing its shape)
• •Why would it do that?
• •It is encapsulated (no contact with the outside world!/ No escape)
• •It is made of epithelial cells (nothing special about that)
• •Epithelial cells are constantly replaced, but the lens can’t exfoliate!
• •So infoliation occurs (that’s the special part)

INFOLIATION

• •This causes the lens to increase in size with age
• •Becomes less elastic – can’t change shape anymore (not so special now!), this leads to presbyopia.
• •Also changes color
  
  • •What color is the ideal lens? Clear
  • •Infoliation contributes to cataracts

Question 10

Case

A man says something is growing on his eye

• •A life guard in Ecuador, spends his time off at the beach.
• •This things been on his eye for a couple of years, getting bigger and more red.
• •Want to look at it?

Answer 10

PTERYGIUM

• •A triangular sheet of fibrovascular tissue which grows over the cornea (crosses the limbus)
• •Higher incidence the closer one is to the equator
• •Sun exposure, outdoor work is a risk factor
• •Ethnicity is probably not a risk factor.
• •Elastotic degeneration (sun exposure and other risk factors.)

Question 11

Uber driver of the pterygium patient also came in thinking she also has pterygium.

What does she have?

Answer 11

Pinguecula

• •A pinguecula is a deposit of protein, fat, or calcium.
• •Doesn’t cross the limbus
• •Both pinguecula and pterygium are believed to be caused by a combination of dry eyes and exposure to wind, dust, and ultraviolet (UV) light from the sun.

Question 12

A 45 year old fellow has a bump on his eyelid

• •It doesn’t hurt
• •Been there for six weeks
• •He had one a couple of years ago, but it went away on its own.
• •Want to see it?

Answer 12

CHALAZION

• •Inflammatory, not infection
• •Meibomian gland obstruction (remember meibomian gland secretes lipids in the eyelids)
• •Specifics: chronic lipogranulomatous inflammatory lesion caused by blockage of meibomian gland orifices and stagnation of secretions

Question 13

Same uber driver that picked up the patient with Chalazion

Answer 13

HORDEOLUM

• •Microabscess (infectious)
• •Usually staph
• •Glands of Zeis and Moll

Question 14

A lady brings in her brand new baby

• •She thinks he has an eye infection
• •Started when the baby was 6 days old
• •Any thoughts?

The Uber driver also has a new baby

• •Her baby has an eye infection that started 36 hours after birth!
• •Any thoughts?

***2 organisms?? TreatMent??

Answer 14

Neonatal Conjunctivitis / Ophthalmia Neonatorum

• •Most important to differentiate between Gonococcal and Chlamydia
• •Treat with oral antibiotics, not topical
• •It is good to know the timing, but definitive diagnosis is made by Gram stain, culture and sensitivity, etc

Gonococcal

• Gonococcal usually appears 24-48 hours (1-2 days) after birth (UBER DRIVER BABY).
• •Treated with systemic Penicillin (or equivalent)

Chlamydia

• •Chlamydia usually appears 5-12 days after birth
• •Treat with systemic erythromycin

Question 15

Neonatal Conjunctivitis / Ophthalmia Neonatorum

• Time frame
• organisms
• treatment

Answer 15

• 24-48 hours -> Gonococcal -> Penicillin
• 5-12 days -> Chlamydia -> Erythromycin

Question 16

45 year old female comes in for an exam

• •No complaints, just has a coupon for a free exam.
• •Let’s have a look!

***What immunoglobulins are responsible??

Answer 16

THYROID EYE DISEASE

• •Proptosis / exophthalmos
• •Lid retraction
• •Redness

•Why are the eyes o prominent?

• •Extraocular muscles and orbital soft tissues are infiltrated with antibodies.
• •Take up more space in the orbit and force globe forward
• •The immunoglobulins responsible are IgG
• •Treating the underlying thyroid condition does not treat the eye disease.

Question 17

A 30 year old female with a red left eye

• •36 hours duration (UNILATERAL)
• •Very painful
• •Light makes it worse (photophobia)
• •Let’s have a look!

Answer 17

Acute Iritis (Inflammation of Iris) aka Anterior Uveitis (Inflammation of anterior uveal tract)

• •Almost always unilateral
• •Photophobia is a hallmark
• •Ciliary flush (ring of red around cornea) is a hallmark
• •Most often idiopathic (not a cause we can identify)
• •Can be associated with RA, Lupus, HLA-B27, and other related conditions.
• •Vision is usually not affected

Question 18

30 year old male with red eyes

• •Both eyes red for three days, both eyes became red at the same time
• •They itch
• •His nose is runny
• •He’s sneezed a few times

Answer 18

ALLERGIC CONJUNCTIVITIS

• •Itching is most common symptom
• •Bilateral with simultaneous onset
• •Often associated with allergic rhinitis
• Conjunctiva pale (when you pull down bottom of eye). Remember that viral conjunctivitis will be very red.

Question 19

30 year old male with red eyes

• •Both eyes are red, but the right was red first, the left became red a couple of days later
• •They burn and feel swollen
• •Clear discharge
• •Works as a daycare employee, doesn’t wash his hands as much as he would like.

Answer 19

Viral conjunctivitis

• •Very contagious (often occurs in teachers)
• •Often bilateral, but assymetric (one eye first, then the other 2-3 days later)
• •Can be associated with swollen preauricular and submandibular lymph nodes
• •Not much itching
• •Clear discharge (described as tearing), no purulent discharge
• •Usually resolves spontaneously within about two weeks
• Conjunctiva very red (when you pull down bottom of eye). Remember that allergic conjunctivitis will be pale

Question 20

45 year old man, with painful, sticky red right eye

• •Bothering him for 3 weeks
• •Left eye is asymptomatic
• •Has a thick, mucopurulent discharge

Answer 20

Bacterial conjunctivitis

• •Mucopurulent discharge, often copius
• •Usually monocular
• •Not as contagious as viral
• •General requires antibiotic therapy for resolution (Fluoroquinolones are en vogue)

Question 21

44 year old lady with painful red eye OS

• •No complaints with the right eye
• •Pain is conctant, nothing makes it better or worse
• •Associated with head and Nauseau
• •Vision is “cloudy”

***Identify treatment

Answer 21

Angle closure glaucoma

• •More common in hyperopic eyes (eye is shorter so easier to become closed)
• •Very high pressure
• •Unilateral
• •Painful, but no photophobia
• •Decreased vision
• To understand it one must understand the fluid dynamics of the eye

**Angle is whre the trabecular meshwork is located

• •Treated with osmotic diuretics, LPI (laser peripheral iridotomy - make a hole so aqueous can get out and iris can fall back - relieve pain and vision returns )
• •Cornea is cloudy because of corneal edema due to increased pressure in anterior chamber of the eye in paticular
• •Trabechular outflow is blocked, so uveal-scleral outflow attempts to compensate (dilated episcleral veins/ red eye)

Question 22

3 unilateral eye conditions so far

Answer 22

• Acute Iritis (inflammation of iris)
• Bacteria conjunctivitis
• Angle closure glaucoma

Question 23

65 year old lady with a bump near the corner of her eye

• •Eye has had a lot of thick discharge
• •The eye has excessive tearing for several months
• •The bump is painful when she presses on it
• •It has gradually gotten larger

Answer 23

Dacryocystitis

• •A bacterial infection in the lacrimal sac
• •The cause is nasolacrimal duct obstruction
• •To understand dacryocystitis one must understand the nasolacrimal duct system.
• •Treat with antibiotics, possible drainage, and repair of the nasolacrimal duct obstruction

Question 24

35 year old man with painful red left eye

• •Has been red and painful ever since he splashed a cleaning solution in it 20 minutes ago.

•What do you do first?

• •History, check safety instructions on label and call poison control?
• •An exam to estimate which portion of the eye was most affected?
• •Determine allergies to possible antibiotics or anti-inflammatories?
• •Deduce why patient wasn’t wearing eye protection?
• •Determine pH of eye?

Answer 24

CHEMICAL INJURY

• FIRST THING IS COPIOUS IRRIGATION
• •History can be obtained after irrigation has commenced
• •Can read product label, contact poison control after irrigation has commenced
• •After the first litre of fluid has been dispensed, can check pH
• _•COPIOUS IRRIGATION IS THE FIRST THING ONE SHOULD DO!**********_

Question 25

25 year old with pupils that aren’t the same size

• •Noticed it while admiring his reflection in a brand new mirror
• •The term for pupils of different size is anisocoria
• •How do we know if the big pupil or the small pupil is the problem?
• •Anything else to consider?

Answer 25

HORNER’S SYNDROME; loss of sympathetic innervation

TRIAD (PAM)

• Ptosis
• Anhydrosis (no sweating in the forehead)
• Miosis (constricted pupil)

Pupils - Ptosis

• •What does sympathetic innervation cause the pupil to do? Dilation
• •What does parasympathetic innervation cause the pupil to do? Constrict
• •What is the source of Parasympathetic innervation of the pupil? Craniosacral – CN III
• •What is the source of sympathetic innervation of the pupil? Sympathetic chain ganglion
• •Why is the pupil miotic (small/ constricted) in Horner’s? Levator palpebrae superiosis innervated by sympathetics DO NOT WORK

Ptosis

• •What muscle raises the eyelid? Levator palpebrae and muellers muscle
• •What is it’s innervation? Sympathetics
• •Is that Sympathetic or parasympathetic?
• •Anything else? MUELLER’s MUSCLE

Mueller’s Muscle

• •Provides 2mm of lift/ elevation
• •Innervated by sympathetic nervous system
• •Application of epinephrine drops will reverse the ptosis in horner’s (will also dilate the pupil, but want help the un-sweaty forehead.)

Question 26

Identify movement disorders (6)

Answer 26

• •Parkinson’s
• •Huntington’s
• •Gilles de la Tourette
• •ALS
• •Alzheimer’s
• Multiple Sclerosis

Question 27

Describe Parkinsonism

• agents (meds used)

Answer 27

Parkinsonism

• •Progressive, neurologic disorder of muscle movement caused by loss of dopaminergic tracts in the substantia nigra

In Parkinson’s, loss of SN DA means:

­

• •Over activity of Indirect Pathway
  
  • •Resulting in increased glutaminergic output from the subthalmic nucleus
• Thalamic Input to motor cortex is reduced
• Bradykinesia, Rigidity

Question 28

Dopaminergic strategy (4)

Answer 28

• A.Precursor
• B.Enzyme inhibitors
• C.Dopamine agonists
• D.? Stimulates Dopamine Release / Storage / Synthesis

Question 29

Identify parkinson medication

• •Precursor of dopamine
• •Rapidly absorbed from GI tract if taken on empty stomach
• •Large doses required due to peripheral decarboxylation

**Identify side effects

**What is observed within 2 years of starting th medication??

Answer 29

LEVODOPA (L-Dopa)

•Side effects:

• –Nausea, Vomiting
• –Anorexia
• –Cardiac arrhythmias
• –Hypotension
• –Mydriasis
• –Visual, auditory hallucinations; over activity of DA at receptor
• –Dyskinesia; over activity of DA at receptor
• –Mood changes, depression, anxiety
• –Occasional psychotic

Dyskinesia observed within 2 years of starting L-Dopa therapy. Affects face, head, neck and limbs

Question 30

Levodopa (L-Dopa)

• On-Off Phenomenum
• Condraindications/cautions

Answer 30

Levodopa (L-Dopa)

•On-Off” Phenomenon

• –“On” associated with relief
  
  • •Improved mobility, often also associated with dyskinesia
• –“Off” during low levels of L-dopa
  
  • •Akinesia
• •Not seen in untreated patients
• •Not seen with other PD therapeutic agents

Contraindications

• •Do not give within 14 days of MAOI
  
  • –Potential for hypertensive crisis
• •Narrow angle glaucoma
• •Avoid high protein / high Pyridoxine (B6) diets
  
  • –B6 increases peripheral breakdown of L-Dopa, thereby diminishing its effectiveness
    
    • •Promotes decarboxylation
• •Avoid rapid discontinuation-syndrome similar to neuroleptic malignant syndrome
  
  • –agitated delirium with confusion
  • –Muscle rigidity (often extreme)
  • –Fever
  • –Autonomic dysfunction (tachycardia, high BP)

Question 31

Identify medication

• •Inhibitor of Aromatic L-amino acid decarboxylase
• •Does not cross BBB
• •↓ peripheral L-Dopa metabolism
• •↓ peripheral side effects of L-Dopa
• •No side effects
• •Reduces L-Dopa dose 10X

Answer 31

CARBIDOPA

• •Carbidopa/L-Dopa (Sinemet or Parcopa)

Question 32

Idnetify COMT inhibitors and how they work (2)

• which cross BBB? which does NOT? (work in periphery vs brain)

Answer 32

Catechol-o-methyl transferase (COMT) Inhibitors

Entacapone (Comtan) & Tolcapone (Tasmar)

• Inhibit metabolism of L-Dopa to 3-OMD (3-O-methyldopa).
  
  • Increases L-Dopa blood levels
  • 3-OMD also a competitive substrate for LNAA
    
    • Increases brain uptake
• Tolcapone crosses BBB and will inhibit central metabolism of dopamine

Question 33

COMT inhibitors (2)

• side effects
• which should you stop if you don’t see imporvement in 3 weeks

Answer 33

Entacapone (Comtan)

• •Adjunct to levodopa/carbidopa
  
  • –For patients who have signs/symptoms of end of dose “wearing off”
  • –L-Dopa/Carbidopa/Entacapone (Stalevo 50)
• •Side effects:
  
  • –Delayed diarrhea (2-12 weeks)
  • –Hallucinations (improved with lower levodopa levels)

Tolcapone (Tasmar) ; If no clinical improvement after 3 weeks of therapy (regardless of dose), discontinue tolcapone treatment

• •Inhibits peripheral and central COMT
  
  • –↑ CNS uptake of L-Dopa
  • –↓ frequency of “On-Off” phenomenon
    
    • •Diarrhea
    • •Fulminating hepatic necrosis
  • –Used as adjunct in patients receiving L-Dopa/Carbidopa
• Black box warning

Question 34

MAO inhibitors (2)

• effect on dopamine levels
• effect on DOPAC

Answer 34

Monoamine oxidase B inhibitors

• Selegline (deprenyl)
• Rasagiline (azilect)
• •Selectively inhibit MAO-B
  
  • –Increases dopamine levels
  • –Reduces DOPAC
    
    • •Reduces ROS in MPTP models

Question 35

MAO inhibitors (MAOI)

Selegline vs rasagiline

Answer 35

Selegiline (Deprenyl)

• •Reduces L-Dopa dose when used together
  
  • –Ameliorates “on-of”
• •Due to its selectivity, there is little potential for hypertensive crisis. Though at v high doses can inhibit MAO-A
• •Metabolized to amphetamine, potentiating effects of DA in brain
• •Large number of potential drug interactions
  
  • –Avoid meperidine
  • –Care with TCAs and SSRIs
    
    • •Can promote serotonin syndrome, though very rare
• –Avoid tryramine containing foods (antidepressant lecture for explanation)

Rasagiline (Azilect)

• •More potent than selegiline
• •Can be used as monotherapy in early stage patients
• •Adjunct therapy with Levodopa/carbidopa in advanced patients
• •Similar concerns as selegiline.

Question 36

Identify Dopamine Agonists (4)

• Side effects (table)

Answer 36

• •Bromocriptine (Cycloset)
• •Pramipexole (Mirapex)
• •Ropinirole (Requip)
• •Apomorphine (Apokyne)

Question 37

Identfiy dopamine agonist

• •Potent D2 agonist; Weak partial D1 agonist
• • Ergot derivative
  
  • –Used in combination with L-Dopa therapy
  • –Side effects which are more common than with L-Dopa limit its utility
  • –Can limit side effects by gradual build up of dose

Answer 37

Bromocriptine (Cycloset)

Question 38

Identify dopamine agonist (**Identify prominent side effects)

• •Newer therapeutic agents non ergot derivative so no link with valvular heart disease
• •Preferential affinity for D3 receptor
• •Absorbed rapidly orally
  
  • –No appreciable metabolism, renal excretion
  • –Lower dose for renal insufficiency patients
• •Used as a monotherapy in mild Parkinsons
• •Adjunct therapy in advanced parkinsonism in conjunction with levodopa
  
  • –Smooths out fluctuations in response
  • –Reduces levodopa dose

*****Identify another use

Answer 38

Pramipexole

•Prominent side effects

• –Nausea
• –Hallucinations
• –Insomnia
• –Dizziness
• –Constipation
• –Orthostatic hypotension

Also Used to treat Restless Leg Syndrome

Question 39

Identify dopamine agonist

• •Relatively specific to D2 receptor agonist
• •An extended release formulation also available
• • Effective monotherapy in mild Parkinsonism
• •Adjunct therapy for patients with advanced disease or response fluctuations

Answer 39

Ropinirole (Requip)

Question 40

Identify potent dopamine agonist

• •Potent dopamine agonist
• •Subcutaneous, rapid uptake to brain, clinical benefit in 10 min
• •Used as a rescue therapy or as continuous infusions to treat “off” episodes or levodopa-induced motor fluctuations
• •Nausea is very common
  
  • –Treat 3 days before with antiemetic such as trimethobenzamide, continue antiemetic for at least a month.
  • –Avoid serotonin agonist and dopaminergic antagonist based antiemetics

Answer 40

Apomorphine

Question 41

Identify

• antiviral drugs used in Parkinsons and also in drug induced extrapyramidal symptoms

*How does it work

*Side effects

Answer 41

• –Enhances DA synthesis & release; may inhibit reuptake
  
  • •Actual mechanism unknown
• –Side effects
  
  • •Restlessness
  • Orthostatic Hypotension
  • •Agitation
  • Urinary retention
  • •Confusion
  • Hallucinations, Dry mouth
• –High doses: acute toxic psychosis
• –Less efficacious than L-Dopa; side effects less severe
• –More effective than anticholinergics on rigidity, bradykinesia
• –Used in early stages or as a supplement to L-Dopa therapy

Question 42

Function of antimuscarinic agents

Answer 42

Decrease the excitatory actions of cholinergic neurons in the striatum by blocking muscarinic receptors

• Typically given to younger patients with initial mild tremors
  
  • •Trihexyphenidyl (prototype) – most common in US
  • •Benztropine
• •Adjunctive role in PD treatment
  
  • –Usually give as primary agents prior to introduction of L-Dopa
• Side effects: Cycloplegia, constipation, urinary retention, confusion, delirium, hallucinations

Question 43

Identify disease

• •Autosomal dominant disorder
• •Brain degeneration: cortex & striatum
• •Dementia, involuntary choreiform movements
• •↓GABA inhibition in striatum → hyperactivity of DA synapses
• •Treatment strategy is supportive care
• •Also to reduce dopamine input

***Agents used????

Answer 43

Huntington’s Disease (HD) aka “Huntington’s Chorea”

Reduction in cholinergic input, loss of GABA neurones

• •↓GABA inhibition in striatum → hyperactivity of DA synapses
• •Treatment strategy is supportive care
• •Also to reduce dopamine input
• •Death is usually due to progressive respiratory depression

Question 44

Identify HD drug

**Identify drug interactions and contraindications

• •Useful in mild forms of Chorea
• •Blocks dopamine reuptake in presynaptic vesicles
  
  • –Reduces dopamine released
• •Side effects dose dependant and mostly due to dopamine loss:
  
  • –Extrapyramidal symptoms, sedation, somnolence, fatigue, insomnia, akathisia, depression, anxiety, Parkinsonism
  • –Orthostatic hypotension, neuroleptic malignant syndrome, QTc prolongation, transaminases increased

Answer 44

Reserpine
Tetrabenazine (Xenazine)

• •Drug Interactions
  
  • –May enhance the QTc-prolonging effect of QTc-Prolonging Agents
  • –Enhance effects of other CNS depressants
  • –MAOI
• •Contraindications
  
  • –actively suicidal or with untreated or inadequately treated depression
  • –hepatic impairment
  • –use with or within 14 days of MAO inhibitors
  • –use with or within 20 days of reserpine

Question 45

Identify DA antagonist used in HD

Answer 45

• Chlorpromazine, Haloperidol, Typical antipsychotics (See antipsychotics lecture)
• Used in severe chorea and for treatment of associated psychosis

•Risperidone, Olanzapine Atypical antispychotics

• Treatment of milder chorea
• GABA agonists (Baclofen)

Question 46

Identify GABA agonists used in HD

Answer 46

• •Baclofen (Lioresal)
• •Antispasmodic, GABAB agonist
• •Acts as a muscle relaxant
  
  • –At the spinal cord inhibits the transmission of both monosynaptic and polysynaptic reflexes possibly by hyperpolarization of primary afferent fiber terminals resulting in antagonism of the release of putative excitatory transmitters
• •Pharmacokinetics:
  
  • –Limited metabolism
  • –Low and slow for the brain
• •Side effects:
  
  • –Drowsiness, vertigo, dizziness, psychiatric disturbances, insomnia, slurred speech, ataxia
  • –Muscle weakness
• •Drug Interactions:
  
  • –Can enhance CNS depression of other drugs
• •Contraindications / Warnings:
  
  • –Elderly patients may be more prone to CNS effects

Question 47

Identify disease

• Progressive neurodegeneration of motor neurons: muscle wasting, weakness, respiratory failure
• Familial forms of the disease exist- mutations in CuZnSOD enzyme

Answer 47

Amyotrophic Lateral Sclerosis (ALS)

• Primary treatment is supportive and treatment of major symptoms

Question 48

Identify treatment of ALS

• pharmacokinetics
• side effects
• contraindications/warnins

Answer 48

• •Riluzole (Rilutek)
  
  • –Approved for treatment of ALS slows progression (modestly)
  • –Mechanism of action unknown
  • –May protect from Glutamate neurotoxicity
    
    • •inhibition of glutamic acid release,
    • •noncompetitive block of NMDA receptor mediated responses
    • •direct action on the voltage-dependent sodium channel
  • –Prolongs time before life support is needed
• •Pharmacokinetics:
  
  • –Readily absorbed orally (90%), decreased by fatty foods
  • –Hepatic metabolism CYP1A2
• •Side Effects:
  
  • –Asthenia, diarrhea, dizziness, drowsiness increased hepatic enzyme levels, nausea vomiting, paresthesias, vertigo
  • –Potential for neutropenia
• •Contraindications / Warnings:
  
  • –Use caution in patients with hepatic impairment
  • –All patients should have regular liver enzyme panels

Question 50

Identify treatment options of alzheimer’s disease

Answer 50

Question 51

Describe Acetycholine Esterase Inhibitors in the use of alzheimer’s disease

****Examples (4), use and notes

Answer 51

Acetylcholine Esterase Inhibitors (AChEI)

•40-70% Inhibition shows clinical improvement

• •Cognitive improvement
• •Increased activation
• •Increased mood
• •Improved behavior

Question 52

Identify med

• •Used for treatment of moderately severe to severe AD
• •NMDA antagonist, Binds Mg site and thus blocks channel

Describe

Phamacokinetics

Side effects

Drug interactions

Cautions/warnings

Answer 52

MEMANTINE (Akatinol)

• •Pharmacokinetics:
  
  • –45% protein bound
  • –Elimination reduced by alkaline urine pH
• •Side Effects:
  
  • –Hypertension, Cardiac failure, TIA
  • –Dizziness, confusion, headache
• •Drug Interactions
  
  • –Carbonic anhydrase inhibitors may inhibit excretion
• •Cautions / warnings:
  
  • –Avoid drugs / diets that will change urine pH

Question 53

Identify drugs

1)

• •Slows progression of AD in several placebo-controlled trials
• •Recommendation: 1000 IU, twice daily

2)

• •Readily available at pet shops treats a fish parasite “ich”
• •Touted as a new wonder drug for Alzheimer’s
• •Potential for self medication
• •Strong MAOI

Answer 53

1. Vitamine E
2. Methylene Blue

Question 54

List the major physiological responses resulting from inhibition of acetylcholinesterase (AChE) - type of anticholinesterases

• Hydrolyze what???

Answer 54

Anticholinesterases (anti-ChE):

• •Acetylcholinesterase (AChE) hydrolyzes acetylcholine (ACh).
• •AChE is located at every ACh synapse.
• •Anticholinesterase (Anti-ChE) prevents the hydrolysis of ACh by AChE at sites of cholinergic neurotransmission
• •Results in the accumulation of ACh at muscarinic and nicotinic sites (ganglia, neuromuscular junction (NMJ), and effector targets).
• •Increases in ACh can induce stronger signaling at cholinergic sites; however, it can also lead to a depolarization block at ganglia and the NMJ.

Question 55

What is the structure of AChE and how does it hydrolyse ACh

Answer 55

• •Attachment of ACh to active site
• •Cleavage of ester bond
• •liberation of choline
• •forms acetylated enzyme - very unstable
• •rapid hydrolysis of acetylated enzyme liberation of acetate
• • formation of free, active AChE

Question 56

Describe the 3 MoA of Anti-ChE

• Which is reversible
• which include physostigmine?
• Which include edrophonium
• which is IRREVERSIBLE

Answer 56

1. Reversible Noncovalent Inhibitors
   
   • • Reversible
   • • Drugs; Edrophonium (short acting, quaernary amine), tacrine, donepezil
   • • bind to anionic site
   • • competes with ACh for anionic site
   • • Fast acting short duration
   • • Reversible
   • • Will lead to increases in ACh
2. Revesible Carbamate Inhibitors
   
   • • Reversible
   • • Drugs
     
     • o Physostigmine, neostigmine, pyridostigimine, rivastigmine
   • • They carbamylate esteratic site
   • • Slow hydrolysis of the carbamylating drug by AChE will lead to increases in ACh
3. Organophosphate compounds
   
   • DRUGS
   • o (isoflurophate (DFP), echothiophate) - higly lipophylic so have CNS effects of the eye *INSECTICIDES (malathion - treat headlice, diazinon, parathion) *NERVE GASES (tabun, sarin, soman)
   • • phosphorylate esteratic site - essentially irreversible
   • • regeneration of active enzyme requires hrs
   • • return of AChE activity depends on synthesis of new enzyme
   • • Stability of phosphorylated enzyme enhanced by “aging”.
   • • “Aging” occurs through the loss of one alkyl or alkoxy group which makes phosphorylated enzyme more stable - cannot be reactivated.

Question 57

Identify pharmacological effects of anti-ChEs (3)

Answer 57

• •Stimulation of muscarinic receptors
• •Stimulation followed by depression or paralysis of autonomic ganglia and skeletal muscle
• •Stimulation, with occasional subsequent depression, of cholinergic receptor sites in the CNS

Question 58

Identify pharmacokinetics of anti-AChEs

Answer 58

• -4 ° amines (will not cross BBB)
  
  • Edrophonium, neostigmine, pyridostigmine
• -High lipid solubility anti-AChEdrugs will cross the BBB
  
  • tacrine, rivastigmine, donepezil and organophosphate compounds

Question 59

Identify Clinical Uses of Anti-AChEs

***Identify the drugs based on the function

• Reverse atony of smooth muscle of intestine and bladder
• Chronic wide-angle glaucoma

Answer 59

• Reverse atony of smooth muscle of intestine and bladder
  
  • -40amines (neostigmine, pyridostigmine)
• Chronic wide-angle glaucoma.
  
  • -Also indicated for acute angle glaucoma (surgery indicated for long-term treatment).
  • -Long duration of action~1 week.
  • -Not first line therapy. Increase risk for cataract formation with prolonged treatment.
  • -Drugs (isoflurophate(DFP), echothiophate)

Question 60

Identify Clinical Uses of Anti-AChEs

***Identify the drugs based on the function

• Myasthenia gravis
• Reverse paralysis of NMJ blocking drugs
• Alzheimer’s disease

Answer 60

Myasthenia gravis

• Diagnosis (edrophonium)
• Treatment (neostigmine, pyridostigmine)

Reversal of the paralysis of competitive neuromuscular blocking drugs

• Neostigmine, pyridostigmine
• Use atropine to control the muscarinic effects (bradycardia)

Alzheimer’s disease

• Tacrine(has liver toxicity), rivastigmine, donepezil

Question 61

Describe the test of of Myasthernia gravis with the use of anti-AChEs TABLE ****

• Myasthernia crisis vs cholinergic crisis
  
  • Effect of edrophonium on muscle strength
  • Adjust Anti - ChE dose

Answer 61

Myasthenia gravis

• Autoimmune disease, antibodies against Nm destroys Nm at the NMJ, reducing muscle strength
• Edrophonium Test -myastheniccrisis vs. cholinergic crisis

Question 62

Identify toxic effects of anti-ChE

• toxicity
• muscarinic effects
• nicotinic effects
• chronic neurotoxicity

Answer 62

Toxicity

• Combination of parasympathetic and sympathetic effects.
• Muscarinic receptors, both types of nicotinic receptors, ganglia and skeletal muscle are involved.
• Activation of nicotinic receptors, followed by depolarization block.

Muscarinic effects: SLUD(E) + bronchoconstriction, blurred vision. Bradycardia with severe toxicity. Diminished vision and miosis. Sweating, excessive salivation. Hypotension (from the bradycardia).

Nicotinic effects at skeletal muscle

• Fatigability, generalized weakness, involuntary twitches, scattered fasciculations, and eventual severe weakness and paralysis.
• The most serious is paralysis of respiratory muscles.

Chronic neurotoxicity

• delayed neurotoxicity unrelated to cholinesterase inhibition
• certain organophosphates
• no specific therapy

Question 63

ANTIDOTE OF ANTICHOLINESTERASE POISING (2)

Answer 63

1. Atropine
   
   • Will reverse the muscarinic receptor affects, but has no effect at the nicotinic receptors
2. PRALIDOXIME (2-PAM) is a cholinesterase reactivator
   
   • Is used to reactive acetylcholinesterase following organophosphate anti-AChEpoisoning, but not carbamate or edrophoniumpoisoning.
   • •Pralidoximehas a very high affinity for the phosphate in the organophosphate and will pull the organophosphate off acetylcholinesterase.
   • •2-PAM must be given soon after the poisoning has occurred in order to prevent aging of the enzyme, at which point the enzyme cannot be reactivated

Question 64

Eye cont’d

66 year old male with double vision

• •Started when he awoke this morning
• •Goes away if he closes either eye

What causes diplopia?

Answer 64

DIPLOPIA

• •Monocular versus binocular (monocular is uncommon)
• •Ocular misalignment is called strabismus
• •What positions the eye?
• •What can cause acute strabismus in an adult? extaocular muscles?

Question 65

State the 6 extraocular muscles and their innervation

Answer 65

• •Superior Rectus – CNIII
• •Medial Rectus – CNIII
• •Inferior Rectus – CNIII
• •Inferior Oblique – CNIII
• •Lateral Rectus – CNVI
• •Superior Oblique – CNIV
• •Levator - CNIII

**Everything innervated by CNIII except lateral rectus (CN VI) and Superior Oblique (CN IV)

Question 66

66 year old male with double vision

• •Exam reveals Eye pulled out, SR, IR, MR don’t appear fully functional.
• •Eyelid is drooping about 4mm.
• •What nerve do we think is affected?
• •What is the pupil doing?

Answer 66

CN III palsy and pupil

• •We don’t know what the pupil is doing until we check!
• •The parasympathetic fibers that travel with CNIII have a separate nucleus and run along the outside of the nerve.
• •A microvascular cause (ischemia to the third nerve nucleus) will not affect the pupil.
• •A compressive cause will affect the pupil (what will that affect be?)

CNIII palsy with dilated pupil

• •Compression of the third nerve will cause a dilated pupil
• •Likely cause of compression is an aneurysm in the circle of Willis (pcom)
• •CNIII palsy with a dilated pupil is an emergency and requires neuro imaging

Question 67

Summarize CN III palsy

Answer 67

• •Normal pupil – likely microvascular (ischemic), not emergent
• •Dilated pupil – likely compressive (Post. Comm. Art. Aneur.), emergent!
• •For clarity – an aneurysm of the Posterior Communicating Artery IS NOT microvascular disease. The dilated pupil is caused by compression, not ischemia.

Question 68

86 year old lady with decreased vision os

• •Happened when she woke up yesterday
• •She has also had some unintended weight loss
• •It hurts when she brushes her hair
• •Has only been eating soup lately
• •Suspect anything?

Answer 68

Temporal arteritis / Giant cell arteritis

• •Inflammation of mid-sized arteries, giant cells will eventually obstruct the vessel lumen.
  
  • Branch of internal carotid obstructed so you have JAW CLAUDICAION - low blood supply to masseter for chewing,, obstruct ophthalmic artery (decreased vision)
• •What tests? CRP (C-reactive protein) and ESR (estimated sedimentation rate)
• •How to diagnose?
  
  • Elevated ESR ; not specific
  • Elevated CRP; not specific
  • Temporal artery biopsy
    
    • •This is the only definitive diagnosis
• •Treatment? Steroids - high dose prednisone
  
  • •Treat with steroids / immune modulators

Question 69

86 yo lady with decreased vision OS

• •Happened when she woke up yesterday
• •No weight loss
• •No scalp tenderness
• •Had a ministroke 6 months ago, but didn’t go to the doctor.
• •Lets have a look!

Answer 69

Retinal artery Occlusion

• •A thromboembolic event
• •Lack of perfusion due to a blockage from the inside

Question 70

86 yo lady with decreased vision OS

• •Happened when she woke up yesterday
• •No history of ministroke
• •No scalp tenderness, jaw pain, or weight loss
• •Has high blood pressure but doesn’t like to take her medicine (makes her feel tired)
• •Any thoughts?
• •Let’s have a look!

Answer 70

Retinal Vein Occlusion

• •the compression of a branch retinal vein by a branch retinal artery at an area of crossing (they share a common sheath where they cross)
• •The flow of the vein is blocked from the outside
• •High pressure in the artery compresses the vein (artery is always on top of vein. if arterial pressure of artery is very high, it can compress the vein)
• •Blood gets in, but it can’t get out.

Question 71

My child’s right eye looks red on facebook

• •Looking at a routine photo
• •One eye “glows red like a demon” in the photo
• •Any thoughts?
• •Let’s have a look!

Answer 71

Leukocoria (in golden angelic eye)

• •An absent or abnormal red reflex (white pupil is the derivation)
• •A lot of things can cause leukocoria, but only one of them is lethal
• •Any ideas? Retinoblastoma
  
  • ​•Retinoblastoma is the first condition you should think of when you see leukocoria
  • •Leukocoria is retinoblastoma until proven otherwise
  • •Cataracts, refractive error, and strabismus can cause leukocoria, but it is caused by retinoblastoma until proven otherwise.

Question 72

45 year old male with bilateral blurry vision

• •Getting worse for the past year
• •Has type 2 diabetes mellitus
• •Doesn’t check his blood sugar at home
• •Doesn’t know what his last blood tests showed
• •What do you think it is?
• •Let’s have a look!

***Identify type, what you see, treatment????

Answer 72

NPDR (Non-proliferative Diabetic Retinpathy)

• •No proliferation of blood vessels in the retina
• •Fluid leakage causes hard exudates (lipids), dot and blot heme and macular edema
• •Treat with focal laser treatment and/or anti-vegf injections

Question 73

45 year old male with bilateral blurry vision

• •Getting worse for the past year
• •Has type 2 diabetes mellitus
• •Doesn’t check his blood sugar at home
• •Doesn’t know what his last blood tests showed
• •What do you think it is?
• •Let’s have a look!

Answer 73

Proliferative Diabetic Retinopathy

• •Proliferation of new blood vessels
• •These new vessels can bleed (Vitreous Heme)
• •They can apply traction to the retina (tractional retinal detachment)
• •Also all the same things found in NPDR
• •Treated with pan retinal photocoagulation and/or anti VEGF injections.

Question 74

Describe diabetic retinopathy

Answer 74

Diabetic Retinopathy

• Loss of pericytes (vascular endothelial cells) leads leakage of liquids from the retinal capillaries
• •This leakage causes the edema and exudates in NPDR
• •Also, the loss of fluid leads to a relative ischemia of retinal cells
• •Ischemic retinal cells release VEGF (vascular endothelial growth factor)
• •VEGF causes new, abnormal, trouble making blood vessels to grow.
• •Can seem complicated, but it all starts with pericytes.
• •If you remember _loss of pericytes *(vascular endothelial cells)*,_ you can figure the rest out from there!

Question 75

45 year old with blurry vision

• •He’s not diabetic!
• •He can see pretty good at a distance, but having trouble reading lately.
• •Can see fine to read if he wears “cheaters” (OTC reading glasses)
• •Any thoughts?

Answer 75

Presbyopia

• •An emmetropic eye accommodates to see clearly at near.
• •The lens must change shape for this to occur.
• •As one ages, the lens loses elasticity (remember infoliation?)
• •Treated with reading glasses or bifocals.

Question 76

45 year old with blurry vision

• •Can see to read well, but can not see well at distance
• •What? Isn’t that the opposite of what one expects at age 45?
• •Any ideas?
• •Oh yeah, I had a retinal tear once.

Answer 76

Myopia

• •The optical system of the eye has too much plus power
• •Think of it as an eye that is “too long”; increased risk of retinal tear/ detachment
• •The eye provides excess convergence, need to add divergence (minus power) into the equation.
• •Minus powered glasses

45 year old with myopia

• •Glasses give great distance vision, but now he can’t read unless he takes off the glasses.
• •Oops! He does have presbyopia.
• •Bifocals add plus power to the minus power and fixes all.

Question 77

45 year old with blurry vision

• •I can’t see [expletive redacted] doc!
• •Can’t see up close or far away.
• •It’s been this way my whole life.
• •At least I’ve never had angle closure glaucoma.

Answer 77

45 year old with astigmatism

• •Astigmatism is an eye that is slightly cylindrical rather than spherical.
• •Think of it as football shaped rather than basketball shaped
• •More plus power in one axis, less plus power 90 degrees away
• •Cylindrical glass have more power along one axis (don’t forget the bifocal)

Question 78

45 year old with blurry vision

• •I can’t see [expletive redacted] doc!
• •Can’t see up close or far away.
• •I could see fine until I was thirty, but got a lot of headaches.
• •Oh, I had angle closure glaucoma once.

Answer 78

45 year old with hyperopia

• •The optical system of the eye does not have enough plus power
• •Think of it as an eye that is “too short”; increased risk of angle closure glaucoma
• •The eye does not provide enough convergence, need to add convergence
• •Young people can provide this plus power via accommodation, but it often causes headaches
• •Treat with plus power glasses, and we remember the bifocal this time.

Question 79

Summarize the 4 refractive errors

Answer 79

• •Myopia (near sighted) – “too long”
• •Hyperopia (far sighted) – “too short”
• •Presbyopia (bifocals) – “too old”
• •Astigmatism – “too cylindrical”
• •Not uncommon to have myopia plus astigmatism plus presbyopia
• •Not uncommon to have hyperopia plus astigmatism plus presbyopia
• •Anisometropia (one eye too short, one eye too long)

Question 80

65 year old with blurry vision

• •Gradual onset (not sure when it got bad, to be honest)
• •Worse at night, headlights on cars are so bad I don’t drive at night anymore
• •I argue with my spouse over colors (blue and white in particular)

Answer 80

Cataract (Nuclear Sclerotic Cataract/ NSC)

• •Gradual onset
• •Age related (everyone gets cataracts if one lives long enough)
• •Infoliation contributes
• •Glare is a common symptom
• •The color white may appear off-white, or cream, or tan
• •The color blue (as well as indigo and violet) short wavelength, most affected by passing through the cataract (this is just trivia)

Question 81

Cataract

• How do you treat it
• When do you treat it

Answer 81

• How to treat cataract - surgery
  
  • •The cataract is the lens
  • •Remove the lens
  • •Lens is encapsulated thats why it is infoliated so (Open the capsule)
• When to do the surgery
  
  • When it starts bothering them

Question 82

45 year old with tunnel vision

• •My peripheral vision is lousy
• •Noticed it while driving a school bus six months ago.
• •Lets check his visual fields!

Answer 82

Bitemporal Hemianopia

• •Lesion at the optic chiasm
• •Frequently a pituitary tumor
• •We will go over the pathways in a minute

Question 83

45 year old with tunnel vision

• •My peripheral vision is lousy
• •I noticed it while piloting a commercial airliner six months ago.
• •Let’s check the visual field!

Answer 83

Homonymous Hemianopia (same side affected on both sides i.e left side on both sides (temporal and nasal))

• •Lesion is somewhere beyond/posterior to the optic chiasm
• •Optic tracts, optic striations, visual cortex (often due to a cva or brain tumor)

Question 84

45 year old with tunnel vision

• •Peripheral vision is lousy
• •First noticed it while piloting a cruise ship 6 months ago.
• •Let’s check the visual field!

OR

45 y.o with tunnel vision

• •Right eye is completely blind (blacked out field)
• •Left eye is normal
• •This localizes to the optic nerve and/or retina (before the chiasm)

***Causes of visual defect

before chiasm? at the chiasm? beyond or posterior to chaism?

Answer 84

Question 85

5 year old failed vision screening

• •Failed a routine vision screening at the pediatrician
• •Parents haven’t noticed any decrease in visual function
• •Sometimes they do notice the left eye drifting out
• •Right eye: 20/20
• •Left eye 20/400
• •Ocular alignment appears normal
• •No abnormalities on slit lamp or fundus exam

Refraction (check for glasses)

• •OD: Plano (zero prescription) -> 20/20
• •OS: +6.50 -> 20/80 (for the life of me, I can’t get it to 20/20!)
• •Any ideas?

***Identify condition and causes (3) and treatment

Answer 85

Amblyopia (lazy eye?)

• •A condition in which both eyes fail to see the same thing with equal clarity.
• •This provides the visual cortex with discordant images
• •The brain neglects the input from one eye
• •If not corrected by 8 years of age this neglect becomes permanent

Amblyopia - causes

• •Anisometropia – a significant difference in refractive error in each eye
• •Strabismus – the eyes are pointing in different directions, see different images (diplopia in adults, amblyopia in children)
• •Deprivation – one eye is deprived of input (congenital cataract, severe refractive error, ptosis)

Amblyopia - Treatment

• •Proper vision correction (Glasses)
• •Correction of source of deprivation (remove cataract, repair ptosis)
• •Penalization – lessen the visual acuity in the preferred eye to force connections with the amblyopic eye
• •Correction of strabismus (more on this in a moment)

Penalization

• •Patching (simple, inexpensive and time tested, but sometimes the child does not cooperate.)
• •Pharmacologic – dilating drops (usually atropine), quick to administer, child cannot undo it, doesn’t work well for myopic children.

Question 86

Strabismus (Define)

• tropia
• phoria
• eso
• exo
• Hyper/hypo

**How to correct

Answer 86

Strabismus; misalignment of the eyes

• •Tropia – misalignment always present
• •Phoria – sometimes present (drifting eye)
• •Esotropia - crossed eye (looking inward)
  
  • •Correct with Eye Muscle Surgery (EMS)
  • •May be accommodative, correct with glasses in that case
    • Triad of accomodation - convergence, accomodation and miosis**​
• •Exotropia - corssed eye (looking outward)
  
  • •Correct with EMS
  • •Sometimes may treat with induced accommodation (over minus lenses)
• •Hyper/hypo; hyper means one eye is looking up. Hypo means eye looking down

Question 87

Glaucoma

• definition
  
  • •In broad terms, what is glaucoma?
  • •We’ve already talked about angle closure, but that is a less common type of glaucoma
• treatment
• causes

Answer 87

Glaucoma; Result of increased intraocular pressure – progressive optic NEUROPATHY

• •A progressive optic neuropathy that results for an intraocular pressure greater than the nerve can tolerate.
• •It can be different for different patients
• •Normal tension glaucoma
• •Ocular hypertension with no nerve damage

Glaucoma Treatment

• •The treatment of glaucoma is focused with lowering the intraocular pressure.
  
  • •Combination drops
  • •Drops that affect both aspects
  • •Drops + surgery
• •There are two ways to lower the intraocular pressure.
• •What do you think those two ways are?

Glaucoma causes

• •Increase aqueous outflow
• •Decrease aqueous production
• •This can be done with medication and/or surgery

Question 88

Norton

Define neurodegenerative diseases

Answer 88

• •Disorders characterized by the progressive loss of neurons, typically affecting groups of neurons with functional relationships even if they are not immediately adjacent
• •The pathologic process that is common across most of the neurodegenerative diseases is the accumulation of protein aggregates

Cerebrocortical Degeneration

• •Alzheimer Disease
• •Frontotemporal Lobar Degenerations - Pick Disease

Question 89

Identify neurodegenerative disease

• •Sixth leading cause of death
• •Most common dementia in elderly
• •10 - 15% are familial
• •Progressive loss of neurons in cerebral cortex
• •Decreased choline acetyltransferase and acetylcholine in cerebral cortex
• •Results in DEMENTIA
• •Etiology: Unknown
• •Diagnosis
  
  • •Clinical and brain imaging ID 80-90%
  • •Brain tissue required for definitive dx

Answer 89

Alzheimer Disease

• •Amyloid precursor protein (APP)
  
  • •Transmembrane
  • •May be cleaved to form Aβ peptide
• •Aβ peptide is critical to AD
  
  • •Two species: Aβ40 and Aβ42
  • •Aggregates easily
  • •Forms β-pleated sheets of amyloid
  • •Binds Congo red
  • •Resistant to breakdown
  • •Neurotoxic
• •Tau is critical in AD – microtubule-associated protein

Question 90

Genetics of Alzheimer disease

• what 4 chromosomes
• what cause early onset alzheimers
• what promotes Aβ generation and deposition

Answer 90

• •Abnormalities of Chromosomes 1, 14, 19, & 21
• •Amyloid Precursor Protein – chromosome 21
• •Down Syndrome (Trisomy 21)
  
  • •Gene dosage effect
  • •Alzheimer Disease in 3rd or 4th Decade
• •Presenilin-1 (chromosome 14)
• •Presenilin-2 (chromosome 1)
• •Mutations in these loci promote the generation of increased amounts of Aβ peptide especially Aβ42 via the γ-secretase complex
• •Result: early onset Alzheimer
• •ApoE (apolipoprotein E) – chromosome 19
• •3 alleles (ε2, ε3, ε4)
• •ε4 allele is seen more frequently in patients with Alzheimer disease
• •ApoE ε4 isoform promotes Aβ generation and deposition

Question 91

Describe morphology of Alzheimer disease

Answer 91

Alzheimer Disease Gross

• •ATROPHY of Cerebral Cortex
• •Thinned Gyri & Widened Sulci
  
  • •Frontal, Parietal &
  • •Medial Temporal Lobes
• •Cortical Gray Matter Thinned
• •Dilation of Lateral Ventricles (hydrocephalus ex vacuo)

Alzheimer Disease Microscopic

• •Neuritic Plaques
• •Neurofibrillary Tangles
• •Cerebral Amyloid Angiopathy

Question 92

Identify microscopic feature of alzheimer disease

Answer 92

•Neuritic plaques

• •20-200 µm
• •Contain tortuous neuritic processes
• •Central amyloid core with clear halo
  
  • •Aβ42 peptide is predominant component of core
• •Microglia and reactive astrocytes at periphery
• •Hippocampus, amygdala, neocortex – spares motor and sensory cortices

Question 93

Identify microscopic feature of what disease

• •Bundles of filaments in cytoplasm
• •Composed of paired helical filaments which contain abnormal protein tau (microtubule-associated protein)
• •Flame-shaped in pyramidal neurons
• •Silver stain
• •Insoluble, resistant to clearance, survive death of neuron

Answer 93

Neurofibrillary tangles

seen in Alzheimer’s disease

Question 94

what is microscopic feature ?

**WHat condition?

Answer 94

Cerebral Amyloid Angiopathy - in alzheimer’s disease

• •deposition of amyloid in walls of small meningeal and cortical arteries (amyloid is predominantly Aβ40)
• This picture shows a small vessel with a thickened wall due to amyloid deposition in a patient with Alzheimer dementia and amyloid angiopathy.

Question 95

Clinical Features of Alzheimer disease

Answer 95

• •A large burden of plaques and tangles is highly associated with severe cognitive dysfunction
• •With progression of disease, there is a loss of neurons and gliosis in the same areas of the brain with the most plaques and tangles
• •Usually >50 years of age
• •First, subtle changes
• •Loss of higher cortical function
• •Changes in mood and behavior
• •Then, disorientation, memory loss, aphasia
• •Then, can’t perform activities of daily living (ADLs)
• •Progression is over 10 – 15 years

Question 96

Treatment of Alzheimer disease

Answer 96

• •Some drugs help with symptomatic improvement, may delay requiring higher level of care by 1 – 2 years
• •No treatment stops the progression of the disease

Question 97

Identify condition

• •Heterogeneous set of disorders associated with focal degeneration of frontal and/or temporal lobes
• •Same frequency as AD in persons younger than 65 years old

***How do you diff from Alzheimer disease

Answer 97

Frontotemporal Lobar Degenerations (FTLDs)

• •Clinically distinguished from AD by alterations in personality, behavior and language preceding dementia
• Associated with cellular inclusions of two proteins, tau or TDP43 (FTLD-tau, FTLD-TDP)

Question 98

What is FTLD-tau disease called?

• presents at what age
• gross
• microscopic

Answer 98

FTLD-tau; PICK DISEASE

• •Usually presents at age 40 – 65 years
• •Gross
  
  • •Selective lobar atrophy of anterior frontal and temporal lobes – “knife-edge atrophy”
  • •Posterior 2/3rds of superior temporal gyrus, parietal and occipital lobes are usually preserved
• •Microscopic
  
  • •Most severe neuronal loss in outer 3 layers of the cortex
  • •Surviving neurons:
  • •May show characteristic swelling (Pick cells)
  • •May contain Pick bodies
    • •Round, slightly basophilic, cytoplasmic inclusions
    • •Contain tau
    • •Stain with silver
    • •Do not survive death of host neuron like neurofibrillary tangles in AD, not a marker of disease

Question 99

diff gross morphology of alzheimer disease vs Pick disease

Answer 99

Question 100

diff in microscopic in alzheimer vs pick disease

Answer 100

Question 101

Identify what and (3) types

• •Neuronal loss due to apoptosis or necrosis
• •In PD, 2% of neurons in substantia nigra are undergoing apoptosis vs. 0.5% in normal brain
• Mutations in gene for α-synuclein on chromosome 4q have been implicated - affect its folding / alter its structure

Answer 101

Basal ganglia Degeneration

• •Parkinson disease
• •Parkinsonism
• •Huntington Disease

Question 102

Identify Basal ganglia degeneration

• •Common (5% of Population >70)
• •Cause: Unknown
• •Depigmentation, neuronal loss, gliosis of PIGMENTED NUCLEI
  
  • •esp., Substantia Nigra, Locus ceruleus
• •Damages neuronal pathways from substantia nigra to corpus striatum
• • Dopamine in corpus striatum

Answer 102

Idiopathic Parkinson Disease

Question 103

Pathology of parkinson’s disease

• Gross
• Microscopic

Answer 103

• •Gross:
  
  • •DEPIGMENTED substantia nigra and locus ceruleus
• •Microscopic:
  
  • •Loss of dopaminergic neurons
  • •Gliosis of substantia nigra & locus ceruleus
  • •Lewy Bodies (eosinophilic cytoplasmic inclusions) in damaged cells (characteristic)

Question 104

Answer 104

Lewy Body

seen in Parkinson disease

Question 105

Clinical features of Parkinsons

Answer 105

TRAP; tremor, rigidity, akinesia/bradykinesia, postural instability

• •Usually occurs after age 50
• •Slowly progressive; extra-pyramidal dysfunction
  
  • •Cog-wheel rigidity
  • •Resting Tremor (Pill-Rolling)
  • •Bradykinesia
  • •Gait, festinating
• •Slow, difficult speech
• •Rx: Pharmaceuticals, deep brain stimulation, pallidotomy
• •Prognosis: POOR

Question 106

Describe dementia with lewy bodies

Answer 106

• 10-15% of patients with PD develop dementia
• Hallucinations and frontal signs
• Lewy bodies found in cortex
• May be a continuum
• 1. Lewy bodies in medulla
• 2. Lewy bodies in midbrain (PD)
• 3.Lewy bodies in cortex (dementia with Lewy bodies)

Question 107

Identify other causes of parkinsonism (3)

Answer 107

• •Postencephalitic Parkinsonism – seen after Spanish influenza 1915-1918
• •Drug side-effect – phenothiazines (anti-psychotic drugs), reserpine (reversible), MPTP (non-reversible)
• •Trauma – esp. repeated trauma, may see in boxers (Mohammed Ali)

Question 108

Describe rare, AD (autosomal dominant); Complete penetrance; delayed appearance

Answer 108

Huntington Disease

• •Due to an abnormality in the HD gene, on short arm of chromosome 4
• •The HD coding region contains CAG trinucleotide repeats, normally about 11 to 34 such repeats
• •Abnormal HD genes have increased number of repeats
• •The more repeats the earlier the onset.

Question 109

Huntington disease

• Morphology; gross vs microscopy
• Symptoms

Answer 109

•Morphology

• •Loss of Neurons & Atrophy
  
  • •Caudate Nucleus
  • •Putamen
  • •Variable cerebrocortical atrophy
• •Microscopic – severe loss of striatal neurons

Symptoms

• •Presents at 20-50 years of age
• •Dementia and psychotic sx (Cerebrum)
• •Choreiform Movements (Basal Ganglia)
• •Progressive
• •Death in 10-20 years after onset

Question 110

Describe Spinocerebellar Degeneration

Answer 110

• •Group of genetically distinct diseases
• •Most AD some AR
• •Affect cerebellum, brainstem, spinal cord, peripheral nerves
  
  • •Neuronal loss in affected areas
  • •Corresponding sx: ataxia, spasticity, sensorimotor peripheral neuropathies

Question 111

Example of spinocerebella degeneration

Answer 111

•Friedreich Ataxia

•Genetics

• •AR
• •Trinucleotide repeat disorder (GAA)
• Results in a protein deficiency (frataxin

•Degeneration of spinocerebellar tracts, posterior columns, pyramidal tract, peripheral nerves

•Late childhood/pre-adolescence

•Motor and sensory symptoms:

• •Gait ataxia, clumsiness, dysarthria
• •Weakness, loss of deep tendon reflexes
• •Impaired joint position and vibratory sense

•Other symptoms: Pes cavus, kyphoscoliosis, cardiac disease, DM (10%)

Question 112

Cont’s of fry eye

what ways can you decrease production in glaucoma (2)

what methods (2)

Answer 112

• •Increase aqueous outflow
• •Decrease aqueous production
• •This can be done with medication and/or surgery

Usually treated with a little of both

• •Combination drops
• •Drops that affect both aspects
• •Drops + surgery

Question 113

My mother had Bell’s palsy

• •When I was a second year medical student, my mother experienced Bell’s palsy.
• •What is it?
• •How does it affect the eye?

Answer 113

Bell’s palsy

• •CNVII palsy
• •CNVII innervates the muscles of facial expression
• •Also innervates both the lacrimal and salivary glands
• •Lagophthalmos – incomplete closure of the eyelids
• •Due to lack of innervation to the orbicularis oculi
• •Treat with lubrication, tape lid closed, surgical repair with lid weights
• •What about lacrimal gland?
• •Aberrant re-innervation of lacrimal gland
• •Fibers intended for the salivary gland find their way to the lacrimal gland
• •“crocodile tears”

Question 114

Define the risks

1)

• •A farmer near the equator
• •Or a surfer in San Diego

2)

• •A person with 6 diopters of hyperopia
• •That is a very hyperopic eye

Answer 114

1. Ptergium
2. Angle closure glaucoma

Question 115

Fenger - virus infections of the eye

Identify symptoms of primary infections of the eyes

Answer 115

Viruses from a number of different families are capable of causing primary infections of the eye. They may cause an infection of the cells covering the surface of the cornea which is designated as keratitis. Some viruses infect the cells of the conjunctiva which form a membrane covering the inner surface of the eyelid and the sclera of the eye. Another manifestation of the infection is keratoconjunctivitis which involves infection of both the corneal surface and the conjunctiva.

Question 116

Identify viruses that cause primary infections in children and adults (8)

• Family
• Genome
• Capsid
• Envelope

Answer 116

Question 117

What viruses cause infection of the eyes of the fetus as a result of congenital infections. These include:

Answer 117

Question 118

Herpesvirus infection of the eye

• primary infections
• recurring infections
• latent infections
• secondary infections

Answer 118

Herpesvirus infection of the eye

• Certain viruses of the herpesvirus family can cause primary and recurring infections of the eye. The exact nature and frequency of the recurrences seems to depend, in part, on the strain of herpes simplex virus that causes the primary infection as well as the immune status and general health of the individual. Note: HSV1 and HSV 2 exist in a variety of strains that differ in their pathogenicity. Herpes simplex virus (HSV) will serve as the primary point of discussion. Recall HSV exists as two types, 1 and 2.
• After primary infection, HSV induces a latent infection in the trigeminal ganglia (usually HSV 1) or in the sacral ganglia (usually HSV 2). In the case of trigeminal latency the virus can be reactivated from the latent state, travel down the ophthalmic branch and cause secondary infections of the eye.

Question 119

Disease manifestations of primary and recurring infections of the eye by HSV

• layers of the eye and functions
• IMPORTANCE OF ENDOTHELIAL CELLS

Answer 119

Primary and recurring infections of the eye by HSV may cause various disease manifestations. In certain situations the viral infection can be exacerbated by an immuopathological attack against the eye. Different anatomical features of the eye may be involved in the infectious process.

Recall (see diagram) that the outermost layers of cells covering the cornea constitute the epithelium. Underneath the epithelium is the stromal layer which is composed of keratocytes (fibroblastoid) and an orderly array of collagen fibers. The parallel alignment of the fibers ensures optical clarity and maximum transmission of light.

The innermost layer of cells is the endothelial layer which functions as a osmotic pump to keep the stromal layer dehydrated. If the stromal layer is no longer functioning, the stroma become hydrated and assumes a milky white appearance contributing to corneal blindness.

Question 120

How does PRIMARY HSV INFECTION of eye present as?

The pattern of infection varies dependent on what?

How do you visualize lesions on the cornea of the eye?

some strains of HSV cause what broader lesions?

Answer 120

Primary HSV infection of the eye usually presents as blepharoconjunctivitis (HSV infection of eye lids and conjunctiva) and superficial punctate keratitis, both of which heals without significant scarring. Less frequently primary infections of the cornea begins with replication of the virus in the epithelial cells composing the outermost layers of the cornea.

The pattern of infection varies depending on the strain of HSV 1 and HSV2 that initiated the infection. Some strains cause a pattern of cell destruction that looks like a “winding stream” or a dendrite and this is referred to as dendritic keratitis. The ophthalmologist can best visualize these lesions using a fluorescent dye and shinning a blue light on the eye to observe the fluorescent lesion (see below).

Alternatively Rose Bengal can be applied to the eye and this causes the lesion to appear pink in color. A special device, slit lamp microscope, can help observe the lesions optimally.

Some strains of HSV cans cause broader lesions on the surface of the eye, which has been label geographic ulcers because they look like a continent on the surface of the earth.

Question 121

After the primary HSV infection resolves, the individual may have recurring infections over time.

• what lesions occur as result of some HSV strains and immunological based pathogenicity?
• What do this ulcers lead to?
• when do patients become candidates for corneal transplants
• what results from HSV infection of iris and surrounding tissues . Inflammation, sensitivity to light, blurred vision, pain, and eye redness.
• what is also possible by rare in occurrence

Answer 121

• Some HSV strains, in conjunction with immunological based pathogenicity occurring in the patient, may cause the development of infections that involve infection of keratocytes in the stromal layer of the cornea. This leads to stromal ulcers. When the infection resolves the keratocytes synthesize new collagen fibers that are not arranged in an orderly array, i.e. scarring. After repeated stromal infections the scarring may be significant and cause loss of visual acuity.
• One of the most severe manifestations of eye disease is called “corneal melting”. This appears to have an immunopathological basis whereby the immune systems attacks the stromal layer of the cornea. Following HSV infection the antigens of the virus that are present in the stroma elicit infiltration of the stroma by PMNs which are activated to produce complement and other products. Macrophages and activated T cells follow which causes further damage. In some cases treatment with steroids can exacerbate the destruction. The endothelial cell layer is often destroyed and the corneal becomes hydrated. Recurring HSV infections of the cornea is the most frequent cause of corneal blindness in developed countries
• Patients with advanced corneal scarring and corneal melting are candidates for corneal transplants. However, the latent virus is still resident in the trigeminal ganglia and its reactivation can start the infectious process of the cornea all over again.
• Iridocyclitis results from HSV infection of iris and surrounding tissues . Inflammation, sensitivity to light, blurred vision, pain, and eye redness.
• Herpes retinitis is also possible but rare in occurrence.

Question 122

What eye infections can result from Herpes varicella-zoster virus (3)

Answer 122

Herpes varicella-zoster virus can cause an infection of the conjunctiva primarily but it can also involve a corneal infection as part of a primary infection.

• Herpes zoster ophthalmicus can also represent the recurrence of a latent infection from the trigeminal ganglia.
• This may also lead to uveitis and optical nerve palsies.

Question 123

• Identify eye infection from CMV (herpes virus)
• eye infection from rubella virus (Togavirus)

Answer 123

• CMV (Herpesvirus) can also cause a chorioretinitis following the infection of the fetus as a result of a congenital infection. This may result in cataract formation and microphthalmia. In AIDS patients CMV has been shown to cause chorioretinits
• Rubella virus (Togavirus) like CMV can cause a fetal infection. The viral infection stunts the growth of tissues. And cataracts result from the infection.

Question 124

Identify eye infections from the following viruses

• Adenoviruses types (DNA virus)
• Enterovirus 70 and Coxackie A24
• Newcastle disease virus

Answer 124

• Adenoviruses types (DNA Virus) 3,7,8, and 19 can cause keratoconjuctivitis. Adenovirus is very resistant to inactivation (UV light and drying conditions) in the environment and can remain viable for days to weeks in water. Eye infections have been documented from inadequate chlorination of swimming pools for example. Adenovirus has also been demonstrated to cause epidemics of keratoconjunctivitis in naval shipyards which is designated “shipyard conjunctivitis”
• Enterovirus 70 and Coxackie A24 (Picornaviruses) can cause a hemorrhagic conjunctivitis and this particularly seen in the tropics.
• Newcastle disease virus (Paramyxovirus) is usually a virus that infects chickens but farmers occasionally acquire the disease (zoonosis)

Question 125

• General Anesthetics
• Inhalational anesthetics
• Halogenated (5) vs Non-Halogenated (1)

Answer 125

• •General Anesthetics: Reversible state of loss of sensation and consciousness
• •Inhalational Anesthetics: Gases or volatile liquid

Question 126

General anesthesia “the ideal”

Answer 126

• •Amnesia (so you don’t remeber the surgery to avoid PTSD - propofol, aka milk of amnesia?)
• •Analgesia (don’t feel pain - opiods)
• •Produce state of consciousness or unresponsiveness
• •Block sensory and autonomic reflexes
• •Skeletal muscle relaxation (not respiratory muscles)
• •Rapid induction and emergence
• •Wide window of safety
• • “Balanced Anesthesia”

Question 127

Pharmacokinetics - Inhalation Anesthetics

• how is potency expressed
• MAC definition (equivalent to?)

***what is MAC affected by? Not affected by?

Answer 127

• •Potency expressed as minimum alveolar concentration (MAC)
• •MAC (minimum alveolar concentration): inspired concentration of anesthetic required to produce anesthesia in ½ of subjects.
  
  • –Equivalent to ED50
  • –Expressed as % of inhaled gas

Question 128

MAC is affected by? (4)

Answer 128

• –Age: MAC is for a 35-40 year old
  
  • •­ increased infancy/childhood;
  • •decreased old age
• –Health Status:
  
  • •­ increased hyperthyroidism;
  • •decreased hypothyroidism
• –Drug Interactions:
  
  • •decreased Sedatives;
  • •­ increased Amphetamines
• –Red Hair ­INCREASED
  
  • Red hair is less susceptible to anesthesia

Question 130

Anesthesia Induction

Answer 130

Question 131

Describe how rate of induction changes based on condition

• Increased gas vs decreased gas
• Ventilation
• solubility
• CO

Answer 131

Cardiac Output

• A higher cardiac output removes more volatile anesthetic from the alveoli and lowers therefore the alveolar partial pressure of the gas. The agent might be faster distributed within the body but the partial pressure in the arterial blood is lower. It will take longer for the gas to reach an equilibrium between the alveoli and the brain. Therefore, a high cardiac output prolongs induction time

Question 132

Concentration vs partial pressure

Answer 132

Anesthetic Induction occurs faster with agents which are less soluble in blood

Question 133

MAC vs effective dose

**Identify anesthetics types in order of MAC

•A linear relationship exists between lipid solubility and MAC.

**Idnetify types based on solubility

Answer 133

Question 134

MoA of anesthetics

Answer 134

• •Meyer-Overton Theory: Anesthetic dissolves in the membrane and “affects” the function of membrane proteins – no specific receptor, no specific antagonist
• •Agents may interact with hydrophobic regions of proteins embedded in lipid bilayer of neuronal membranes
• •Anesthetics may impede the breakdown of GABA
• •Potentiation of GABA-increased Cl- influx
• •Increase K+ efflux; Reduce Na+, Ca2+ influx

Question 135

Identify halogenated anesthetia

• •Potent anesthetic
• •Weak analgesic
• •Blood:gas partition coefficient (2.3)
• •Usually coadministered with nitrous oxide, opioids, local anesthetics
• •Has a pleasant odor
• •Do not repeat at intervals less than 2-3 weeks

(((CV effects, resp effects, metabolism

**what drug is it combined with?

• treatment???????

Answer 135

Halothane

• •Halothane + succinylcholine
  
  • –increased risk of malignant hyperthermia
  • –sustained contraction of skeletal muscles; dramatic increase in O2 consumption;
    
    • •­ body temperature
    • •effects due to the inability of the sarcoplasmic reticulum to sequester Ca2+
• •Treatment: dantrolene

Question 136

Identify anesthesia

• •Less potent than halothane
• •Rapid induction/recovery
• •Pleasant odor

**Identify CV and esp effects

Answer 136

Enflurane

Question 137

effects of enflurane

• muscular effects
• CNS effect
• metabolism

Answer 137

Question 138

identify halogenated anesthesia

• •Smooth/rapid induction and recovery
• •Pungent odor
• •Structural isomer of enflurane

Answer 138

Question 139

Identify halogenated anesthesia

•Very rapid induction/recovery

Answer 139

Desflurane

Question 140

halogenated anesthesia

• New drug
• Rapid induction/recovery
• Low pungency
• Similar to desflurane

Reacts with soda lime in breathing apparatus at low flow rates, requiring special equipment

Leads to production of toxic compound, Compound A: (pentafluoroisopropenyl fluoromethyl ether)

Fl- release during metabolism; potential for toxicity

Answer 140

Sevoflurane

Question 141

NON-halogenated anesthesia

• •Potent analgesic
• •Weak anesthetic
• •“Balanced Anesthesia”
• •Rapid induction/recovery

Answer 141

NITROUS OXIDE (N2O)

Question 142

Describe second gas effect

• what is often used?

Answer 142

• •A rapidly absorbed gas INCREASES the rate of uptake of a 2nd anesthetic gas
• •Concentration of gas 1 is high
• •As this volume of gas disappears from the lung, fresh gases are literally sucked into the lung from the breathing circuit to replace the volume taken up.
• •Rate of uptake of gas 2 is therefore higher

Nitric Oxide often used

Question 143

Elimination of Inhalation anesthetics

• Major route
• metabolism in liver
• halide ions cause?
• Anesthetics with low blood solubility

Answer 143

• •Major route: lungs
• •Metabolism in liver → release of halide ions
• •Halide ions can cause toxicity (hepatic/renal)
• •Anesthetics with low blood solubility are eliminated at a faster rate than those with high blood solubilities

Question 144

IV anestheti agents

• •Used for rapid induction of anesthesia which is then maintained with inhalation agent
• •Preanesthetic sedation
• •Induction
• •Perioperative analgesia
• •Anesthesia for minor procedures

•Agents used include:

• –Others
• –Barbiturates
• –Benzodiazepines
• –Opioids

Question 145

FANTASTIC Anesthesia for OUTPATIENT SURGERY

***efects of drug

**Mechanism

Answer 145

• –For induction and maintenance
  
  • • 2-8 min for distribution
  • • 30-60 min for elimination
• –Less hangover, more rapid recovery
• –Cardiovascular and respiratory depression
• –Not analgesic
• –Amnesia “milk of amnesia”
• –Used for same day surgical procedures

Question 146

Propofol

Answer 146

• •Propofol-related infusion syndrome (PRIS) is a serious side effect with a high mortality rate characterized by dysrhythmia (eg, bradycardia or tachycardia), heart failure, hyperkalemia, lipemia, metabolic acidosis, and/or rhabdomyolysis or myoglobinuria with subsequent renal failure.
• •Concomitant Opiate use may lead to increased sedative or anesthetic effects of propofol, more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output. Lower doses of propofol may be needed. In addition, fentanyl may cause serious bradycardia when used with propofol in pediatric patients.
• •Alfentanil use with propofol has precipitated seizure activity in patients without any history of epilepsy.

Question 147

Identify short tem vs long term effects of propofol

Answer 147

• •Short-term effects
  
  • •oblivion and a feeling of being slowed down and spaced out. disinhibition followed by a feeling of calm and an upbeat mood.
  • •mild euphoria, hallucinations
• •Long-term
  
  • •addiction

Question 148

Identify anesthesia

• –Non-barbiturate for induction
• –Minimal cardiovascular effects
• –Decrease cerebrovascular blood flow to brain
• –Advantage for brain/neural type surgeries
• –Not analgesic
• –Post-op nausea and vomiting

Answer 148

ETOMIDATE

Question 149

Barbiturates

• examples
• use
• recovery from drug
• Complications

Answer 149

Barbiturates

• •Examples: Thiopental, methohexital, thiamyl
• •Ultra-short acting
• •Used for induction
• •Used for sedation
• •Recovery from thiopental is due to redistribution from the brain into less vascular regions (muscle, skin)
• •No antagonist in case of overdose
• •May cause a transient rise in BP
• •Thiopental may result in hypotension, circulatory collapse and cardiac arrest in cases of hypovolemia, circulatory instability, sepsis, toxemia or shock
• •Barbiturates can depress respiration
• •Contraindicated:
  
  • –Variegate porphyria
  • –Acute intermittent porphyria

Question 150

Benzodiazepines (BDZs)

• examples
• use
• complication
• ANTAGONIST

Answer 150

Benzodiazepines (BDZs)

• •CNS depressants
• •Examples: Diazepam, lorazepam, midazolam
• •Anxiolytic
• •Amnesiac
• •Sedative
• •Antiepileptic
• May depress respiration
• Increase frequency of channel opening

BDZ Antagonist: Flumazenil

Question 151

Identify Opiods for anesthesia (3)

• use
• can cause?
• Opiod antagonist (rescue drug)

Answer 151

Opiods

• •Fentanyl, Morphine, Sulfentanil​
• •Used to induce analgesia
• •Used in cardiac surgery as cardiac output and myocardial contractility are preserved
• •Can cause: Hypotension, respiratory depression, muscle rigidity, postanesthetic nausea/vomiting
• •Remember potential for interaction with propofol or gaseous anesthetics mentioned earlier

•Opioid antagonist i.v. NALOXONE (opiod antagonist)

Question 152

Anticholinergics

• uses
• examples (3)
• which is more effective than atropine at preventing salivation
• which is less effective than atopine at preventing reflex bradycardia

Answer 152

Anticholinergic

• •Used to combat secretions
• •Used to prevent vagal effects
• •Atropine, scopolamine, glycopyrrolate
• •Scopolamine is more effective at preventing salivation than atropine
• •Scopolamine is less effective than atropine at preventing reflex bradycardia

Question 153

Identify anticholinergics

• Long acting
• Less sedating than scopolamine
• Better antisialogogue than atropine
• Produces less tachycardia
• More effective in preventing bradycardia
• Does not cross BBB
• Causes peripheral effects

Answer 153

Glycopyrrolate

Question 154

Identify mental state where individual appears to be dissociated from environment without complete loss of consciousness

Answer 154

Dissociative Anesthesia

Ketamine:

• •chemically/pharmacologically related to phencyclidine (PCP)
• •Mechanism: Block NMDA receptor
• •Induction agent / Dissociative anesthesia
• •Profound Analgesia
• •Can also increase CBF and potentially ICP

Recovery (reduces utility)

• –delirium, hallucinations, irrational behavior can occur in adults; less likely to occur in children

Question 155

Identify Stages of Anesthesia (4)

Answer 155

•Stage I: Analgesia

• –Patient is conscious and conversational

•Stage II: Excitement

• –Patient experiences delirium and violent, combative behavior
• –Increase in blood pressure
• –Tachycardia
• –Increase in respiration
• –Mydriasis
• –Increase in skeletal muscle tone; urinary and or fecal incontinence

NOTE: Goal of anesthesiologist is to keep the duration and intensity of this stage to a minimum

Short acting barbiturate given IV before inhalation anesthesia to avoid Stage II

Stage III: Surgical anesthesia

• –Regular respiration: Eye movements cease, become fixed:
• –Relaxation of skeletal muscle:

–Stage IV: Medullary paralysis

• –Severe depression of respiratory and vasomotor centers
• –Death

Question 156

Goal of local anesthetics

• ester drugs vs
• amide type drugs

Answer 156

•Goal: To create loss of sensation without loss of consciousness or impairment of central control of vital functions

Question 157

Local anesthesia

• Structure
• MoA

Answer 157

Local anesthesia

Structure

• Amine, weak base
• Ionized form predominates at low pH
• Inflammation/acidosis decrease tissue pH

MoA

• •Reversible inhibition of axonal nerve conduction by binding to Na+ channel
• •Bind on internal site of Na+ channel
• •Ionized anesthetic has more affinity for channel
• •Prolongs inactivation state of channel
• •Once bound, drugs greatly restrict conformational changes that underlie activation

Small, unmyelinated fibers more easily anesthetized: autonomic and sensory nerves blocked easier than motor neurons:

• –Pain
• –Temperature
• –Touch
• –Sympathetic vasomotor activity inhibited before proprioception
• –Muscle tone
• –Somatic motor activity
• –Nerves recover in reverse order

Question 158

Local anesthetics

• Duration of action
• Metabolism
  
  • Ester
  • Amide
• Adverse effects

Answer 158

•Duration of action

• –Determined by rate of diffusion/absorption (determined by chemical properties, local pH, blood flow)

•Metabolism

• –Ester type drugs: Esterases, plasma cholinesterases
• –Amide type drugs: Amidases, liver
• –Urinary excretion of metabolites

Adverse effects ;

•If absorbed into systemic circulation, local anesthetics can have:

• –CNS effects
  
  • •CNS stimulation (restlessness, tremor, euphoria, clonic convulsions) [inhibition of inhibitory neurons] followed by CNS inhibition (sedation, drowsiness)
  • •Headache, paresthesias, nausea, seizures followed by coma
  • •Death occurs by respiratory failure
• –CV effects
  
  • •Hypotension
  • •Cardiac depression
• –Hypersensitivity reactions
  
  • •Allergic dermatitis or asthmatic attack
  • •Usually due to ester anesthetics due to metabolism to PABA (allergic)

Question 159

Effect of vasoconstrictors on local anesthetics

Answer 159

• •Vasoconstrictors prolong effects of local anesthetics
  
  • •Epinephrine, phenylephrine
• •Slows rate of absorption; decreases drug plasma concentration
• •Less likelihood of side effects
• •Should not be used in anesthetizing tissues with end arteries (fingers, toes, ears, nose, penis). Sympathomimetic amines increase oxygen consumption of tissue-coupled with vasoconstriction-hypoxia results-potential tissue damage. Gangrene could occur.
• •Should not be used in patients in whom adrenergic stimulation may have an adverse effect (hypertensive, ventricular arrhythmias)

Question 160

Indications of topical anesthesia

• where and what drug

Answer 160

•Topical Anesthesia

• –Skin (Benzocaine)
• –Mucous membranes, cornea (Tetracaine, lidocaine, cocaine)
• –Epinephrine – no significant local effect; can’t penetrate mucous membranes

Mixtures of Anesthetics:

• –LET: Lidocaine, Epinephrine, Tetracaine
• –EMLA: Eutectic mixture of lidocaine and others

Question 161

Indications for infiltration anesthesia

Answer 161

•Infiltration Anesthesia

• –Anesthetic injected directly into tissues
• –Dental procedures, minor surgical procedures
• –Epinephrine doubles duration of anesthesia
• –Disadvantage: Large amounts of drug used to anesthetize small areas

Question 162

Indications of Iontophoresis

Answer 162

•Iontophoresis

• –Small electrical current forces anesthetic into a tissue
• –Used in dentistry

Question 163

Describe field block anesthesia

Answer 163

• Administered in a series of injections to form a wall of anesthesia encircling operative field
• Advantage:
• Less drug for greater area of anesthesia than infiltration

Question 164

Describe Nerve block Anesthesia

Answer 164

• Injected into or adjacent to a nerve or nerve plexus
• Example: (Brachial plexus – upper extremity; Intercostals – anterior abdominal wall; Cervical plexus – neck)
• Produces large area of anesthesia with small amount of drug; even better than field block or infiltration

Question 165

Describe spinal anesthesia

Answer 165

• •Injection into lumbar subarachnoid space below the level at which the cord terminates
• •Spread of anesthetic in CSF controlled by horizontal tilt of patient and specific gravity of anesthetic. Hyperbaric solutions used (density > CSF)
• •Can be used for people contraindicated for general, for lower body (knee etc) surgery

Question 166

Describe epidural anesthesia

Answer 166

• •Injection into lumbar or caudal epidural space
• •Bupivacaine used for labor/delivery
• •Absorbed into systemic circulation; has to be monitored closely to prevent cardiac depression and neurotoxicity in mother/neonate

Question 167

Describe ester type local anesthetic

Answer 167

COCAINE

• •Ester type local anesthetic
• •Only local anesthetic that causes vasoconstriction
• •Controlled substance; subject to abuse
• •Used topically to anesthetize the internal structures of the nose, ear, throat

Question 168

Identify anesthetics

1)

• •1st synthetic local anesthetic - Ester
• •Short duration (20-45 min)
• •Parenteral administration
• •Metabolized to PABA

2)

• •Ester
• •Pruritus
• •Eardrops
• •Teething/gum pain
• •Supplied as lozenges for pharyngitis
• •Treatment of sunburn

Answer 168

1. Procaine (Novacain)
2. Benzocaine (Americain)

Question 169

ANesthetic

•Amide

• –Metabolized in liver
• –Monoethylglycinexylidide & glycinexylidine
• Topical/parenteral administration
• Infiltration, nerve block, epidural, spinal anesthesia
• Intermediate duration (60-120 min)

Answer 169

Lidocaine (Xylocaine)

Question 170

• •Lidocaine congener
• •Metabolized to O-toluidine
• »
• Can cause methemoglobinemia
• •Limited to topical/infiltration anesthesia
• •Half life > Lidocaine

Answer 170

Prilocaine (Citanest)

Question 171

• Obstetrical anesthesia
• Cardiotoxic
• –Decreases threshold for tachycardia

•Half life ~ 300 minutes

Answer 171

Bupivacaine (Marcaine)

Question 172

Norton Cont’d - demyelinating disease

Describe motor neuron disease

• degeneration of what?
• is it purely motor or purely sensory or non of the above
• Loss of what? (3)

Answer 172

• •Degeneration of BOTH
  
  • Upper & Lower Motor Neurons
• •Purely MOTOR
• •Loss of:
  
  • 1.Upper motor neurons in cerebral (motor) cortex
  • 2.Degeneration of corticospinal tracts in lateral spinal cord (lateral sclerosis)
  • 3.Lower motor neurons in brain stem and spinal cord (anterior horn)

Question 173

Describe degenerating diseases based on morphology

• •Gross: thinned ventral roots of spinal cord
• •Microscopic: Upper motor neuron destruction leads to degeneration of myelin in corticospinal tracts
• • ↓ neurons in anterior horn throughout length of spinal cord, loss of anterior root myelinated fibers
• •Skeletal muscles show neurogenic atrophy

Answer 173

Amyotrophic Lateral Sclerosis (ALS)

The lateral sclerosis in the name of this disease (amyotrophic lateral sclerosis) refers to the loss of the lateral corticospinal tracts on the left and on the right in the spinal cord. This microscopic picture shows the pallor of the descending (lateral) corticospinal tracts when stained for myelin. The Betz cells in the motor cortex are affected in this disease and when they die the tracts degenerate.

This is a close up of a myelin stain to show the corticospinal tract degeneration in amyotrophic lateral sclerosis (ALS). Both the axons and myelin degenerate secondary to neuronal loss in the motor cortex of the cerebrum.

There is progressive loss of neurons in the anterior horn cell area in amyotrophic lateral sclerosis (ALS). This view of the anterior horn in the lumbar cord shows only a few remaining large neurons. The small nuclei in the background represent the astrocytes which have reacted to the neuronal cell loss.

With loss of anterior horn cells there is neurogenic atrophy in the skeletal muscles. Note the group of atrophic fibers in the center. There has also been reinnervation of the fibers superiorly by a neuron which was still viable.

Question 174

ALS

upper motor vs lower motor neuron signs

Answer 174

• •Results in upper motor paralysis of extremities
  
  • •Skeletal muscle neurogenic atrophy (amyotrophic)
  • •Hypertonia of muscles
  • •Exaggerated deep tendon reflexes
• •Lower motor neuron signs
  
  • •Muscle weakness
  • •Eventual paralysis of respiratory muscles

Question 175

ALS

• epidemiology
• symptoms; early vs endstage
• Prognosis, progression and treatment

Answer 175

ALS - Amyotrophic lateral Sclerosis

Epidemiology

• •Most cases are sporadic, 5-10% familial (AD, SOD1 gene, chromosome 21)
• •Men > women
• •Usually older than 50 years old

Clinical

•Early:

• •Asymmetric weakness of hands
• •Cramping and spasticity of arms and legs
• •Muscle atrophy
• •Fasciculations

•Endstage:

• •Deficits of both upper and lower motor neurons

•Prognosis:

• •50% 5-year survival, usual cause of death is bronchopneumonia secondary to muscle paralysis
• Progression: Variable
• Treatment: symptomatic and riluzole (glutamate antagonist)

Question 176

Describe Spinal Muscular Atrophy (Type 1,2,3)

• which type is most serious

Answer 176

•SMA Type 1 (Werdnig-Hoffman disease_); **Most serious_

• •AR – deletions of survival motor neuron gene (SMN), chromosome 5
• •Loss of motor neurons in anterior horns of spinal cord →
• Atrophy of anterior spinal roots & peripheral motor nerves →
• Denervation & atrophy of skeletal muscle groups

•Clinical: congenital hypotonia (“floppy baby”), relentless course resulting in majority of patients dying within first year of life

•Types 2 & 3 – later onset of muscle weakness, more protracted clinical course

Question 177

Demyelinating diseases

• •Episodes of neurologic deficits separated in time, attributable to white matter lesions separated in space
• •Most common autoimmune, inflammatory, demyelinating disorder
• •Any age, 20-40 y.o. most common, F:M, 2:1

***Pathogenesis

Answer 177

Multiple Sclerosis

Pathogenesis

• •Initiated by TH1 and TH17 which react against myelin Ag (cellular immune response)

•Genetics:

• •Risk associated with HLA DRB1 locus
• •Siblings of affected person: 3-5% risk
• •Monozygotic twin of affected person: 20+% risk

•Environment

• •Incidence varies geographically
• •More common in temperate latitudes – 30-50x more common in U.S., Canada, and northern Europe
• •1:1000 in U.S. and Europe

Question 178

Describe morphology of multiple sclerosis

• active vs inactive plaques vs shadow plaques

Answer 178

•PLAQUES in the White Matter

• •Size Varies
• •Adjacent to lateral ventricles, optic nerves and chiasm, brain stem, cerebellum, & spinal cord
• •Sharp Borders

•ACTIVE Plaque

• •Myelin breakdown, fewer oligodendrocytes
• •Abundant macrophages containing myelin degradation products
• •Lymphocytes (B and T), plasma cells, monocytes (perivascular)
• •Axons fairly preserved

•INACTIVE Plaques

• •Little or NO myelin
• •Prominent astrocytic proliferation & gliosis
• •Axons without myelin and diminished in number
• •SHADOW Plaques*
• •Border between normal & affected white matter NOT Sharply Circumscribed

•Some plaques are silent, found at autopsy

Question 179

MS - clinical features

Answer 179

•Certain s/s are common

• •Unilateral vision impairment from optic nerve involvement
• •Brain Stem
  
  • •Ataxia, nystagmus, internuclear opthalmoplegia
• •Spinal Cord
  
  • •Motor & sensory impairment, spasticity, bladder dysfunction

Question 180

Identify condition

• seen in what condition

Answer 180

Internuclear ophthalmoplegia

• •Seen in multiple sclerosis
• •When pt is asked to look to left, left eye moves to left and exhibits jerk nystagmus, right eye remains stationary

Question 181

MS (multiple sclerosis) - CSF content

• Why is gamma globulin increased? proliferation of what?

Answer 181

• •Mildly elevated protein
• •Moderate lymphocytes and neutrophils in about 1/3 of patients
• •Gamma Globulin Increased
  
  • •Oligoclonal Bands
  • •Due to proliferation of B cells in nervous system

Question 182

Identify condition based on pathogenesis and morphology

• •Abs to aquaporin-4, the major H2O channel of astrocytes
• •Abs injure astrocytes through complement-dependent mechanisms
• •Areas of demyelination also show loss of aquaporin-4

Answer 182

Neuromyelitis optica

Clinical

• •F >> M
• •Bilateral optic neuritis
• •Prominent spinal cord involvement

Question 183

Identiify demyelinating disease

• •Caused by rapid correction of hyponatremia
• •Acute hyponatremia (present < 48 h) can cause cerebral edema
• •Brain adapts correcting the cerebral edema in 2 to 3 days OR
• •If hyponatremia develops slowly then brain adapts before development of cerebral edema
• •Adapted brain is vulnerable to injury from rapid correction of hyponatremia

Answer 183

Central Pontine Myelinolysis aka Osmotic Demyelination Syndrome

•Pathogenesis – not well understood

• •Adaptation involves loss of electrolytes (Na+, K+, Cl-, myoinositol, glutamine and glutamate) and water which protects from cerebral edema
• •After rapid correction of hyponatremia, brain shrinks and cannot rapidly replace lost electrolytes
• •In animal models, areas of the brain which replace electrolytes most slowly are the ones that undergo the most demyelination

Question 184

Central Pontine Myelinolysis aka Osmotic Demyelination Syndrome

• Identify clinical signs and symptoms

Answer 184

•Clinical

• •Sx: Dysarthria, dysphagia, lethargy, confusion, paraparesis, quadriparesis, disorientation, obtundation, coma, or “Locked in”
• •Symptoms may be only partially reversible
• •Symptoms appear 2 – 6 days following rapid correction

•Usually seen in rapid correction of hyponatremia <120 mEq/L

The muscles of the mouth, face, and respiratory system may become weak, move slowly, or not move at all after a stroke or other brain injury. A person with dysarthria may experience any of the following symptoms, depending on the extent and location of damage to the nervous system:

• “Slurred” speech
• Speaking softly or barely able to whisper
• Slow rate of speech
• Rapid rate of speech with a “mumbling” quality
• Limited tongue, lip, and jaw movement
• Abnormal intonation (rhythm) when speaking
• Changes in vocal quality (“nasal” speech or sounding “stuffy”)
• Hoarseness
• Breathiness
• Drooling or poor control of saliva
• Chewing and swallowing difficulty

Question 185

Central Pontine Myelinolysis aka Osmotic Demyelination Syndrome

• Morphology
• at risk patients
  *

Answer 185

•Morphology

• •Symmetrical Loss of Myelin – diffuse or in brain stem, pontine tegmentum
• •Periventricular and subpial regions preserved

•At risk patients:

• •Alcoholism
• •Severe Electrolyte or Osmolar Imbalance
• •Liver Transplant

Question 186

Metabolic diseases are due to what 2 conditions

Answer 186

• •Nutritional Diseases
• •Metabolic Disturbances

Question 187

Identify nutritional diseases

• •Associated with beriberi
• •May cause Wernicke encephalopathy (psychosis); if untreated then
• •Korsakoff (Memory disturbances, confabulation) – largely irreversible

**Seen in what conditions

Answer 187

Thiamine (B1) Deficiency

•Seen in:

• •Chronic Alcoholism
• •Gastric Disorders (CA, chronic gastritis, or persistent vomiting)

Question 188

Identify condition

• what nutritional deficiency?

Answer 188

Wernicke Korsakoff - Mammillary Bodies

Thiamine deficiency - Morphology

• •MAMMILLARY Bodies
  
  • •Focal Hemorrhage and Necrosis
    
    • •Also of 3rd and 4th Ventricles
• •Memory Disturbances caused by
  
  • •Lesions in Medial Dorsal Nucleus of the Thalamus
• •Treatment: thiamine

Question 189

Identify nutritional deficiency

• •Ataxia
• •Parasthesias of Lower Extremities
• •Spastic Weakness to Paraplegia
• •Degeneration of AXONS
  
  • •Ascending Tracts (Posterior Column)
  • •Descending Pyramidal Tracts
  • •“Subacute Combined Degeneration of the SPINAL CORD”

Answer 189

B12 Deficiency

Question 190

Identify metabolic disturbances

• •Resembles hypoxia
• •Neurons sensitive to hypoglycemia & ischemia
  
  • •Large pyramidal neurons of the ctx
  • •Hippocampus (Sommer Sector)
  • •Cerebellum (Purkinje Cells)
• •If prolonged and severe, many areas may be affected

Answer 190

HYPOGLYCEMIA

Question 191

Identify metabolic disturbances

• •Uncontrolled D.M. with
  
  • •Ketoacidosis (DM-1) -OR-
  • •Hyperosmolar Coma (DM-2)
• • →Dehydration
• •Rehydration may cause cerebral edema
• •RESULT: Confusion, Stupor, Coma
• •Rx: SLOW Rehydration to prevent cerebral edema

Answer 191

HYPERGLYCEMIA

Question 192

Identify condition

• •Cellular response primarily glial
• •Alzheimer type II astrocytes seen in hyperammonemia
• •NO Abnormalities in the Neurons

Answer 192

Hepatic Encephalopathy

Question 193

Toxic disorders

• similar to hypoxia??*****
• Clinical
• Labs
• treatment

Answer 193

•Carbon monoxide**** – similar to hypoxia

• •Affects same cells as hypoxia (which are? - purkinje cells, pyramidal neurons of hypocampus?) as well as
• •Bilateral necrosis of globus pallidus
• •Demyelination

•Clinical - cherry red tongue

• •Low levels – HA, dizziness, abdominal pain, nausea
• •Higher levels – confusion, dyspnea, syncope, permanent neurologic deficits in survivors of severe poisoning
• Carbon monoxide
• Lab – carboxyhemoglobin saturation
• Rx
• •Supportive
• •High concentration of O2
• Carboxyhemoglobin (COHb) is a stable complex of carbon monoxide and hemoglobin that forms in red blood cells when carbon monoxide is inhaled. COHb should be measured if carbon monoxide or methylene chloride poisoning is suspected. COHb is also useful in monitoring the treatment of carbon monoxide poisoning.*
• The reference range of COHb differs among smokers and nonsmokers, as follows:*
• Nonsmokers: Up to 3%*
• Smokers: Up to 10%-15%*

Question 194

Identify toxic disorder

•Pathology

• •Degeneration of retinal ganglion cells (may be due to metabolite)
• •Selective bilateral putamenal necrosis
• •Focal white matter necrosis
• Clinical – altered mental state
• Lab – anion gap metabolic acidosis
• Treatment – fomepizole (blocks alcohol dehy’ase) OR EtOH (competes for alcohol dehy’ase)

Answer 194

METHANOL

Question 195

Identify toxic disorders

• Acute – altered mental status, ataxia, dyscoordination
• Chronic – cerebellar dysfunction in 1%, truncal ataxia, unsteady gait, nystagmus
• Pathology??????

Answer 195

ETHANOL

• •Atrophy and loss of granule cells in anterior vermis
• •Advanced cases: Loss of Purkinje cells with proliferation of adjacent astrocytes

Question 196

Toxic disorders

Radiation

• Pathology
• Clinical

Answer 196

•Radiation

•Pathology

• •Coagulative necrosis affecting all elements of white matter: astrocytes, axons, oligodendrocytes, blood vessels; with adjacent edema
• •Can induce tumors years after RT

•Clinical – HAs, nausea, vomiting, papilledema

Question 197

Normal Peripheral Nerve

• Motor unit
• Nerve fiber
• Axons
• Myelination

Answer 197

•Motor unit

• •Functional unit of the neuromuscular system
• •Composed of lower motor neuron, axon, muscle fibers

•Nerve fiber

• •Structural component of peripheral nerve
• •Composed of axon, Schwann cells and myelin sheath

•Axons

• •Contain organelles
• •No protein synthesis – proteins are delivered from perikaryon

•Myelination

• •Myelinated in segments known as internodes, one Schwann cell per internode
• •Internodes are separated by nodes of Ranvier
• •Myelin protein zero makes up >50% of PNS myelin protein

Question 198

Normal Peripheral Nerve

• Nerve
• Connective tissue components

Answer 198

•Nerve

• •Multiple nerve fibers grouped into fascicles by connective tissue sheaths (myelinated and unmyelinated together)

•Connective tissue components

• •Endoneurium – surrounds individual nerve fibers
• •Perineurium – encloses each fascicle
• •Epineurium – encloses entire nerve

Question 199

Peripheral nerve pathology

***describe segmental demyelination vs remyelination

Answer 199

• •Segmental Demyelination
  
  • •Dysfunction of the Schwann cell or damage to myelin sheath (no primary abnormality of the axon)
  • •Disintegrating myelin - engulfed by Schwann cells then macrophages
• •Remyelination
  
  • •New internodes are shorter
  • •New myelin sheath is thinner
• •Repeated sequential demyelination and remyelination:
  
  • •Schwann cell processes whirl around the axon
  • •Cross-section shows layers of Schwann cell cytoplasm and basement membrane around a thinly myelinated axon (onion bulb)

Question 200

Peripheral nerve pathology

• Describe •Axonal degeneration and subsequent muscle fiber atrophy

Answer 200

•Axonal degeneration and subsequent muscle fiber atrophy

• •Axonal damage
  
  • •Due to focal events such as trauma, ischemia OR
  • •Generalized abnormality affecting the neuron cell body or its axon
• •Injury due to a focal lesion results in wallerian degeneration distal to the lesion
  
  • •Axon breakdown starts in first 24 hrs
  • •Affected Schwann cells 1) catabolize myelin then 2) engulf axon fragments
  • •Macrophages phagocytose axonal and myelin-derived debris
• •Axonal degeneration and muscle fiber atrophy (cont.)
  
  • •May not see evidence of axonal degeneration in slowly developing neuronopathies because few fibers are actively degenerating at any one time
  • •Muscle fibers in the affected motor unit undergo atrophy because of loss of their neural input (denervation atrophy)
  • •Stump of proximal axon shows degenerative changes of only the most distal internodes then undergoes regenerative activity

Question 201

Explaine Nerve regeneration (General reactions of the motor unit)

Answer 201

•Nerve Regeneration

• •Proximal stumps of degenerated axons sprout and elongate, developing new growth cones
• •Growth cones are guided by vacated Schwann cells
• •Histologic evidence of regeneration is the presence of the regenerating cluster: Multiple closely aggregated, thinly myelinated small-caliber axons
• •Regeneration is slow: ~1mm/day, limited by the axoplasmic movement of tubulin, actin and intermediate filaments

Question 202

Diseases of peripheral nerve

•characterized by inflammatory infiltrates in peripheral nerves, roots, ganglia

Answer 202

Inflammatory Neuropathies

• •Immune-mediated neuropathies

Question 203

Give example of Immune-mediated neuropathy

Answer 203

•Guillian-Barré Syndrome (Acute inflammatory demyelinating polyradiculoneuropathy)

• •Life-threatening
• •1-3 cases/100,000 in US
• •Characterized by weakness beginning with distal muscles rapidly progressing to proximal muscles

Question 204

GBS (Guillian-Barre Syndrome)

• Pathogenesis
• Morphology

Answer 204

•Pathogenesis

• •Two-thirds of cases are preceded by an acute influenza-like illness (or vaccination) and pt has recovered before onset of neuropathy

•Morphology

• •Inflammation of peripheral nerve (infiltration by lymphocytes, macrophages, and a few plasma cells)
• •Segmental demyelination is primary lesion; macrophage cytoplasmic processes peel away myelin from axon then engulf myelin
• •Remyelination follows demyelination

Question 205

GBS - gullian barre

Clinical Course

Answer 205

•Guillian-Barré Syndrome (cont.)

•Clinical course - Ascending paralysis

• •Loss of deep tendon reflexes
• •Sensory involvement may be detected
• •Nerve velocity is slowed
• •Elevation of protein in CSF from inflammation and altered permeability of the microcirculation within the spinal roots
• •Pts may spend weeks in ICU before recovering normal function
• •Mortalitiy 2-5% (down from 25%) from respiratory paralysis, autonomic instability, cardiac arrest, and complications of treatment

Question 206

Diseases of peripheral nerve

• Give example of infectious polyneuropathies
  
  • Which type is seen with Symmetric polyneuropathy

Answer 206

•Infectious Polyneuropathies – Leprosy

• •Lepromatous leprosy
• •Schwann cells invaded by Mycobacterium leprae
• •Segmental demyelination and remyelination
• •Loss of axons
• •Endoneurial fibrosis
• •Symmetric polyneuropathy
  
  • •Involves pain fibers
  • •Results in loss of sensation leading to injuries and large traumatic ulcers on extremities

Question 207

Identify types of leprosy

1. symmetric polyneuropathy
2. •Cell-mediated immune response to M. leprae manifested by nodular granulomatous inflammation in the dermis

• Cutaneous nerves in the vicinity of the inflammation are injured; axons, Schwann cells, myelin are lost
• Fibrosis of perineurium and endoneurium
• Patients have more localized nerve involvement than in Lepromatous leprosy

Answer 207

1. Lepromatous leprosy
2. Tuberculoid leprosy

Question 208

Identify infectious polyneuropathies

• •Latent infection of neurons in the sensory ganglia of the spinal cord and brainstem following chickenpox
• •Reactivation leads to a painful, vesicular skin eruption in the distribution of sensory dermatomes
• •Morphology: Neuronal destruction and loss, mononuclear inflammatory infiltrates, regional necrosis with hemorrhage. In peripheral nerves see axonal destruction after death of sensory neurons

Answer 208

•Varicella-Zoster Virus (Shingles)

• Acutely, Herpes zoster virus infects the dorsal root ganglia. This picture demonstrates a hemorrhagic lesion of acute herpes zoster in a dorsal root ganglion of an immunosuppressed patient who developed “shingles” (a dermatomal distribution of skin vesicles) two weeks before death. The latent form of herpes zoster will remain dormant in the dorsal root ganglia for years after the initial infection with chicken pox (varicella zoster virus) and then can activate into an acute lesion.
• Once Herpes zoster virus is reactivated, the pink to mauve viral intranuclear inclusions may be seen in the satellite cells around the ganglion cells in the dorsal root ganglion. The virus travels distally down the axon to the periphery, causing the vesicular skin eruption known as shingles. Thus, involvement of a dorsal root ganglion gives rise to the typical dermatomal distribution of the skin lesions.

Question 209

Identify •Acquired Metabolic and Toxic Neuropathies

• DIABETICS

Answer 209

Peripheral Neuropathy in Adult-Onset Diabetes Mellitus

• •Overall 50% of diabetics have peripheral neuropathy
• •80% of patients with diabetes for > 15 years
• •Nearly 100% have conduction abnormalities
• •Different manifestations
  
  • •Distal symmetric sensory or sensorimotor neuropathy
  • •Autonomic neuropathy
  • •Focal or multifocal asymmetric neuropathy

Question 210

Peripheral Neuropathy in Adult-Onset DM(cont.)

• •Morphology

Answer 210

• •Axonal neuropathy – seen in patients with a distal symmetric sensorimotor neuropathy
• •Segmental demyelination
• •Endoneurial arteries with thickening and hyalinization
• •Whether lesions are due to ischemia or metabolic derangements is unclear

Question 211

Peripheral Neuropathy

• Clinical Course

Answer 211

Peripheral Neuropathy in Adult-Onset DM (cont.)

•Clinical Course

• •Symmetric neuropathy is most common
• •Patients develop decreased sensation in distal extremities, motor abnormalities are less evident
• •Loss of pain sensation results in development of ulcers that heal poorly because of diffuse vascular injury
• •Dysfunction of the ANS affects 20-40% of diabetics, nearly always associated with distal sensorimotor neuropathy

Question 212

Identify traumatic neuropathies

Answer 212

•Transection

• •Regeneration can still occur slowly
• •Regrowth complicated by discontinuity between the proximal and distal portions of the nerve sheath as well as by the misalignment of individual fascicles
• •Axons may continue to grow resulting in a mass of tangled axonal processes known as a traumatic neuroma
• •Within a traumatic neuroma small bundles of axons appear randomly oriented but are surrounded by organized layers of Schwann cells, fibroblasts and perineurial cells

Question 213

Identify traumatic neuropathies

• •Most common entrapment neuropathy
• •Results from compression of median nerve at the level of the wrist within the compartment delimited by the transverse carpal ligament
• •Women > men
• •Frequently bilateral
• •Symptoms: numbness and paresthesias of tips of thumb and first two digits

Answer 213

•Compression neuropathy (entrapment neuropathy)

• •Carpal tunnel syndrome

Question 214

Identify •Compression neuropathy (entrapment neuropathy) - 4

Answer 214

• Carpal tunnel Syndrome
• •Ulnar nerve at elbow
• •Peroneal nerve at knee
• •Radial nerve in upper arm

Question 215

Identify hereditary neuropathies

Answer 215

•Hereditary motor and sensory neuropathies (HMSN)

• •Most common form of hereditary neuropathies
• •Affect both strength and sensation
• •Present as spectrum of disorders all caused by mutations in genes involved in formation and maintenance of myelin

Question 216

Example of hereditary neuropathies

• •Most common hereditary peripheral neuropathy
• •Presents in childhood or early adulthood
• •Patients may be asymptomatic or show symptoms of distal muscle weakness, atrophy of the calf muscle, orthopedic problems of the foot

***Genetics

Answer 216

HMSN I – Charcot-Marie-Tooth Disease, hypertrophic form

•Genetics: Heterogenous

• •Chromosome 17p11.2-p12 duplication resulting in segmental trisomy of duplicated region. Peripheral myelin protein 22 is encoded in the duplicated region (most common defect, 70-90%)
• •Chromosome 1 has locus with myelin protein zero
• •Chromosome 16p

Question 217

HMSN I – CMT Disease, hypertrophic form (cont.)

• Morphology
• Clinical course

Answer 217

•Morphology

• •Demyelinating neuropathy
• •Histology shows multiple “onion bulbs” from repetitive demyelination and remyelination
• •Hypertrophic neuropathy
  
  • •Layers of Schwann cell surround individual axons
  • •Peripheral nerves are so enlarged that they may be palpable

Clinical course

• •AD
• •Slowly progressive
• •Disability of sensorimotor deficits and associated orthopedic problems are usually limited in severity
• •Usually have a normal lifespan

Question 218

•1. Become comfortable with sideline evaluation/diagnosis of concussion including SCAT-5use

Answer 218

SCAT (sideline concussion assessment tool); rapid neurologic screen

• •Balance assessment
• •Ocular movement
• •Cranial Nerves
• •Coordination
• •Gait
• •Reading
• Orientation/memory/cognition
• Balance/BESS testing
• Timed tandem gait
• King-Devick testing

Question 219

•2. Familiarize practitioner with standard office management of concussion and return to play

***When do you consider post concussive syndrome (timeframe)

Answer 219

When in doubt; SIT THEM OUT - DON’T LET THEM PLAY

• •WHEN IN DOUBT, SIT THEM OUT
• •Weekly follow up until asymptomatic
  
  • –Loosened up depending on school/ATC
• •Exams including GCS, typically < 13 worse outcome
  
  • –Anisocoria
• •Repeat symptom scores weekly
  
  • –As part of SCAT, IMPACT
• •NEED to modify school environment
  
  • –Excuse HW, tests, no notes, allow early exit, H/A breaks, ½ days, sunglasses, leave class 10 min early, leave school if persistent
• •Upon week 3, begin to consider post concussive syndrome
  
  • persistence of concussion (at 21 days - age 5 to 18)

Question 220

•3. Familiarize practitioner with testing modalities such as IMPACT, King-Devick, neuropsych testing

Answer 220

King-Devick testing

• •Falling into more favor
  
  • –Well researched in MMA, newer studies presented at AMSSM San-Diego with good support in collision sport environment
• •Easy to implement
  
  • –PAPER BASED
• •Quick sideline test
  
  • •1-2 minutes.

•Tests:

• –Cognition
• –Attention
  
  • •Unrecognized but definite component of concussion
• –Saccadic eye movement
  
  • •Horizontal and vertical
• –Mental fatigability
• –Ability to follow commands

Neuropsych Testing (2 froms)

–Formal

• •Performed and interpreted by neuropsychiatrist
• •Will isolate out specific cognitive deficits to base tx plan upon
• •Standard for post concussive syndrome

–Computer based

• •In-office
• •$$$
• •Useful as a “tool” but not definitive at this point
• •IMPACT, CogSport, C3Logix, ANAM, Head Minder
• •Little evidence, primarily from private industry

imPACT testing (normal is 0.2-0.6??)

• •Baseline vs. post injury
  
  • –DO NOT HAVE TO HAVE BASELINE
• •Cognitive efficiency index
  
  • Smart kids can mask concussion by doing well in cognitive impact test. So focus more on their symptoms.
• •6 batteries of tests
  
  • –Verbal Memory
  • –Visual Memory
  • –Visual Motor Speed
  • –REACTION TIME
  • –Impulse control
  • –Symptom score

Question 221

•4. Familiarize practitioner with post-concussion syndrome and management

Question 222

•5. Introduce controversial/future topics such as chronic traumatic encephalopathy, serologic testing

Answer 222

Chronic traumatic encephalopathy,

• •Initially thought to extend to repetitive injury
• •Motor control issues
  
  • –Parkinsonian
• •? Emotional control centers
  
  • –Depression, Alcoholism, Suicide, Schizophrenia

Serologic testing

• •The next “holy grail” if a POC test can be developed (cardiac enzymes)
• •No definite markers accepted yet
• •Multiple different markers in industry
  
  • –Copeptin
  • –Galectin 3
  • –MMP 9
  • –Occludin
  • –Total Tau
  • –S100

Question 223

How do you score the mini cog test

Answer 223

• 5 points total
  
  • Draw clock (2 points)
  • 3 objects recall (3 points)

Question 224

Identify the type of dementia

• Most common type
• Patient is 75 year old. —Showed up last week by mistake.

—Admits her memory is not as great as it used to be but not too bad. —Drives and lives alone since her husband died 5 years ago. —Has a son who lives in Cincinnati.

• —Mini cog 1/3 objects, clock –see picture. Mini cog is 1

**What is the disease? what are they symptoms (initial vs later), risk factors? treatment?

Answer 224

Alzheimer’s Disease

• –Memory loss
  
  • –Short Term memory- gradual onset
  • –Affects ability to function (if not = Mild Cognitive Impairment)
  • –Not explained by delirium or psych
• Symptoms besides short term memory loss
  
  • —Language -Word finding
  • —Visual images and spatial relationships
  • —Executive -Planning, solving problems, judgement
  • —Personality changes
• Later symptoms
  
  • —Unable to communicate
  • —Incontinence
  • —Unable to feed or dress themselves
  • —Fail to recognize family
  • —Unable to walk
• Risk factors
  
  • Age
  • Family history; –10 to 30% higher risk of developing AD if a first degree relative has the disease (parent, sibling, child). –The younger the person with the disease the higher the risk for relatives
  • Anything bad for the heart is bad for brain. so risk factors for heart disease are risk factors for Alzheimer’s; HTN, diabetes, Hypercholesteolemia, smoking.
• Genetic risk for alzheimer’s
  
  • Genetic mutaton (less than 5% of cases). Amyloid Precursor rotein. Presenilin1or Presenilin 2– Early onset - before 65. Autosomal Dominant
  • —APOE gene e4 –Late onset. one copy 3 X risk. two copies 8-12 X risk. not all people with this gene will get AD and not all people with AD have this gene.
• Morphology
  
  • Plaques and tangles
• Predictable decline in alzheimer
  • —Preclinical AD 20 yrs - biomarkers
  • —Mild Cognitive Impairment 5 years
  • —Symptomatic AD 10 years
  • —Death
• Treatment; does not affectt the course of the disease
  
  • –acetylcholinesterase inhibitors
  • –N methyl D aspartate receptor inhibitor- glutamate pathway

Question 225

Identify type of dementia

• –Often occurs along with AD (mixed pattern)
• –Step-wise progression
• –Risk factors for vascular disease (e.g stroke)
• –Diagnosed with CT scan

Answer 225

Vascular type Dementia

Question 227

type of dementia

• –Has symptoms of both dementia and Parkinson’s Disease
• –Visual hallucinations and falls
  
  • see children in the room that are not there
  • loss motor function early so the falls

Answer 227

Lewy Body Dementia

Question 228

Type of dementia

• rare
• Younger
• Emotional
• Language
• Compulsive
  
  • eat alot

Answer 228

Picks Disease

• Pick’s or frontotemporal type

Question 229

Identify condition

• —Too much fluid around the brain
• —May be reversible with shunt
• —Diagnosed with CT or MRI
• —Wacky, Wet, and Wobbly
  
  • Incontinence, memory loss, unsteady gait

Answer 229

Normal Pressure Hydrocephalus

Question 230

Identify neurocognitive disordes caused by the follwoing

• Infections
• Deficiency
• chronic alcohol abuse

**Identify suggested evaluation and test

Answer 230

• ◦Infections
  
  • –HIV
  • –Syphilis
  • –Creutzfeldt-Jakob -prion
• ◦Deficiencies
  
  • –B12 deficiency
  • –Hypothyroidism
• ◦Chronic alcohol abuse
  
  • –Korsakoff’s syndrome-thiamine

—Suggested Evaluation

• ◦Thorough history and physical examination and cognitive testing

Cognitive tests

• —MOCA Montreal Cognitive Assessment

◦Lab studies:

• –Minimum - CBC, CCP, B12, TSH

◦Imaging:

• –Head CT without contrast
• –Usually DON’T do – PET

◦Research or special interest only:

• –Biomarkers
• –Genetic testing

◦Brain biopsy could make definitive diagnosis but DON’T DO THIS ◦We “rule out” other diagnoses.

Question 231

Work up for neurocognitive disorder (dementia)

Answer 231

• —Suggested Evaluation
  
  • ◦Thorough history and physical examination and cognitive testing
• Cognitive tests
  
  • —MOCA Montreal Cognitive Assessment
• ◦Lab studies:
  
  • –Minimum - CBC, CCP, B12, TSH
• ◦Imaging:
  
  • –Head CT without contrast
  • –Usually DON’T do – PET
• ◦Research or special interest only:
  
  • –Biomarkers
  • –Genetic testing
• ◦Brain biopsy could make definitive diagnosis but DON’T DO THIS ◦We “rule out” other diagnoses.

Question 232

Explain the MOCA test

• score (normal levels)

Answer 232

MOCA test

• Visuospatial/executive
• Naming
• Memory
• Attention
• Language
• Abstraction
• Delayed recall
• Orientation - OPTIONAL

Score

• Normal levels is >=26/30
• Add 1 point if <= 12 yr education

Question 233

69 y.o male

• —previously alert and oriented with no psych history
• —s/p repair of aortic aneurysm.
• —post op day 2
• —he pulled out his IV and is trying to get out of bed
• —agitated and not paying attention to your questions. He says he wants to go home.
• —On physical exam, T 99, BP 150/90, pulse 100, RR 18 Oxygen sat 95%
• —Agitated and uncooperative
• —HEENT normal, Lungs clear, CV RRR
• —Abd wound looks good, normal bowel sounds
• —EXT no edema
• —Foley catheter in place
• —Neuro moving all extremities, reflexes equal

Answer 233

Delirium; DSM- definition

• —Inattention
• —Acute onset or fluctuating course
• —Disorientation
• —Not caused by a pre-existing problem
• —Evidence of an acute medical condition causing it

Question 234

How do you diagnose delirium?

Answer 234

Delirium- Diagnosis by Confusion Assessment Method (CAM)

—Dx requires features 1 and 2, and 3 or 4

• —1 - Acute onset and fluctuating course AND
• —2 – Inattention

AND either

• —3 - Disorganized thinking OR
• —4 - Altered level of consciousness

Risk factors

• —Functional impairment
• —Lack of physical activity
• —Alcohol abuse
• —Vision problems
• —Hearing loss

Question 235

Causes of Delirium

Answer 235

D.E.L.I.R.I.U.M

• Drugs, Drugs Drugs!!
• Electrolyte/endocrine disturbances (dehydration, sodium imbalance, uremia, hypercalcemia, hypoglycemia, thyrotoxicosis)
• Lack of drugs (withdrawal from ETOH, benzos or poor pain control, B12 deficiency)
• Infection (urinary tract, pneumonia, sepsis, meningitis, encephalitis)
• Reduced sensory input (can’t see or can’t hear)
• Intracranial (infection, hemorrhage, stroke, tumor)
• Urinary, fecal (urinary retention, fecal impaction)
• Major organ system issues– infarction, arrhythmia, shock, COPD, hypoxia, hypercapnia, renal failure, liver failure, hypertensive encephalopathy

**Blood loss from surgery - orthopaedic surgery (post op day 1 or 2), AAA repair, thoracic surgery

Question 236

Prevention and treatment strategies

Answer 236

Prevention

• —Reorient -whiteboard
• —Minimize sleep deprivation
• —Walk
• —Water
• —Oxygen
• —Food
• —Treat pain
• —Prevent constipation
• —Hearing aids
• —Glasses
• —No restraints
• —No catheters

Treatment

• —Treat the cause and get rid of precipitants
• —Supportive – call in family
• –For severe agitation only:
  
  • –Safety risk to self or others
  • –Risk of interrupting needed care, e.g. attempting self-extubation or pulling out IV
• Pharmacology treatment
  
  • –First line: haloperidol
  • –Alternate 1st line: Atypical antipsychotics – risperidone, olanzapine, quetiapine

Question 237

How do you distinguish between delirium and dementia

• similarities
• differences

Answer 237

—Features seen in both:

• ◦Disorientation
• ◦Memory impairment
• ◦Paranoia
• ◦Hallucinations
• ◦Emotional lability
• ◦Sleep-wake cycle reversal

—Key features of delirium and not dementia:

• ◦Acute onset
• ◦Altered level of consciousness

Question 238

Summary of delirium

• ◦Delirium is acute or fluctuating change in mental status with inattention and change in level of consciousness
• ◦Think of reversible causes like infection, pain, constipation, etc.
• ◦Prevention – less tubes, restraints, and drugs
• ◦Treatment- drugs are last resort/temporary

Question 239

Brain tumors

• Epidemiology
• Unique Characteristics
• Clinical presentation
• Diagnosis
• unequivocal risk factor

Answer 239

Brain tumors

Epidemiology

• •10-17 cases per 100,000 people
• •50-75% primary tumors
• •25-50% metastatic tumors
• •Children:
  
  • •Cancer is #2 cause of death
  • •Of cancers: #1 Brain tumors (20%), #2 Leukemia
  • •70% in posterior fossa
• •Adults: 70% supratentorial

Unique Characteristics

• •More difficult to tell benign from malignant
• •Difficult to completely resect glial tumors
• •Anatomic location can have serious and even lethal consequences regardless of benign or malignant
• •Rarely get mets outside CNS, can seed along spinal cord causing meningitis

Clinical presentation

• •Generalized: ↑ ICP – HA, NV, CN-3 or CN-6 palsy
• •PE: fundoscopic exam - papilledema
• •Focal: hemiparesis, aphasia, seizures
• •Tumors in ventricles present with hydrocephalus

Diagnosis

• •Diagnosis: MRI with contrast
• •Blood-brain barrier prevents contrast from entering healthy brain
• •Leaky new vessels in tumor allow contrast to enter, known as contrast-enhancing lesion

Only unequivocal risk factor

• •Ionizing radiation

Question 240

Identify brain tumor

• •Used to think these tumors were derived from their specific mature cell types in the CNS (astrocyte → astrocytoma, oligodendrocyte → oligodendroglioma, ependymal cells → ependymoma)
• •Now, the tumors are thought to originate from progenitor cells that preferentially differentiate down one of the cellular lineages

Answer 240

GLIOMAS

Question 241

Brain tumors

• •WHO histologic grading for astrocytomas (4)
• 2 categories of astrocytoma

Answer 241

•I-IV

• • I: well-differentiated – pilocytic astrocytoma
• • II: diffuse growth of well-differentiated astrocytes – diffuse or fibrillary astrocytoma
• •III: anaplastic features (pleomorphism increased mitoses) – anaplastic astrocytoma
• •IV: undifferentiated w/vascular proliferation an necrosis – glioblastoma

Astrocytoma - 2 categories

• •Infiltrating and Noninfiltrating

Question 242

Describe infiltrating astrocytoma

Answer 242

Astrocytoma - Infiltrating

• •~80% of primary brain tumors
• •Range from well-differentiated (low grade) to undifferentiated (high grade)
• •Some tumors progress from low grade to glioblastoma due to accumulation of mutations
• •Most common mutations affect p53 and PDGF

_**Infiltrating astrocytoma are harder to resect. A lower grade (esp Grade II which occur in younger people) can come back later to become a higher grade (esp Grade IV in older people)_

Question 243

Identify type of infiltrating astrocytoma

• •Occur in younger adults
• •Present with seizure, HA, focal neurologic deficits
• •Histology: increase in number of glial cells, variable nuclear pleomorphism, GFAP-positive astrocytic processes give a fibrillary background

Answer 243

•Fibrillary/Diffuse astrocytoma (II/IV)

• •Transition between neoplastic and normal tissue is indistinct, tumor cell processes infiltrate normal tissues
• •Median survival: 5 years
• •May recur as high grade tumor

Question 244

Identify type of infiltrating astrocytoma

• •Regions of more densely cellular with greater nuclear pleomorphism, mitotic figures

Answer 244

•Anaplastic astrocytoma (III/IV)

• •Diagnosis: of diffuse and anaplastic:
  
  • •MRI: non-enhancing lesion, may not be seen on CT, brain biopsy
• •Treatment: Surgical resection, but often cannot be resected due to size and location. Radiation - most effective nonsurgical treatment
• •Median survival: ~2 yrs, most tumors progress to high-grade

Question 245

Identify type of infiltrating astrocytoma

• •High-grade end of spectrum of astrocytomas, most atypical & mitotically active
• •Primary
  
  • •Most common type
  • •New onset disease in older people
• •Secondary
  
  • •Younger patients
  • •Due to progression of a lower grade astrocytoma (see above)

Answer 245

•Glioblastoma (IV/IV)

• ​•Four molecular subtypes: (common theme – most affect two cancer hallmarks: sustained proliferative signaling and evasion of growth suppressors)

Question 246

Identify example of grade IV infiltrating astrocytoma

• **Subtypes

Answer 246

Infiltrating Astrocytoma Grade IV - GLIOBLASTOMA

Subtypes

Classic

• •Accounts for majority of primary glioblastomas
• •Genetics
  
  • •Mutations in PTEN tumor suppressor gene
  • •Deletions of chromosome 10

•Proneural

• •Most common type associated with secondary glioblastoma
• •Genetics
  
  • •Mutations in TP53
  • •Point mutations in IDH1, IDH2

•Neural

•Mesenchymal – deletions or lower expression of NF1 on chromosome 17

Question 247

Identify brain tumor

Answer 247

Glioblastoma (IV/IV)

• Shows increased cellularity, pleomorphism, and mitotic figures

Question 248

identify brain tumor type ***Be specific

• •Children and young adults
• •Relatively benign behavior
• •Location: 1. Cerebellum, 2. Third ventricle
• •Often cystic with mural nodule in wall of cyst
• •Histology: cells with hair-like processes, Rosenthal (eosinophilic) fibers
• •Grow very slowly, recurrence often involves cyst enlargement rather than growth of solid component
• •Pts have survived >40 years past incomplete excision

Answer 248

Non-Infiltrating Astrocytoma

• •Pilocytic Astrocytoma (I/IV)

Question 249

identify brain tumor type

• •Adults, 4th and 5th decades
• •Slow growing, may be diagnosed after years of neurologic complaints
• •Most often in cerebral hemispheres
• •Histology: sheets of regular cells with spherical nuclei, surrounded by clear halo of cytoplasm (poached egg appearance) - see picture
• •Calcifications – 90% of oligodendrogliomas

Answer 249

•Oligodendroglioma II/IV, III/IV (anaplastic)

• •Genetics:
  
  • •Mutations in IDH1 and IDH2 (90% of tumors)
  • •Co-deletions in chromosome 1p and 19q (80% of tumors)
• •Rx: surgery, radiation & chemotherapy
• •Median long term survival: 5-10 yrs, in general prognosis is better than astrocytoma
• •Higher grade oligodendrogliomas (anaplastic oligodendrogliomas III/IV) have a poorer prognosis

Question 251

Identify type of brain tumor

• •Most often a tumor of children and young adults
• •Occur most often in ependymal-lined ventricular system
• •Children and young adults: Fourth ventricle
• •Adults: Spinal cord
• •Present with hydrocephalus, get CSF dissemination

**PICTURE SHOWS - perivascular pseudorosettes

• •Histology: small dark cells, variably dense fibrillary background between nuclei, form perivascular pseudorosettes, benign appearing

**Identify prognosis and subtype

Answer 251

•Ependymoma II/IV and III/IV (anaplastic)

• •Prognosis: posterior fossa lesions ~5 years after surgery; resected supratentorial and spinal cord lesions have a better prognosis
• •Subtypes:
  
  • •Myxopapillary ependymoma (I/IV) – occurs in filum terminale. May extend into subarachnoid space and surround roots of cauda equina, difficult to resect, recurrence likely

Question 252

Identify brain tumor

• •Most common in children, in lateral ventricle
• •Adults, in fourth ventricle
• •Papillary growth with connective tissue stalk
• •Microscopically look just like normal choroid plexus
• •Present with hydrocephalus

Answer 252

Choroid Plexus Papillomas

Question 253

Identify brain tumor

• •Young adults
• •Attached to roof of the ventricle
• •Can obstruct the foramina of Monro
• •Can cause hydrocephalus
• •Can be rapidly fatal
• •Clinical: may complain of positional headache

Answer 253

•Colloid cyst of third ventricle

Question 254

Identify brain tumor

• •WHO Grade IV/IV
• •Highly malignant tumor of children
• •Cerebellum only, midline
• •Rapid growth may result in hydrocephalus
• •Histology: Small round blue cell tumor, rosettes or perivascular pseudorosettes

Answer 254

Embryonal Tumors OR Primitive Neuroectodermal Tumors (PNET)

• Medulloblastoma
• •Dissemination through CSF, ‘drop’ metastasis when it spreads down the spine even to cauda equina
• •Radiosensitive
• •5 year survival: 75% with complete excision and RT

Question 255

Identify subtypes of medulloblastoma (4 groups)

Answer 255

• WNT type
  
  • best prognosis
• SHH type
• Group 3
  
  • worst prognosis
• Group 4

Question 256

Identify brain tumor

• •Children
• •Cerebral hemispheres
• •Resemble medulloblastoma in histology and poor degree of differentiation but differ in location
• •Genetically distinct from medulloblastoma

Answer 256

•CNS supratentorial primitive neuroectodermal tumors (CNS PNET)

Question 257

Identify brain tumors

• •Comprises 1% or less of all primary brain tumors
• •Most common CNS neoplasm in immunosuppressed patients (think AIDS)
• •Incidence has tripled in past two decades
• •Patients get multiple tumor masses within the brain but rarely spreads to lymph nodes or outside the brain

Answer 257

Primary Brain Lymphoma

• •If patient has non-CNS lymphoma rarely involves brain parenchyma – although can spread to CSF
• •Majority CNS are B cell lymphomas, containing EBV genes
  
  • •In immunosuppressed, contain EBV genes
  • •If not associated with immunosuppression, then phenotype is typical of postgerminal center B cell differentiation
• •Aggressive disease, no role for resection, does not respond as well to chemotherapy
• •Median survival – 4-5 years

Question 258

Brain tumors

• Identify types of the tumors

Answer 258

•Metastatic Tumors

• •Most common sites: Lung, Breast, Skin (melanoma), Kidney, & GI tract
  
  • (Lots of Bad Stuff Kills Glia)
• •Usually occur as multiple masses
• •Treatment may improve quality of remaining life

Question 259

Identify type of brain tumors

• •Most are WHO Grade I/IV, overwhelming majority are benign, few are III or IV/IV
• •Actually not true brain tumors; arise from meningothelial cells that form external membranes covering the brain
• •Constitute 20% of intracranial tumors
• •Majority are found in adults as asymptomatic tumors discovered incidentally at autopsy

Answer 259

Meningioma

• •Can present as a headache or with neurologic sx
• •Multiple meningiomas are found in patients with neurofibromatosis type 2 (NF2)
• •Dural based tumor
• •Common sites:
  
  • •Parasagittal aspect of the brain convexity
  • •Dura over the lateral convexity
  • •Wing of the sphenoid
  • •Olfactory groove
  • •Sella turcica
  • •Foramen magnum

Question 260

What do you see on MRI vs histology with meningioma

Answer 260

• •MRI
  
  • •See adjacent to bone & have “dural tail” which indicates tumor is anchored to the dura
  • •Contrast-enhancing lesion
• •Histology – there are many growth patterns
  
  • •Syncytial – Whorls of bland cells
  • •Psammomatous – Psammoma bodies
• If occurs as small lesion, can just be followed
• Surgery is definitive therapy, although even with complete resection, 20% recur
• Prior RT is a risk factor

Question 261

Identify type of brain tumors

• •Usually suprasellar arising in pituitary stalk
• •Arise from remnants of Rathke’s pouch
• •Bimodal distribution: Ages 5 – 14 yrs and
• > 65 yrs
• •5 – 10% of brain tumors in children
• •Slow growing, benign, malignant transformation to squamous cell cancer is very rare
• •Solid or mixed solid and cystic

***2 histologic types??

Answer 261

•Craniopharyngioma

•Two histologic types:

•Adamantinomatous

• •Children
• •Stratified squamous epithelium in nests or chords
• •Spongy reticulum
• •Calcifications
• •Lamellar keratin formation
• •Cysts with thick brownish-yellow fluid contents

•Papillary

• •Adults
• •Solid sheets and papillae lined by squamous epithelium
• •No keratin, calcifications or cysts

Question 262

Brain tumor - craniopharyngioma

• Clinical
• Treatment

Answer 262

•Clinical

• •Visual symptoms from pressure on optic chiasm
• •Children: growth retardation 2° pituitary hypofunction and GH deficiency
• •Headache

•Treatment – surgery and/or radiation therapy

Question 263

• •Often arise directly from peripheral nerves, attach to but do not invade the nerve
• •Commonly seen at cerebellopontine angle where attached to vestibular branch of 8th cranial nerve – also called acoustic neuroma
• •Patients present with tinnitus and hearing loss
• •Outside of the dura they are commonly found associated with large nerves
• •Associated with neurofibromatosis type 2 (NF2)

Answer 263

Schwannoma

• •Appear as well-circumscribed, encapsulated mass attached to nerve, but can be separated from the nerve
• •Shows mixture of 2 growth patterns
  
  • •Antoni A: moderate to high cellularity with nuclear palisading; “nuclear-free zones” called Verocay bodies
  • •Antoni B: less cellular area, more myxoid
• •Completely benign lesion – surgical removal is curative

Question 264

Identify example of peripheral nerve sheath tumors

Answer 264

Neurofibromas

• Benign spindle cell lesions which occur in three forms
• Superficial cutaneous
• •Occur in skin or peripheral nerve
• •Sporadic or associated with NF1
• •Never turn malignant
• Diffuse: Large plaque-like elevation of skin, NF1-associated
• Plexiform – only occur in patients with NF
• •Significant potential for malignant transformation
• •Occurs associated with large nerves, cannot be separated from the nerve

HISTOLOGY; Admixed

• •Neoplastic Schwann cells
• •Perineurial-like cells
• •CD34+ spindle cells
• •Fibroblasts

Question 265

Identify Familial tumor syndromes

• • Features
  
  • •AD
  • •Get multiple neurofibromas: superficial cutaneous, diffuse & plexiform
  • •Get gliomas of optic nerve
  • •Pigmented nodules of iris (Lisch nodules)
  • •Café au lait spots – brown spots on skin
• •Genetics: NF1 gene neurofibromin, tumor suppressor gene, chromosome 17

Answer 265

•Neurofibromatosis – NF1

• •One of the more common genetic disorders
• •Increased propensity for neurofibromas to undergo malignant transformation

Question 266

Identify familial tumor syndromes

•Features

• •AD
• •Develop range of tumors: bilateral acoustic neuromas, multiple meningiomas, ependymomas of spinal cord
• •Much less common than NF1

•Genetics: different gene involved, NF2 gene merlin, chromosome 22

Answer 266

•Neurofibromatosis – NF2

Question 267

Identify familial tumor syndromes

• •AD, but 70% occur as spontaneous mutation
• •Develop hamartomas & benign neoplasms involving brain & other tissues
• •Within CNS, hamartomas occur as “cortical tubers” – abnormal, broad, firm gyri (potato-like)
• •CNS hamartomas – occur as haphazardly arranged neurons which lack normal neural organization

Answer 267

Familial tumor syndrome

•Tuberous sclerosis

• •Extracranial lesions: renal angiomyolipomas, pulmonary lymphangiomyomatosis & cardiac myomas, skin rash (angiofibromas)
• •Can have seizures, mental retardation – tumors are epileptogenic
• •Treatment – symptomatic

Question 268

Identify familila tumor syndromes

• •AD
• •Develop capillary hemangioblastomas in cerebellum, retina, & spinal cord
  
  • •Highly vascular tumor which can occur as mural nodule associated with fluid-filled cyst
  • •Patients can have associated polycythemias in 10% of cases (tumor produces erythropoietin)

Answer 268

•von-Hippel-Lindau

• •Also can have cysts in pancreas, liver & kidney
• •Increased risk of renal cell carcinoma and pheochromocytoma
• •Gene is tumor suppressor