NBB (Neuron, Brain, Behavior) 1

Question 1

Explain the concept of localization of function

Answer 1

Specific brain regions have specific functions –> by testing different functions, testing different parts of the brain
can use MRI to visualize neural localization

Question 2

Define and describe neuroplasticity

List the types of cellular changes that underlie neuroplasticity

Answer 2

Neuroplasticity - potential that the brain has to reorganize to adapt to the environment –> changes in neurons and pathways in response to experience –> regions can take over for others that have been damaged e.g. prosthetics, implants, making new associations

Cellular changes: axon sprouting, dendritic branching synaptogenesis (creating new dendritic spines), neurogenesis, angiogenesis

white matter (axon) plasticity can include myelin formation or remodeling, fiber organization, astrocyte changes, angiogenesis

Question 3

Explain the difference between a focal and a diffuse lesion

Answer 3

Focal lesion - infection, tumor, or injury that develops at restricted or circumscribed area of neural tissue –> produces focal neurological signs that can be traced to part of the brain eg loss of pain on half the face, loss of vision in one eye

Diffuse lesion - general, such as neurodegenerative diseases, psychiatric disorders, infections, malnutrition, genetic disorders, compression –> diagnosis depends on the beginning symptoms, patterns, and time course

episodic --> migraine, seizures
relapsing, remitting --> MS
sudden onset, lasting deficits --> Stroke
slow, progressive --> PD, Alzheimer's
fast, progressive --> tumor, pressure

Question 4

Describe the morphological classification of neurons and where they are found

1) Pseudounipolar
2) Bipolar
3) Multipolar

Answer 4

1) Pseudounipolar - sensory PNS neuron; cell body migrated out, axon split into two branches - one to spinal cord (CNS) and one to periphery
2) Bipolar - two axons from the cell body; specialized sensory PNS neurons for eyes (sight), ears (hearing), nose (smell)
3) Multipolar - single long axon and multiple dendrites; found in CNS and PNS; most common

Question 5

Describe general structure of neurons.

PNS: Describe types of neurons and morphological classification

1) Afferents
2) Efferents

CNS: Describe types of neurons:

1) Interneurons
2) Local neurons
3) Projection neurons

Answer 5

Neuron: dendrite (receives input), cell body, axon (sends output via action potentials)

PNS:

(1) Afferents - carry sensory information from periphery –> CNS; usually pseudounipolar
(2) Efferents - CNS –> motor signals to efferent motor neurons whose axons terminate on organs/muscle; multipolar

CNS:

1) Interneurons - ANY neurons that form connections in CNS –> process and integrate info; multipolar
2) Local neurons - connect to cells in immediate region
3) Projection neurons - project to more distant areas of CNS in tracts

Question 6

Differentiate between the following:

1) CNS convergence vs divergence pathways
2) decussation vs commissure
3) clusters of nuclei vs axons
4) white matter vs gray matter

Answer 6

1A) CNS divergence - multiple outputs from axon terminals via axon collaterals (branches) –> can send info to several pathways/parts of nervous system
B) CNS convergence - multiple inputs to a neuron –> integration of inhibitory and excitatory information eg motor, sensory systems and associative learning

2A) decussation - pathway crosses midline
B) commissure - white matter (Axon) tract that connects structures on the R and L sides of the CNS

3A) cluster of nuclei –> nucleus (CNS), ganglia (PNS)
B) clusters of axons –> tract, nerve, funiculus

4A) White matter - axons
B) gray matter - nuclei/cell bodies and synapses

Question 7

What are glial cells? 
Describe the different types and where they are found
1) Astrocytes
2) Oligodendrocytes
3) Microglia 
4) Satellite cells
5) Schwann cells

Answer 7

Glial cells - guide neurons, build myelin sheaths, buffer from ions

1) Astrocytes [CNS]- macroglia; physical support, component of blood-brain barrier, K+ metabolism, remove excess neurotransmitter, produce neurtrophic factors and scar tissue post injury, form glial membrane ( called external limiting membrane)
2) Oligodendrocytes [CNS] - macroglia; myelinate multiple axons
3) Microglia [CNS] - phagocytic scavenger cell activated post tissue damage (injury, infection, disease) –> produces growth factors
4) Satellite cells [PNS] - macroglia; provides nutrients and structural support for neurons iN PNS
5) Schwann cells [PNS] - macroglia; myelinate only one axon in PNS

Question 8

What is the resting membrane potential (RMP)? What are the relative concentrations of 
Na+
Cl-
Ca2+
K+

Answer 8

Resting membrane potential - charge across neuron membrane; usually -65 mV because of osmotic/electrical forces, permeability of neuron, and Na+/K+ pump

Na+, Cl-, and Ca2+ all have higher concentrations OUT&raquo_space; IN

K+ and organic anions have higher concentrations IN&raquo_space; OUT

Question 9

What are graded membrane potentials?

Answer 9

Graded potentials - changes to resting membrane potential in response to inputs; magnitude varies based on strength of input; arise from summation of individual gated ion channels
A. hyperpolarizing - negative, inhibitory
B. depolarizing - positive, excitatory

Question 10

Describe the difference between EPSPs and IPSPs

Answer 10

EPSPs = Excitatory Post-synaptic potentials –> depolarizing, graded
usually arise from opening of Na+ or Ca2+ (influx) channels –> make RMP more positive and more likely to have action potential

IPSPs = Inhibitory Post-synaptic potentials –> hyperpolarizing, graded
usually arise from opening of Cl- (influx) or K+ (efflux) channels –> make RMP more negative

whether neurotransmitter evokes EPSP or IPSP depends on the post-synaptic receptor it binds to

Question 11

Describe importance of temporal and spatial summation with graded membrane potentials

Answer 11

Normally, graded potentials attenuate rapidly with distance
Temporal summation - inputs are in rapid succession so they build on each other
Spatial summation - multiple inputs simultaneously

Question 12

Describe the molecular processes that underlie action potentials

Describe propagation of action potentials

Answer 12

1) Action potentials occur when membrane potential hits the threshold –> “Trigger zone” usually with lot of Na+ channels

Na+ channels open and Na+ rushes into the cell and depolarizes it –> K+ channels open after (slower) so both channels are open; K+ leaves the cell and makes RMP more negative –> Na+ channel closes while K+ is still open (Refractory period) –> both Na+ and K+ are closed

2) Propagation: local depolarization causes current to flow in both directions –> neighboring voltage gated Na+ channels opens –> continuous repeated process but only in one direction along the axon bc the prior sections are refractory

Question 13

Explain the function of myelin and axon diameter on conduction velocity

Answer 13

Conduction velocity of action potential increases with:

1) myelination (insulated area with no voltage gated channel underneath) - bc action potential jumps from nodes of ranvier
2) increased axon diameter - bc larger internodal spaces and increased space constants (current can move along further before it attenuates)

Question 14

Describe 2 diseases related to demyelination

Answer 14

1. Multiple Sclerosis - autoimmune inflammatory disorder; demyelination of oligodendrocytes
2. Guillan-Barre - viral infection leads to inflammation-induced demyelination of peripheral nerves –> Ascending weakness and elevated protein in CSF

Question 15

List the steps of synaptic transmission

Answer 15

1. Transmitter synthesized and stored in synaptic vesicles
2. action potential reaches presynaptic terminal
3. depolarization of presynaptic terminal –> opening of voltage gated Ca2+ channels
4. Ca2+ influx
5. Ca2+ causes vesicles to fuse with presynaptic membrane
6. Transmitter released into synaptic cleft
7. Transmitter binds to receptor molecules in postsynaptic membrane
8. opening/closing of postsynaptic channels
9. postsynaptic current causes postsynaptic potential –> changes excitability of postsynaptic cell
10. removal of neurotransmitter by glial uptake or enzyme degradation
11. retrieval of vesicular membrane from the plasma membrane

Question 16

Describe the 2 families of postsynaptic receptors:

1. Ionotropic
2. Metabotropic

Answer 16

1. Ionotropic - receptor is linked directly to ion channels - neurotransmitter binds to receptor –> conformational change allows ion flux; v fast
2. Metabotropic - receptor does not have a channel - neurotransmitter binds –> G protein messengers released –> causes conformational changes in channel and ion flux; slower, allows for neuromodulation

Question 17

List the major neurotransmitters that act at ionotropic receptors:

1. Excitatory [PNS]
2. Excitatory [CNS]
3. Inhibitory [CNS]
   * NO inhibition in PNS

Answer 17

1. Excitatory [PNS] = Acetylcholine
2. Excitatory [CNS] = Glutamate –> in ~50% of all neurons; can act at metabotropic (excitatory or inhibitory) or ionotropic (exclusively excitatory) post-synaptic receptors
3. Inhibitory [CNS] = GABA or glycine –> opens ligand-gated Cl- channels

Question 18

Discuss the characteristics and significance of the NMDA receptor.

Answer 18

NMDA - N-methyl-D-aspartate ionotropic receptor

• BOTH voltage gated and ligand-gated channel –> needs both depolarization and glutamate
• at RMP - receptor channel is blocked by Mg2+
• at depolarization - glutamate binds + Mg2+ displaced –> Ca2+ influx

Unique characteristics:

• intracellular signals (kicked off by Ca2+ influx) –> long-term synaptic changes –> regulating neural circuits, learning and memory, changes in dendritic spines, insertion of AMPA receptors
• receptor inhibited by hallucinogenic drugs –> produces hallucinations

long-term potentiation - increased responsiveness of post-synaptic neurons after repeated stimulation

Question 19

Describe glutamate toxicity

Answer 19

Trauma, diseases –> increased glutamate release/decreased uptake –> glutamate NMDA receptors activated –> Ca2+ influx into cells –> increased Ca2+ causes increased water uptake and stimulation of enzymes –> neurons self-digest

associated with ALS, Alzheimer’s tumors, ischemia, trauma, seizures

Question 20

Describe the projection origin and functions of the major neuromodulators in the brain:

1. Norepi
2. Dopamine
3. Ach
4. Endogenous opioids
5. Unconventional neurotransmitters

Answer 20

Neuromodulators - affect neuronal excitability

1. Norepi - originates in locus ceruleus (pons); stress hormone, stimulated by amphetamines and Ritalin
2. Dopamine - originates in ventral tegmentum and substantia nigra (midbrain); functions in control of movement, reward pathway, and working memory via different pathways (increased in Huntington but decreased in Parkinson, depression)
3. Acetylcholine - originates in basal forebrain and pons; functions in arousal and memory (degenerates in Alzheimer’s, Huntington’s)
4. Endogenous opioids - originate in spinal cord, brainstem, and forebrain; functions in pain and reward
5. unconventional neurotransmitters (not stored) –> A. endocannabinoids (activated by THC) - lipid metabolites that decrease pain signals
   B. NO and CO - gases that are involved in neurodegenerative processes

Question 21

ID the sensory and motor regions of the spinal cord

Answer 21

Spinal cord: foramen magnum –> L1 vertebral body

Bell-Magendie Rule: dorsal (posterior) portion of spinal cord is sensory, ventral (anterior) is motor

Sensory inputs (afferents) from periphery and through dorsal root to the brain
Motor outputs (efferents) through ventral root out to periphery

Question 22

ID the 3 major areas of the brainstem and their functions/associated cranial nerves

Answer 22

Brainstem: transition between spinal cord and brain

1. Medulla - regulate body homeostasis and reflexes (vomiting, coughing, swallowing); cranial nerves IX, X, XI, XII (info from taste, skin of head/heart/lungs, digestive system)
2. Pons - balance, eye movements, facial expressions, reflexes (eyes, jaw); cranial nerves V, VI, VII, VIII
3. Midbrain - control orienting to sound, visual reflexes, motor control; source of dopamine projections to cortex for movement and habit formation; cranial nerves III and IV

Question 23

What is the reticular formation and where is it found? What is the reticular activating system

Answer 23

Reticular formation - network of nerve pathways (nuclei + neuronal circuits) that run through the core of the brainstem; mediate overall level of consciousness

nuclei are origins of projections to cortex or spinal cord e.g. rostral projections from the midbrain and pons form the reticular activating system –> project to cortex/through thalamus to control attention, arousal, sleep, wakefulness
caudal projections from pons and medulla –> control respiratory rhythms, bp, digestion, reflexes (yawn, swallow, vomit, gag)

Question 24

Describe the functions of

1) Cerebellum
2) Thalamus

Answer 24

1) Cerebellum - motor control, learning, posture, orientation, balance; damage causes ataxia
2) Thalamus - integrative center for inputs to the cortex eg sensory, motor, reticular formation, limbic; projections go to specific group of nuclei; thalamus is part of diencephalon

Question 25

List and describe the function of the 6 layers of cortex

Answer 25

1) Molecular - synaptic contacts from other layers
2) Small pyramidal - corticocortical connections
3) Medium pyramidal - corticocortical connections
4) Granular - inputs from thalamus (sensory)
5) Large pyramidal - outputs to CNS (motor)
6) Polymorphic - outputs to thalamus

Question 26

Explain the concept of somatotopy, retinotopy, and tonotopy in primary cortices

Answer 26

Primary cortices - topographically organized –> example of localization of function

Somatotropic arrangement - primary somatosensory and motor cortices
Retinotropic arrangement - primary visual cortex
Tonotopic - primary auditory cortex

Question 27

Explain the concept of somatotopy, retinotopy, and tonotopy in primary cortices

Answer 27

Primary cortices - topographically organized –> example of localization of function

Somatotropic arrangement - primary somatosensory and motor cortices
Retinotropic arrangement - primary visual cortex
Tonotopic - primary auditory cortex

Question 28

What is the function of CSF?

Describe flow of CSF beginning from the choroid plexus to the arachnoid villae

Answer 28

Functions: Protects the brain, maintains constant intracranial pressure, controls extracellular fluid

1. CSF produced in the choroid plexus within lateral ventricles
2. Flows through foramen of Munro (medially)
3. 3rd ventricle (sandwiched in the diencephalon)
4. Through the cerebral aqueduct of Sylvius (midbrain/ mesencephalon)
5. 4th ventricle (pons/medulla)
6. Exits through foramen of Luschka (2 lateral) and Magendie (1 medial)
7. Subarachnoid space around brain and spinal cord
8. Taken up into arachnoid villi/ granulations - evaginations of the the arachnoid membrane that allow CSF to drain
9. into the venous sinuses / system

Question 29

Describe the blood-brain barrier and the blood-CSF barrier

Answer 29

1. Blood-Brain barrier: Tight junction between astrocyte foot process and brain capillary endothelium

Protects brain from toxins/drugs, controls ionic environment, contains transporters; can break down quickly with trauma, infection

Circumventricular organs - regions where blood-brain barrier is interrupted

2. Blood-CSF barrier: Ependymal cells form tight functions = choroid epithelium –> blood-CSF barrier, need active transport to move across

However, the ependymal cells that line the ventricles have adhering junctions –> free movement of CSF into brain

Choroidal capillaries in ventricle (form from brain arteries in subarachnoid space) interact with the ependymal cells –> enable CSF to be produced

Question 30

Describe and identify the meningeal layers and spaces.

Describe differences between these layers in brain vs spinal cord

Answer 30

Pachymeninges –> (1) Dura - periosteal and meningeal
Leptomeninges –> (2) Arachnoid; (3) Pia

subarachnoid space is between pia and arachnoid - irregular space bc pia is against brain tissue but arachnoid is a covering –> creates cisterns

1. Dura: (brain) - 2 layers on top of each other; (spinal cord) dura mater separated from periosteum lining vertebral canal by epidural space
2. Arachnoid: (brain) arachnoid trabeculae and many cisterns; (spinal cord) fewer trabeculae and only one cistern
3. Pia: (spinal cord) forms denticulate ligaments which attach pia to arachnoid and dura

Question 31

Describe the clinical rationale for and functions of the lumbar puncture

Answer 31

Lumbar cistern / dural sac - between ending of spinal cord and ending of the dura / ending of vertebral column at coccyx

lumbar puncture done in this region - good place to sample CSF bc its all subarachnoid space + cauda equina

Where: done at L3/L4 in adults, further down in babies
Why: measure CSF pressure, obtain CSF sample to test for meningitis, Guillan Barre, MS (to confirm - not diagnostic), etc; administer chemo drugs
Why not: contraindicated if you know there is increased intracranial pressure (ICP) –> if you pull fluid out you will get a herniation

Question 32

ID The dural folds and describe the common areas of brain herniation

Answer 32

1. Dura - outermost meningeal membrane/layer
   Dural folds - inner dural layers between brain regions –> formed when dura goes into fissures; help support the brain

• Falx cerebri - forms right and left cerebral hemispheres
• Falx cerebelli - in between cerebellar hemispheres but much smaller
• Tentorium cerebelli - in between cerebellum and posterior cerebral hemispheres
• Diaphragm sellae - circular fold that covers sella turcica

2. Brain herniations - due to increased ICP (tumor, hematoma)
   A. Subfalcine - cingulate gyrus below falx cerebri
   B. Uncal - temporal lobe through tentorial notch
   C. Tonsillar - cerebellar tonsils through foramen magnum

Question 33

Describe the locations, causes, and symptoms of the following hematomas:

1) Subdural
2) Subarachnoid
3) Epidural

Answer 33

1) Subdural hematoma - in subdural space between dura and arachnoid (potential space)
A) Causes - due to rapid accelerations which tears bridging veins; seen more commonly in elderly
B) Symptoms - slower bleed and symptoms get worse with time; crescent shape on MRI

2) Subarachnoid - in subarachnoid space between arachnoid and pia (real space)
A) Causes - commonly traumatic but non-trauma includes ruptured aneurysm (most common type is Berry); can be venous or arterial blood and can be picked up in CSF
B) Symptoms - sudden-onset severe headache “worst in my life” from blood irritating meninges

3) Epidural hematoma - in epidural space between skull and dura (potential space)
A) Causes - usually due to trauma which tears middle meningeal artery (MMA); lens shape on MRI
B) Symptoms - brief period of lucidity before severe symptoms caused by brain herniation

Question 34

Define hydrocephalus and explain potential causes

What is the difference between communicating and non-communicating hydrocephali?

Answer 34

Hydrocephalus - “water in the brain” due to excess CSF

Potential causes:

1. Excess CSF production
2. Obstructed flow anywhere in ventricles or subarachnoid space (tumors, malformations, hemorrhage)
3. Decreased reabsorption through arachnoid granulations

Communicating - entire ventricular system clear through subarachnoid space e.g. problem with choroid plexus
Non-communicating - flow obstructed within ventricular system

Question 35

Describe Chiari Malformations and describe
Chiari I
Chiari II
Normal pressure hydrocephalus

Answer 35

Chiari malformations - congenital malformations of the cerebellum or brainstem –> result in downward displacement of cerebellar tonsils through foramen magnum into spinal canal

Symptoms usually in adults caused by compression of medulla and upper spinal cord, compression of cerebellum, and disruption of CSF flow through foramen magnum –> produces hydrocephalus

Chiari I - cerebellar tonsils below foramen magnum, seen in syringomyelia (anterior white commissure damage)–> headache, ataxia, impaired movement

Chiari II - less common but more significant herniation through foramen magnum –> meningomyecele (spina bigida), can cause aqueductal stenosis

Normal pressure hydrocephalus in the elderly - idiopathic, slow buildup–> gait disturbance, dementia, urinary incontinence NO headache “wet, wobbly, wacky”

Question 36

1. What is meningitis?
2. What is the difference between bacterial and aseptic meningitis?
3. What is the pathology of meningitis?

Answer 36

1. Meningitis - inflammation of the meninges; Meningitis can be acute, chronic or recurrent
2. Bacterial meningitis is septic and much more dangerous and life-threatening, aseptic meningitis is most common type, negative bacteriologic CSF –> can be viral or fungal or other
3. Pathology: prurulent exudate (pus) over spinal cord and brain; inflammatory changes (pleocytosis - abnormal cells) in CSF; spinal nerve/root inflammation; hydrocephalus; thrombosis of cerebral vessels –> ischemia and subarachnoid hemorrhage

Question 37

For bacterial meningitis:

1. Most common causes
2. Epidemiology
3. Lab diagnosis values
4. Treatment

Answer 37

1. Common causes: Strep pneumoniae (adults), Neisseria meningitidis (young adults), Group B beta-hemolytic Streptococcus GBS (babies)
2. Epi: Incidence higher in kids
3. Lab: cloudy appearance, increased pressure, chemistries (low glucose and high protein), gram stain (positive), high WBC
4. Treatment - antibiotics, steroids, supportive care

Question 38

Describe the pathogenesis of bacterial meningitis including devlpt of inflammatory response

Answer 38

Nasopharynx is the portal of entry - mucosal epithelium is attachment site for bacteria, which breeches host defenses

Most common pathogenesis is hematogenous spread, but also direct spread eg neighboring infections, cranial injury
Bacteremia - bacteria travels through blood to brain –> seeds meninges –> penetrates b/b barrier –> bacterial products/infection –> elicit cytokines to be produced –> activate WBCs, endothelial injury –> increased permeability of b/b barrier –> edema and increased intracranial pressure –> reduced cerebral blood flow –> brain ischemia and neuronal injury

Question 39

Describe the clinical presentation of bacterial meningitis

Answer 39

Clinical presentation: life-threatening emergency, occurs within hours to days (fulminant)

Symptoms: fever, nausea, Brudzinski sign (flex neck - knee pulls up), Kernig sign (cannot flex hip and knee), photophobia, headache (“worst headache of life” in adults, bulging soft spot in infants)

Cerebral edema and ischemia, thrombosis –> coma, ataxia, seizures, cranial nerve palsies

Clues: N. menigitidis - petechiae or purpura (bc it is vasculitis); S. pneumoniae - respiratory infections

Question 40

What are common acute complications of bacterial and aseptic meningitis

Answer 40

Bacterial - death, shock, seizures, SIADH, cerebral hemorrhage, cerebral infarct abcess

Sequelae - deafness, ataxia, hydrocephalus, develpt delay, paralysis, seizures, speech disorders

Aseptic - prognosis dependent on viral etiology, most patients recover fully without sequelae

Question 41

Identify the preventative measures employed in decreasing the incidence of both
bacterial and aseptic meningitis

Answer 41

Bacterial meningitis: Immunization and postexp prophylaxis (rifampin, ceftriaxone) for H. influenzae B, N. meningitidis
Only immunization for S. pneumoniae and nothing for gram-negative bacilli

Aseptic meningitis: Immunization (MMR) for mumps

Question 42

For aseptic meningitis:

1. Most common causes
2. Epidemiology
3. Lab diagnosis values
4. Treatment

Answer 42

1. Most common causes: enterovirus, herpes, arbovirus (insect vector)
2. Epidemiology: mucosal colonization –> escapes host defenses –> spreads hematogenously from blood to CNS –> invades CNS
3. Lab: spinal tap + CSF labs; clear appearance, normal glucose high protein

Question 43

Describe clinical presentation of aseptic meningitis

Answer 43

Not as sick as with bacterial meningitis - most cases mild and insidious, though herpes simplex virus can be fatal

Symptoms: URI, myalgia/arthralgia, rashes

Question 44

Describe the major types of cholinoreceptors: Nicotinic including MOA, location, subtypes

Answer 44

Acetylcholine - major transmitter in brain and ANS; receptors for acetylcholine (“cholinoceptors”) distributed throughout brain and ANS

Nicotinic - 5 subunit ionotropic ligand-gated ion channel with 2 acetylcholine binding sites

MOA: binding of ligand –> conformational changes in receptor –> directly opens the channel –> opening of Na+/K+ channels –> depolarization

A. Nn (neuronal type) - found in postganglionic cell bodies on autonomic ganglia, adrenal medulla
B. Nm (muscle type) - found in neuromuscular end plates of skeletal muscles

Question 45

Describe the major types of cholinoreceptors: Muscarinic including MOA, location, subtypes

Answer 45

Acetylcholine - major transmitter in brain and ANS; receptors for acetylcholine (“cholinoceptors”) distributed throughout brain and ANS

Muscarinic - 1 subunit transmembrane metabotropic G-protein coupled receptor

MOA: binding of ligand –> conformational changes in receptor –> activated G proteins recruit second messengers –> open separate ion channel

5 subtypes located in CNS, heart, smooth muscle, exocrine glands, sweat glands
A. M1 - CNS, sympathetic postganglionic –> 2nd messenger (Ca2+) opens channel
B. M2 - heart, smooth muscle –> dissociated G protein subunit opens channel
C. M3 - exocrine glands, smooth muscle –> 2nd messenger (Ca2+) opens channel
D. M4 - CNS –> dissociated G protein subunit opens channel
E. M5 - 2nd messenger (Ca2+) opens channel

Question 46

Describe the steps in synthesis, storage, release and termination of action of acetylcholine

Answer 46

1. Synthesis - cotransporter on cholinergic neuron has takes up choline –> Acetyl CoA + Choline –> Ach
2. Storage - ACh taken up by vesicles
3. Release - Ca2+ influx from calcium channel –> Triggers fusion of vesicle with plasma membrane –> Ach released into synapse –> taken up by cholinoreceptors on postsynaptic cell as well as autoreceptors (for feedback regulation)
4. Termination - acetylcholinesterase removes acetyl group –> choline + Acetate

Question 47

Distinguish between direct-acting cholinomimetics and indirect-acting agents

Answer 47

Indirect-acting cholinomimetic agent - do not mimic the acetylcholine directly but block the breakdown of endogenous neurotransmitter

Direct-acting cholinomimetic agents - cholinoceptor agonists e.g. bethanechol, pilocarpine that substitute for acetylcholine

Question 48

Describe the action of cholinesterase inhibitors:
A. Short-acting
B. Intermediate-acting
C. Long-acting

Answer 48

Acetylcholinesterase catalyzes ACh –> choline + acetate

A. Short-acting - reversible, bind weakly to actylcholinesterase enzyme, brief duration of action and rapid renal clearance e.g. edrophonium (myasthenia gravis MG)

B. Intermediate-acting - reversible and covalent binding; e.g. neostigmine, which resembles Ach but has serine residue instead of acetyl group –> due to stability of enzyme-inhibitor complex –> acetylcholinesterase unable to act on Ach
-can use for peripheral applications bc do not cross BBB

C. Long-acting - irreversible and covalent binding, not for therapeutic purposes (pesticides, organophosphates, chemical warfare agents e.g. sarin) - inactivate enzyme for hundreds of hours –> Cause cholinergic excess

Question 49

Major signs and treatment of cholinergic excess

Answer 49

Initial are signs of muscarinic excess, can be followed by CNS toxicity due to involvement of nicotinic receptors
D- diarrhea
U- urination
M- miosis (pupillary constriction)
B- bronchospasm
B- bradycardia
E- excitation of skeletal muscle + CNS
L- lacrimation
S- sweating
S- salivation 
Ultimately respiratory failure, paralysis, coma

Treatment - atropine (muscarinic antagonist) parenterally (IV) and benzodiazepines for seizures
-pralidoxime - chemical antagonist that interacts directly with and inhibits with organophosphate

Question 50

Describe the relationship between the spinal cord and vertebral column

When does the spinal cord end?

Answer 50

C1-C7 spinal nerves exit ABOVE corresponding vertebrae
C8 exits below C7, so C8-S5 exit BELOW corresponding vertebrae

Spinal cord ends at L1 at conus medullaris, from L1 to S2 is the cauda equina (spinal nerves) in the dural sac

so lumbar puncture is done L3-L5

Question 51

Explain the basic functions of each of the grey matter areas of the spinal cord

Answer 51

Grey matter is inside, white outside (opposite in the brain)

Dorsal horn - sensory processing, cell bodies of afferent sensory pseudounipolar neurons live in dorsal root ganglion and synapse in dorsal horn

Intermediate - sympathetic pre-ganglionic cell bodies in intermediolateral nucleus in lateral horns of T1-L3 (ONLY place there are lateral horns)
Parasympathetic pre-ganglionic cell bodies in interomediomedial nucleus of S2-S4

Ventral - motor neurons and interneurons, cell bodies of efferent lower alpha motor neurons (LMNs) in the ventral horn and go out through ventral root

Question 52

Distinguish between levels of the spinal cord in cross sections

Answer 52

From cervicomedullary junction –> cervical –> thoracic –> lumbar –> sacral direction:

• white matter decreases
• cervical is oval shaped, large dorsal and ventral horns
• thoracic is small, has lateral horns
• lumbosacral is round, large dorsal and ventral horns
• sacral - gray matter takes up a lot of space

Question 53

What is radiculopathy? What are the symptoms

Answer 53

Radiculopathy - damage to spinal nerve; most common pathology is herniated disc, also spinal stenosis, foraminal stenosis, osteophytes

Symptoms (follow nerve root pattern):
-burning, tingling pain that radiates from back along dermatome
-numbness (anesthesia = no sensation, analgesia = no pain)
-worsening with strain (cough, sneeze)
- muscle weakness
Above T1 –> Horner’s syndrome (constricted pupil “miosis”, inability to sweat normally “anhidrosis”, drooping eyelid “ptosis”)

Question 54

Describe the arteries of the spinal cord and the areas they supply

Answer 54

Anterior spinal artery - in ventral median fissure, supplies anterior 2/3 of spinal cord

Posterior spinal arteries (2) - in posterolateral sulci, supply posterior 1/3 of spinal cord

• vasocorona - series of connecting branches that form crown around the cord
• segmental arteries give rise to anterior and posterior radicular arteries at each spinal level –> supply dorsal/ventral roots and ganglia
• medullary arteries are at intermittent levels and merge with anterior/posterior spinal arteries
• Artery of Adamkiewicz is an anterior radicular artery at T9-L1, supplies lumbar and sacral spinal cord
• T4-T9 is watershed area

Question 55

Distinguish between symptoms related to spinal nerve injuries and spinal cord injuries

Answer 55

Spinal nerve injuries affect specific dermatomes - can trace back which nerves are injuried

Spinal cord injuries affect sensory levels –> due to spinal cord white matter tracts, injury leads to loss of function below level of lesion

Question 56

Explain the scoring for tendon reflexes and motor nerves. For each reflex test, name the spinal nerves that are tested

Answer 56

0+ = absent
1+ = trace
2+ = normal
3+ = brisk 
4+ = non-sustained clonus (muscle spasm)
5+ = sustained clonus 
*1,2,3 considered normal unless there is asymmetry 

Patella (knee jerk reflex)- L3-4
Biceps - C5-6
Brachioradialis - C5-6
Triceps - C7-8
Achilles - S1

Question 57

Describe the receptor, circuit and functions of the stretch reflex, golgi-tendon reflex and flexor withdrawal reflexes.

Answer 57

1. Stretch (deep tendon) reflex e.g. L3-L4 knee jerk reflex
   Stimulus - stretch
   Response - contraction
   Circuit: Muscle stretch receptor excited –> 1a afferent makes excitatory synapse onto one motor neuron (agonist muscle e.g. extensor) and excitatory synapse onto inhibitory interneuron (antagonist muscle e.g. flexor)
2. Golgi Tendon Organ (1b inhibitory reflex)
   Stimulus: muscle tension
   Circuit: Golgi tendon organ proprioceptors –> 1b afferent synapses onto 1b inhibitory interneurons –> inhibits agonist muscle (relaxes, lengthens) and excites antagonist muscle
3. Flexor withdrawal reflex: cutaneous nociceptor picks up pain –> Adelta afferent fiber synapses onto interneurons in spinal cord –> motor neurons activate flexor muscles on stimulated leg and stimulate extensor muscle on opposite leg (crossed-extension reflex)

Question 58

Describe role of proprioceptors in muscle action

Answer 58

Proprioceptors - provide information about body position/movement; intrafusal muscle fibers attached to/in parallel with skeletal muscle fibers –> increase muscle spindle fiber sensitivity

• 1a afferents that respond to rapid stretch, Group II for sustained stretch
• innervated by gamma motor neurons - activity increased during skilled movements/motor learning (gamma does not directly innervate skeletal fibers)
• on stretch, intrafusal gets excited

Question 59

What is muscle tone? When is it increased/decreased?

Answer 59

Muscle tone - resting tension in muscle produced by muscle elasticity
Hypotonia - spinal nerves damaged
Hypertonia - supraspinal lesions where stretch reflexes are increased
Measured by moving around limbs eg wrist rotation, flex/extension

Question 60

What is a circuit pattern generator?

Answer 60

biological neural networks that produce rhythmic patterned outputs without sensory feedback
eg continuous flexion/extension (walking on treadmill even if spinal cord has been transected)

Question 61

Describe spinal shock

Answer 61

spinal cord injury –> loss of all motor and autonomic function below the lesion for 1-6 weeks

• flaccid paralysis, bowel and bladder paralysis, loss of vasomotor tone (hypotension), loss of reflexes
• loss of descending facilitation that keeps spinal cord circuits in state of readiness
• loss of all sensation

Question 62

1. What are lower motor neurons (LMN)?
2. ID location in spinal cord
3. Which cranial nerves have LMN components? (“bulbar motor neurons”)
4. Describe the somatotopic organization of lower motor neurons in the spinal cord

Answer 62

1. LMN = neurons that innervate muscle; heavily myelinated, fast conducting
2. Location = cell bodies in brainstem (motor nuclei of cranial nerves) and spinal cord (ventral horn)
   - LMNs to one muscle span many spinal cord segments
3. CNs III, IV, VI (eye movement); VII (facial movements), V (jaw opening), IX, X, XI (laryngeal, pharyngeal, trap, sternocleidomastoid), XII (sticking tongue out)
4. Motor neurons innervating more distal muscles are more lateral in the grey matter, proximal muscles are more medial
   flexors are dorsal, extensors ventral

Question 63

Functions of the following LMN regions:

1. C3-C5
2. S3-S4
3. S2-S4

Answer 63

1. C3-C5: motor neurons to phrenic nerve –> controls diaphragm
2. S3-S4: Onuf’s nucleus - motor neurons innervating urethral and external anal sphincter –> voluntary control of urination/defecation
3. S2-S4: motor neurons to pelvic floor muscles

Question 64

Distinguish between the 3 types of motor units:

FF, FR, and S

Answer 64

Motor unit - motor neuron and the group of skeletal muscle fibers it innervates

1. FF = fast fatigable - large motor neurons –> innervate more forceful muscle fibers and greater number of fibers
2. FR = fatigue resistant - medium motor neurons –> innervate fewer muscle fibers (less forceful, less fatigable), stil contract rapidly
3. S = slow-fatigue resistant, weakest –> innervate least number of muscle fibers and smaller, low force fibers which contract slowly

S motor units recruited first, then FR, then FF to increase muscle force, recruited units increase firing rate –> recruiting bigger motor units + increased firing rate –> increased muscle contraction

Question 65

Main symptoms of lower motor neuron syndrome?

What are common conditions that cause LMN syndrome?

Answer 65

LMN = any lesion affecting lower motor neurons anywhere along their length – deficits in specific muscles that have lost their input

1. Muscle weakness - as measured by muscle strength tests
2. Muscle atrophy - muscles that cannot contract lose mass
3. Decreased reflexes
4. Decreased muscle tone due to hyporeflexia
5. Electromyographic changes - measures of denervation

Peripheral nerve lesion, spinal nerve lesion, cranial nerve lesion, strokes or tumors affecting alpha motor neurons in ventral horn or brainstem, polio, ALS, Guillan Barre, Werdnig-Hoffman

Question 66

Differentiate between 
paralysis
paresis
plegia
palsy

Answer 66

paralysis - weakness so severe that muscle cannot be contracted

paresis - weakness or partial paralysis

plegia - severe weakness or paralysis eg qaudriplegia

palsy - imprecise term for weakness or no movement

Question 67

What is the difference between fibrillation and fasciculations on electromyography (EMG)?

Answer 67

Fibrillation - only detected with EMG - short, spontaneous potentials produced by single muscle fibers –> represent unstable muscle fiber cell membrane –> sign of denervation

Fasciculations - larger potentials caused by spontaneous activity in motor unit(s) - twitches you can see in the muscle –> can be normal (fatigue) or sign of denervation/reinnervation (common in ALS)

Question 68

Describe the clinical features and pathophysiology of:

1. Werdnig-Hoffman disease,
2. polio
3. post-polio

Answer 68

1. Werdnig-Hoffman disease - spinal muscle atrophy (SMA I) - caused by degeneration of anterior/ventral horns; autosomal recessive –> symptoms include weakness and muscle wasting in limbs, problems sucking + swallowing + breathing (CNs) “floppy baby” disease
2. Polio - caused by poliovirus, which replicates in oropharynx/small intestine before spreading to CNS; attacks ventral horn motor neurons –> LMN syndrome with hypotonia, hyporeflexia, fasciculations, atrophy; chronic denervation causes type grouping of motor units
3. Post-polio - neighboring motor neurons sprout, which leads to recovery/stable period
   but this cannot be sustained –> recurrence of same symptoms = post-polio

Question 69

Describe the function of premotor cortical regions; what happens when there is damage?

Answer 69

• Idea about voluntary movement –> frontal lobe
• Organization/motor planning –> premotor cortical areas (supplementary motor area + premotor cortex)
• Info about spatial relationships –> posterior parietal cortex (primary somatosensory cortex + parietal association cortex)
• Execute –> primary motor cortex

Lesion to premotor cortex or posterior parietal cortex –> apraxia = difficulty in performing complex voluntary actions eg brushing teeth, buttoning although people still have muscle strength and tone

Question 70

What are upper motor neurons? Where are they located

Answer 70

UMNs are descending motor neurons from the cerebral cortex and brain stem

• majority from cortex cross midline in lateral white matter tract –> synapse on lower motor neurons in distal ventral horn –> innervate distal limb muscles (Skilled movements)
• majority from brainstem in medial white matter tracts –> synapse on lower motor neurons in medial ventral horn –> innervate axial and proximal limb muscles (posture and balance)

Question 71

What is the corticospinal tract?

Describe the pathway of the lateral and medial tracts

Answer 71

Corticospinal / pyramidal tract - primary pathway for goal-directed movements

• lateral is ONLY descending pathway to project directly to alpha LMNs of distal muscles
• lateral is ONLY pathway to generate fine movements of the fingers (fingers considered distal)

UMN cell bodies in precentral gyrus (primary motor cortex) –> posterior limb of internal capsule –> ventral portion of pons –> 80% of fibers decussate in medulla at the pyramids (lateral) and 20% continue down (ventral column)

• Lateral - fibers go down through spinal cord in lateral corticospinal tract –> project directly and indirectly to motor neurons in lateral ventral horn –> controls movement of distal contralateral muscles
• Anterior - fibers go down ventral column –> project bilaterally to motor neurons in medial ventral horn –> controls movement of trunk and ipsilateral proximal muscles

*NOTE: motor cortex cells code for movements, not single muscles

Question 72

Define the somatotropy of the lateral corticospinal tract in the cortex, brainstem, and spinal cord

Answer 72

Cortex - lower extremities are further posterior/medial (towards midline) and upper on the outer/lateral part of brain, as per homunculus

Brainstem - medulla is where pyramidal decussation takes place (80% of CST fibers)

Spinal cord - switched –> lower/distal muscles are on the lateral side of the ventral horn, upper muscles on the medial side

Question 73

What happens with lateral corticospinal tract damage above/below spinal cord?
Explain the Babinski sign

Answer 73

Lesion above spinal cord –> contralateral deficits
Lesions of spinal cord –> ipsolateral deficits (bc fibers have already crossed at pyramidal decussation)
deficits ALWAYS below level of lesion

Babinksi sign - extensor plantar response - stroke sole of foot –> big toe moves upwards and other toes fan out normal in infants before myelination
Healthy response –> flexion (toes curl down)

Question 74

Distinguish between function and anatomy of the medial and lateral spinal cord motor systems

Answer 74

Lateral motor systems (lateral corticospinal and rubrospinal tracts) project to lateral anterior horn cells –> control distal muscles of the extremities

Medial motor systems (anterior corticospinal,
vestibulospinal, reticulospinal, and tectospinal tracts) project to medial anterior horn cells –> control proximal trunk muscles

Question 75

Describe the following descending motor systems/brainstem pathways including incl sites of origin, decussation, termination, and function:
1. Reticulospinal tract

Answer 75

1. Reticulospinal tract - medial motor system
   A. Origin: pontine and medullary reticular formation
   B. No decussation - projects ipsilaterally
   C. Termination: goes down entire cord, projects to medial alpha motor neurons
   D. Function: posture, gait-related movements, `orward muscle activation (postural adjustments); tonic activity facilitates muscle tone

Question 76

Describe the following descending motor systems/brainstem pathways including incl sites of origin, decussation, termination, and function:
2. Vestibulospinal tracts (M and L)

Answer 76

2. Vestibulospinal tracts (Medial and lateral) - medial motor system
   A. Origin: Vestibular nuclei at ponto-medullary junction
   B. No Decussation - project to medial ventral horn
   C. Termination: (Medial) only cervical SC - projects bilaterally; (Lateral) down length of SC - projects ipsilaterally
   D. Function: (Medial) controls head position “vestibulocervical reflex” (Lateral) facilitates extensor muscle to help balance ; tonic activity facilitates muscle tone

Question 77

Describe the following descending motor systems/brainstem pathways including incl sites of origin, decussation, termination, and function:
3. Tectospinal tract

Answer 77

3. Tectospinal tract - medial motor system
   A. Origin: superior colliculus
   B. Dorsal tegmental decussation in midbrain
   C. Termination: cervical cord
   D. Function: Coordinating head and eye movement in response to visual/auditory input

Question 78

Describe the following descending motor systems/brainstem pathways including incl sites of origin, decussation, termination, and function:
4. Rubrospinal tract

Answer 78

4. Rubrospinal tract - lateral motor system
   A. Origin: red nucleus in the midbrain
   B. Ventral tegmental decussation in midbrain, travels next to LCST
   C. Termination: cervical spinal cord
   D. Function: facilitates flexor muscles (role in humans unclear)
   exception to rule that most brainstem pathways are medial

Question 79

What are symptoms of Upper motor neuron (UMN) lesions?

What is spasticity?

Answer 79

Initial shutdown of spinal circuits for several days (most severe being spinal shock - complete shutdown)

Followed by:

1. paresis - weakness of voluntary movements
2. Hyper-reflexia - change in descending influences
3. hypertonia - due to the hyper-reflexia, increased stretch reflex activity –> clasp-knife response initial resistance followed by inhibition of muscle
4. posturing - due to imbalanced muscle activity

2, 3, and 4 = spasticity
UMN damage disturbs balance of interneurons and motor neurons by descending pathways –> changes balance of motor neurons and reflexes; loss of inputs produces neuroplastic changes –> denervation supersensitivity and sprouting from local interneurons; reduces muscle extensibility due to muscle contracture –> increased muscle spindle activation

Question 80

Features of UMN syndrome:

What is clonus?

What is posturing in terms of decorticate vs decerebrate rigidity?

Hoffman’s sign?

Answer 80

Clonus - muscle spasming with repeated reflexes; occurs with severe hyper-reflexia

Posturing - produced by imbalanced muscle tone, bc of weakness and hypertonia
e.g. decorticate posture when lesions occur above midbrain –> upper limb is flexed, lower limbs extended
decerebrate lesion below midbrain –> all limbs extend (bc lesion is below red nucleus of rubrospinal tract- eliminates its flexor facilitation)

Hoffman’s sign - decreased ability to isolate movement - if you flex fingernail, thumb will flex and rebound into extension as well

Question 81

Compare LMN and UMN lesions in terms of: 
weakness
atrophy
fasciculations
reflexes
muscle tone 
paralysis

Answer 81

Weakness - UMN and LMN
Atrophy - LMN only
Fasciculations - LMN only
Reflexes - increased in UMN, decreased in LMN
Muscle tone - Increased in UMN, decreased in LMN
Paralysis - spastic in UMN, flaccid in LMN

*positive Babinski sign and clasp-knife spasticity in UMN

Question 82

Describe the function and location of the corticobulbar tract

Answer 82

Corticobulbar tract refers to UMNs from primary motor cortex; originate in primary motor cortex of frontal lobe (precentral gyrus) –> passes through genu of internal capsule (close to the corticospinal tract)–> to brainstem where there are CN nuclei with motor components –> synapse with LMNs

Innervation is bilateral EXCEPT contralateral to CNVII (lower face), and contralateral to CN XII (tongue)

bilateral innervation means that if there is a lesion - opposite side can take over; this does not happen with VII and XII –> get contralateral paralysis of lower face

Question 83

Differentiate between the effects of Bell’s palsy and a corticobulbar tract lesion

Answer 83

Bell’s palsy - cranial nerve VII lesion –> ipsolateral LMN paralysis of 1/2 of the phase; both upper and lower face affected on either R or L –> no eye closure, no mouth retraction (ie smile)

Corticobulbar tract lesion - happens at UMN level; since innervation to CN VII is bilateral for upper face and contralateral lower face –> lesion produces only opposite side lower face paralysis e.g. no mouth retraction (BUT can still occur voluntarily)

Question 84

What are causes of UMN syndrome?

Answer 84

Trauma
Stroke
Multiple sclerosis
ALS - motor neuron disease; degenerates UMN and LMNs
cerebral palsy - variety of non-progressive disorders caused at birth by trauma, ischemia –> spastic diplegia, intellectual disability, abnormal motor control

Question 85

Describe acute ischemic stroke

What is the difference between an ischemic stroke and hemorrhagic stroke?

Answer 85

Blood clot in artery –> blocks blood flow to part of brain; neurons around it die immediately, but other parts get collateral blood flow and create ischemic penumbra (neurons trying to survive) - try to save these neurons; 32,000 neurons lost in one second–> 120M in an hour (3.6 years aged)

Types of strokes:

• Ischemic (80%) due to bv (most commonly middle cerebral artery) becoming blocked by blood clot –> cerebral infarction (cell death due to hypoxia due to obstructed blood flow)
• Hemorrhagic (20%) due to rupture of artery hard to differentiate clinically –> do non-contrast head CT

Question 86

What are the indications/contraindications in TPA for stroke?

Answer 86

TPA (IV) - tissue plasminogen activator affects all parts of the body; based on time of onset, labs, EKG, head CT

TPA increases odds of going back to normal after stroke until 4.5 hours (OR=1)

Contraindications: active internal bleeding, intracranial hemorrhage, recent intracranial/spinal surgery, elevated PTT, platelet count, severe uncontrolled HTN, history of recent stroke

Question 87

Describe types of ischemic strokes including mechanism and risk factors:

1. Thrombotic
2. Lacunar
3. Embolic

Answer 87

1. Thrombotic - due to rupture of atherosclerotic plaque in larger bv (usually branch points eg bifurcations in Circle of Willis), risk factors: >40, preceding transient ischemic attacks (TIAs), vascular risk factors
2. Lacunar - due to hyaline arteriosclerosis - affects smaller bv perfusing deep areas of brain (e.g. lenticulostriate vessels)–> small cystic infarcts, milder symptoms, no cortical deficits (does not affect cerebral cortex)
3. Embolic - due to thromboemboli, most commonly from left side - severe deficit in a large zone with massive onset, Risk factors: atrial fibrillation. valvular disease, structural heart disease, paradoxical embolus (foramen that has not closed), aortic arch plaque, cardiac tumors

Question 88

Describe the rare causes of ischemic strokes:

1. Arterial dissection
2. Moya moya
3. Hypercoagulable states
   4) Vasculitis

Answer 88

1. Arterial dissection - due to trauma, bv forms blood clot in wall –> narrows bv and little pieces of hematoma can cause stroke
2. Moya moya - abnormally dilated collaterals due to damage in distal intercranial arteries - can be genetic eg sickle cell disease
3. Hypercoagulable states - clotting disorders due to mutations in factors VII, V, thrombin, platelets etc; typical of younger, female patients with history of miscarriages/FH of thrombosis
   4) Vasculitis - bv fibrose and become narrow as they heal from inflammation –> bv normal, narrow, dilates again; typical of younger patients with headaches, cognitive decline and recurrent strokes

Question 89

Describe the types of hemorrhagic stroke:
1. Intracerebral
A. Hypertensive
B. Lobar

Answer 89

1. Intracerebral - bleeding into brain tissue

A. Hypertensive - most common cause of intracerebral; deep e.g. in basal ganglia/thalamus, due to Charcot-Bouchard aneurysms (rupture of small penetrating arterioles) –> headache, confusion, lethargy

B. Lobar - due to:

• tumors
• vasculopathy (moya moya, vasculitis)
• drugs (cocaine)
• AV malformations (artery connected directly to vein without capillary network)
• trauma (frontal, occipital, temporal lobes)
• coagulopathy - anticoagulants, platelet dysfunction –> hemorrhage appears as a line, not a circle
• cerebral amyloid angiopathy - age >60, multiple lobar hemorrhages due to amyloid deposits in arterioles

Question 90

Describe the types of hemorrhagic stroke:

2. Subarachnoid

Answer 90

2. Subarachnoid - bleed in subarachnoid space that outlines the brain –> causes chemical meningitis
   - Symptoms: “worst headache of life,” neck stiffness, nausea, lethargy
   - Causes: trauma, rupture of Berry aneurysms at branch points, AV malformations
   - Complications: rebleeding, vasospasm, hydrocephalus

Question 91

What are the most sites of hemorrhagic strokes?

Answer 91

50% occur at basal ganglia/thalamus (deep, due to HTN)
33% occur at lobar
17% at brainstem/cerebellum

Question 92

Describe the mechanisms of venous stroke

Answer 92

Venous sinus can get thrombosed (most commonly transverse or superior sagittal sinus)–> cannot resorb venous blood
since there are other veins, can compensate for a while, but at some point brain begin to swell

Mechanism:

1. Thrombosis of cerebral veins –> increased venous pressure
2. Recruitment of collaterals (initially compensates)
3. Compensatory failure (vasogenic edema due to BBB disruption –> increased intravascular pressure)
4. Parenchymal lesions –> failure of energy metabolism, can be hemorrhagic (venous rupture) and ischemic (cytotoxic edema)

Question 93

What is a sensory neuropathy? What are positive and negative symptoms?

Answer 93

Sensory neuropathy - disorder in sensory nerves caused by a lesion

Negative - loss of sensation

• analgesia (loss of pain w/out loss of feeling/movement)
• anesthesia (loss of touch / all feeling)

Positive - abnormal sensory phenomenon

• paresthesias - abnormal pain sensation, usually temporary mild pain “pins and needles”
• neuropathic pain / Central Pain Syndrome - chronic intense pain “shooting, stabbing”

Question 94

Describe the receptors and somatic sensory afferents for the different somatosensory modalities for sensory stimuli:

1) Touch/Vibration
2) Proprioception
3) Temperature
4) Pain

Answer 94

1) Touch/Vibration - cutaneous mechanoreceptors, responds to pressure; Abeta fibers
- Meissner corpuscle (light touch, motion)
- Merkel cell (pressure, discriminating shape, texture)
- Ruffini corpuscle (skin stretch)
- Pacinian corpuscle (vibration sense)

2) Proprioception - muscle and joint mechanoreceptors, responds to displacement; Ia and II fibers
- muscle spindle (1a afferents, gamma motor neuron) –> detects muscle length
- Golgi tendon organ (1b afferents) –> detects muscle tension

3) Temperature - responds to cold and warm thermoreceptors
- free nerve endings; Adelta and C fibers
* each thermoreceptive neuron only expresses 1 type of temperature receptor

4) Pain - can be polymodal, thermal, or mechanical nociceptors
- free nerve endings; Adelta and C fibers

Proprioception receptors have largest diameter and most myelination, fastest conduction velocity –> then touch, then pain

Question 95

What are the 3 major long pathways in the CNS? Incl modality and site of decussation?

What are the similarities/differences bw DCLMS and STT?

What are symptoms of lesions of DCLMS and STT?

Answer 95

1. Corticospinal Tract - Motor - decussates at medullary pyramids
2. Dorsal Column-Medial Lemniscus System (DCLMS) - Sensory (vibration, joint position/proprioception, fine touch) - decussates at internal arcuate fibers of lower medulla
3. Spinothalamic Tract (STT) - Sensory (pain, temp, crude touch) - decussates at anterior commissure of spinal cord

DLCMS and STT both sensory, use dorsal root ganglion as primary neuron, have 3 neurons in pathway + 2 relay points, both cross to contralateral side, and have receptors all over body
Differences - receptors, types of dorsal root ganglion neurons, morphology

DCLMS lesion –> tingling, tight sensation around trunk/limbs, feeling of gauze on fingers, Lhermitte’s sign (electricity down back/extremities upon neck flexion)
STT lesion –> sharp, burning, searing pain

Question 96

Describe the following mechanisms by which nervous system encodes sensory stimuli:

1. Intensity
2. Timing
3. Location

Answer 96

1. Intensity - sensory threshold is determined by sensitivity of receptors; stroking palm is low threshold, touching oven sensory receptors are high threshold
2. Timing - receptors differ in timing of response to stimulus; slowly adapting receptors are tonic - initially fire rapidly then detect static qualities eg feeling of leg touching chair; rapidly adapting receptors are phasic and detect dynamic qualities at stimulus then stop firing eg stroking palm
3. Location - affected by receptor density, receptive field, and inhibitory mechanisms
   - two point discrimination threshold smaller on fingers than thigh or calf
   - fingertips and palm have higher receptor density than forearm or trunk
   - receptors in receptive field stimulated, those right outside are inhibited to distinguish the boundary of the stimulus

Question 97

Describe the Dorsal Column Medial Lemniscus System Pathway (DCMLS)

Answer 97

DCMLS: Modality = vibration, proprioception, fine touch

1. Sensory nerve ending of Adelta and C fibers with cell body in dorsal root ganglion
2. 1st neuron axon ascends spinal cord ipsilaterally in dorsal/posterior column –> lower body through gracillus tract, upper body through cuneate tract
3. Synapse 1 on gracile and cuneate nucleus in medulla
4. 2nd neuron axon decussates at internal arcuate fibers of lower medulla
5. Ascends contralaterally in medial lemniscus (ribbon of cells through rostral medulla)
6. Synapse 2 in Ventral Posterior Lateral (VPL) nucleus of thalamus
7. 3rd neuron goes up to primary somatic sensory cortex in postcentral gyrus

Question 98

Describe the Trigeminal Mechanosensory System

Answer 98

Modality = touch and vibration information from face to cortex - contralateral (decussates in pons)

1. First order neuron comes from mechanosensory receptors in face through trigeminal nerve (cell body in trigeminal ganglion)
2. Synapse 1 on principal nucleus of trigeminal complex in pons
3. Second order neuron decussates in pons and ascends in trigeminal lemniscus (next to medial lemniscus)
4. Synapse 2 on Ventral Posterior Medial (VPM) nucleus of thalamus
5. Third order neuron goes to primary somatic sensory cortex

*lesion below pons –> do NOT lose facial sensory info

Question 99

Describe the spinocerebellar tracts

Answer 99

Modality = proprioception
proprioception sensory fibers synapse in Clark’s nucleus, ascend via spinocerebellar tract ipsilaterally up to the cerebellum (balance)
Multiple tracts including posterior, anterior, rostral, etc - involving large diameter sensory neurons

*spinal columnar lesion not damaged in isolation - usually with dorsal column nuclear (DCLMS) lesion –> fail Romberg test (fall over when eyes are closed) e.g. tabes dorsalis (syphilis), subacute combined degeneration (B12 deficiency) –> both cause ataxia

Question 100

Describe the connections to and organization of the primary somatosensory cortex

Answer 100

Primary somatosensory cortex is in the postcentral gyrus

1. Info from head (mechanosensory and pain/temp via trigeminal nerves)–> Ventral posterior medial (VPM); info from body (STT and DCMLS) –> Ventral posterior lateral (VPL) nuclei of the thalamus
2. Four regions of primary somatosensory cortex –> each contains full homunculus (convey diff info bc of diff receptors)
3. Provides info to secondary somatic sensory cortex –> amygdala and hippocampus
4. Provides info to posterior parietal cortex –> motor and premotor cortical areas

Question 101

Describe the tests for cortical sensory loss:

1. Sterognosis
2. Graphesthesia
3. Double simultaneous stimulation

Answer 101

1. Sterognosis - different orientations of the item eg vertical, horizontal
2. Graphesthesia - different directions of the item eg drawing letters on palm
3. Double simultaneous stimulation (tests posterior parietal cortex regions 5 and 7) - if patient has lesion on R side and you touch both R and L sides –> would only feel on R side

Question 102

Describe the spinothalamic (STT) system pathway

Answer 102

Modality: pain, crude touch, and temperature

1. Adelta and C fibers = first order neurons go up and down before entering dorsal root (cell bodies in dorsal root ganglion)
2. Synapse 1 in Lissauer’s tract (ipsilateral gray matter in spinal cord)
3. Second order neurons decussate in anterior/ventral white commissure in spinal cord– takes 2 segments to fully decussate to anterolateral side
4. Ascends via anterolateral system
5. Synapse 2 in VPL nucleus of thalamus
6. 3rd order neuron goes to primary somatosensory cortex (postcentral gyrus)

Question 103

Describe the trigeminal system for pain/temp

Answer 103

Modality: pain/temp to the face - ipsilateral (no decussation)

1. pain and temp info from face goes through trigeminal ganglion to pons
2. First order neuron descends via spinal trigeminal tract to medulla
3. Synapse 1 - spinal nucleus of trigeminal complex in medulla
4. Second order neuron ascends via trigemino-thalamic tract
5. Synapse 2 - VPM of thalamus
6. Third order neuron goes to primary somatosensory cortex

Question 104

Describe the reason behind phantom limb pain

Answer 104

After amputation - reorganization of somatosensory cortex so that neurons that used to be innervated by amputated limb now respond to stimulation from other parts of the body - causes intense pain
eg touch patients face and they feel their phantom limb is being touched (face and hand v close on homunculus)
*can treat with mirror therapy

Question 105

Describe different presenting symptoms with different types of peripheral neuropathy:

1. Peripheral nerve
2. Small fibers
3. Myelin
4. Sensory ganglia lesions

Answer 105

Peripheral neuropathy: lesions affecting PNS –> weakness, numbness, pain, and tingling/burning from nerve damage

1. Peripheral nerve –> all fiber types –> sensory, motor, and autonomic systems e.g. weakness and sensory loss
2. Small fibers –> pain, temperature, and autonomic loss
3. Myelin –> in large fibers –> vibration and position sense loss, motor loss
4. Sensory ganglia lesions –> only sensory symptoms

Question 106

What is the difference between neuropathic and nociceptive pain?

What is the difference between radiculopathy, mononeuropathy, and polyneuropathy?

Answer 106

1. Nociceptive - tissue damaged, but nerves intact
   Neuropathic - lesions in PNS and CNS –> burning, stinging, shooting pain + areas of numbness
   eg herpes zoster, trigeminal neuralgia; use anti-epileptic and antidepressants
2. Radiculopathy - lesion to nerve root (compressed disc)–> sensory symptoms of numbness and tingling that follow dermatomal pattern eg herpes zoster (dorsal root ganglion)
   Mononeuropathy - lesion to peripheral nerve (trauma) –> sensory, motor, and autonomic symptoms eg carpal tunnel syndrome
   *both are types of focal lesions
   Polyneuropathy - affects distal ends of many nerves via generalized process in “glove and stocking” pattern (diabetes, alcohol, Vit B12 def.); diffuse pain

Question 107

Describe pathology of damage to axons vs myelin

Answer 107

Damage to Axons - Wallerian degeneration “dying forward” – distal axonal degeneration, and myelin breaks up –> chromatolysis of cell body +recruitment of macrophages (visualize as swellings along axons) –> some regeneration afterwards
* can also have “dying back of axons” due to metabolic diseases that affect health of neuron

Damage to myelination - “segmental demyelination” when myelin sheaths damaged by trauma/disease most susceptible part of PNS to trauma

• symptoms picked up by nerve conduction test –> slowed conduction velocity or conduction blocks
• myelin can return in days to weeks; “concussion” - affects quickly and is able to recover

only axon damage leads to muscle atrophy!

Question 108

Describe the clinical features and pathophysiology of following types of non-traumatic peripheral neuropathies:
1. Diabetes

Answer 108

1. Diabetes greatest source of morbidity and mortality

A. Clinical features: 80% have length-dependent diabetic polyneuropathy (longest axons affected) –> Systems begin in feet and move up “glove and stocking” of sensory loss + motor weakness –> paresthesia, numbness, tingling, calluses

B. Pathophysiology: axonal degeneration, dying back, demyelination, effects related to ischemia + oxidative stress
sensory more affected –> small fiber polyneuropathy

Question 109

Describe the clinical features and pathophysiology of following types of non-traumatic peripheral neuropathies:
2. Vitamin B12 deficiency

Answer 109

2. Vitamin B12 most common metabolic neuropathy

A. Clinical features: symptoms mainly in distal limbs (upper); demyelinating –> loss of vibration sense (from large fibers which carry mechanosensory info)
-can also cause subacute combined degeneration –> posterior and lateral columns affected –> Ataxia + spasticity

B. Pathophysiology: need B12 to produce myelin and RBCs, gotten through animal protein and can cause pernicious anemia

• needs to be differentiated from MS
• treatment is B12 therapy

Question 110

Describe the clinical features and pathophysiology of following types of non-traumatic peripheral neuropathies:
3. Guillan Barré Syndrome

Answer 110

3. Guillan Barré = acute inflamamtory demyelinating polyneuropathy most common cause of acute paralysis seen in clinical practice

A. Clinical features: primarily motor with ascending symmetric paralysis, but may begin with paresthesia in toes/fingers
Diagnostic tests:
-nerve conduction velocity decreased
-increased protein in CSF

B. Pathophysiology: begins 1-3 weeks post infection/vaccination –> inflammatory attack on peripheral myelin –> Segmental demyelination

Question 111

Describe the clinical features and pathophysiology of following types of non-traumatic peripheral neuropathies:
4. Charcot-Marie-Tooth

Answer 111

4. Charcot Marie Tooth disease - group of hereditary demyelination diseases that affect myelin (CMT1) or axons (CMT2)

A. Clinical features: CMT1 most common - combined motor sensory neuropathy, primarily distal muscle - hammertoes

• reduced conduction velocity
• does not affect pain/temp (those are small fibers)

B. Pathophysiology: hereditary, fewer number of myelinated axons in peripheral nerves

Question 112

What are the symptoms of Brown-Seqaurd syndrome (hemicord lesion)?

Answer 112

1. level of lesion: loss of all sensation + ipsilateral LMN signs (e.g. flaccid paralysis)
2. below level of lesion:
   - lateral corticospinal tract damage –> ipsilateral UMN weakness
   - dorsal column damage - ipsilateral vibration/proprioception weakness (also two-point discrimination)
   - spinothalamic/anterolateral column damage 2 segments below –> contralateral pain and temperature weakness

IF lesion occurs above T1 –> Horner’s (miosis, ptosis, anhidrosis)

Question 113

Define the temporal components of pain

Answer 113

Adelta - first pain (sharp, more intense) - fast, myelinated
C fibers - second pain (more long-lasting) - slow, unmyelinated

can selectively block Adelta or C fibers e.g. local anesthetics block Na+ channels to prevent conduction of impulses along C fibers

recessive loss of function mutation to sodium channel –> insensitivity to pain
dominant gain of function –> extreme pain

Question 114

What are the 3 anterolateral pathways involved in pain and what are their specific functions?

Answer 114

Spinothalamic tract (STT) - discriminative aspects of pain and temp (location, intensity, quality)

Other two mediate affective-emotional aspects of pain (Centers are anterior cingulate cortex and insular cortex) - goes through midline thalamic nuclei

Spinoreticular tract -emotional aspects of pain (unpleasant - sweating/scared feeling, activates autonomic flight or fight reaction)
*exits STT pathway –> Reticular formation in pons

Spinomesencephalic tract - central modulation (descending control to reduce pain sensation)
*exits STT pathway in the midbrain –> periaqueductal gray –> release of endogenous opioids from interneurons –> decreased C fiber activation of dorsal horn projection neurons

Question 115

Explain the types of sensitization to sensory stimuli.

Explain process of peripheral sensitization

How does capsaicin act as an analgesic?

Answer 115

1. Sensitization - when neighboring nociceptors that were previously not responsive become responsive due to repeated application of noxious stimuli
   Two levels:
   A. hyperalgesia - stimuli that are normally perceived as painful become MORE painful (eg pinprick to sunburnt skin)
   B. alloydnia - stimuli that is not normally painful is painful (eg swallowing with sore throat)
2. Peripheral sensitization - many substances decrease threshold of activation for nociceptors
   - prostaglandin - lowers threshold for DRG neurons
   - substance P –> bv vasodilation, degranulation of mast cells –> histamine
3. Topical capsaicin –> desensitization of C fibers + depletes Substance P –> blocks peripheral sensitization

Question 116

What is central sensitization and the 2 main mechanisms?

Answer 116

Central sensitization - immediate increase in excitability of neurons in dorsal horn of spinal cord, following high level of nociceptive afferent activity

1. Wind-up - transcription independent - acute, lasts only during stimulation –> more activation of secondary neurons with repeated stimulus
2. Allodynia - transcription dependent - chronic, mediated by COX
   - reduced threshold for activation by peripheral
   - expansion of receptive field size
   - increase in spontaneous activity
   - Mg2+ block released from NMDA receptor –> chronic activation

Question 117

Explain the ways that pain sensation can be modulated by descending mechanisms

Answer 117

• stress-induced analgesia e.g. wounded soldier
• placebo effect (75% respond, can be blocked by naloxone)
• overlap of brain activation between pain and meditation
• descending pathway from cortex –> insula –> amygalda –> periaqueductal gray –> rostral ventral medulla -> dorsal horn where interneurons release endogenous opioids –> inhibit C fibers from sending more pain signals back up to primary somatosensory cortex via spinomesencephalic pathway

Question 118

What is the Gates Theory of Pain?

Answer 118

Local modulation of nociceptive information - pain results from balance of activity in nociceptive vs non-nociceptive afferents

TENS (nerve stimulation such as rubbing knee) activates large Abeta fiber mechanoreceptors –> synapse with interneurons in dorsal horn of spinal cord –> interneurons contain endogenous opioids (enkephalins, endorphins, dynorphins) –> inhibit C fibers –> second order neuron inhibited –> reduced pain going up to cortex

Question 119

Describe the pathways for visceral and referred pain

Answer 119

1. Visceral pain (from thoracic, pelvic, abdominal organs) fibers go through DRG and up the spinal cord –> synapse in gracile nucleus –> second order projection neuron ascends via dorsal column / medial lemniscus –> through ventral posterior nucleus of thalamus –> insular cortex
   * can eliminate through cordotomy - by selectively cutting neurons in dorsal spinal cord
2. Referred pain - most pain from viscera conveyed via dorsal column pathway
   HOWEVER second order projection neuron carries signals/has synapses converging from both skin and viscera –> cannot distinguish where pain originated

Question 120

Differentiate between amide and ester local anesthetics

For local anesthetics, describe:

1. MOA
2. chemical structures
3. effects of pH

Answer 120

Ester - e.g. cocaine; less stable - shorter duration of action
Amide - e.g. lidocaine; more stable, metabolized by cypP450 in liver

1. MOA - reversible binds to and blocks sodium channel in excitable membranes without changing resting potential–> reduces inward Na+ current –> prevents action potential –> blocks impulse conduction along nerve axons
2. Chemical structures - aromatic ring, intermediate chain (ester or amide), ionizable group (tertiary amine)
3. LAs are weak bases, want to be as close to ambient pH as possible to have equal ratio of ionized and non-ionized –> neutral form to diffuse to site of action, ionized form to bind to Na+ channel

Question 121

Explain Modulated Receptor Hypothesis

Explain Frequency Dependent Block

Answer 121

1. Modulated Receptor Hypothesis: LA binding is a function of the conformational state of the channel –> LAs have higher affinity for receptors in activated and inactivated states, less so for resting state (-90 mV, activation gate closed)
2. Frequency Dependent Block: fibers that fire at faster rate are more susceptible to LAs, and repeated depolarizations produce more effective LA binding

Question 122

Describe the following properties of LAs:

1. lipophilicity
2. pKa
3. protein binding

What is the impact of vasoconstrictors as it relates to absorption and duration of LAs

Answer 122

1. increased lipophilicity increases potency, duration, and onset of action
2. increased pKa increases onset of action
3. Increased protein binding increases duration of action (hard to metabolize)

Vasoconstrictors eg epi - decrease absorption of LAs but particularly effective for short/medium acting drugs –> increases tissue binding –> increased duration of action

Question 123

What are the clinical uses of LAs?

Describe nerve sensitivities to LAs for neuraxial and peripheral blocks

Answer 123

• topical
• infiltration
• peripheral block - plexus anesthesia (bundle), individual nerve block, IV regional Bier block
• neuraxial blocks - spinal (low volume, short acting, goes through dura into CSF), epidural (high volume, larger volume)

Neuraxia (eg epidural/spinal tap): autonomic and pain fibers most sensitive, then sensory, then motor (bc of size and arrangement)
Peripheral: motor –> proximal sensory –> Distal sensory (bc of motor fibers are more peripheral and sensory more central)

Question 124

Describe adverse effects of LAs:

1. Systemic toxicity
2. Local toxicity
3. Allergic rxns
4. Methemoglobin formation

Answer 124

1. Systemic toxicity - inject too much LA –> affects excitable membranes other than target nerves, effect proportional to serum LA concentration
   CNS toxicity –> give propofol –> cardiotoxicity give IV lipid emulsion
2. Local toxicity - neural injury due to high concentrations for extended period –> motor and sensory loss; transient neurologic symptoms (TNS) NOT associated with motor/sensory loss
3. Ester metabolism results in PABA –> hapten formation –> IgE mediated allergic reaction; amide allergy rxns v rare
4. Methemoglobinemia - due to prilocaine which acts as oxidizing agent –> chocolate colored blood treat with methylene blue

Question 125

Describe facts about selected LAs: 
I. Esters
a. Cocaine
b. Benzocaine
c. Tetracaine
d. Procaine 
e. Chloroprocaine

II. Amides

a. Lidocaine
b. Mepivicaine
c. Prilocaine
d. Bupivicaine
e. Ropivicaine

Answer 125

I. Esters - short acting

a. Cocaine - stimulant, vasoconstrictor
b. Benzocaine - topical,
c. Tetracaine - long duration, toxic at low doses
d. Procaine (Novacaine) - leads to TNS, hypersensitivity
e. Chloroprocaine - quick onset and short duration (use at end of labor)

II. Amides - long acting

a. Lidocaine - quick onset, moderate duration; implicated in TNS
b. Mepivicaine - lowest pKa, vasoconstrictor
c. Prilocaine - associated with methemoglobinemia
d. Bupivicaine - cardiac toxicity
e. Ropivicaine - long duration, less cardiotoxic
* prilocaine + lidocaine = EMLA (topical)

Question 126

Describe opiate, opioid, and endogenous opioid peptides

Answer 126

1) opiate - naturally occurring opium-derived alkaloid i.e. morphine, codeine
2) opioid - natural or synthetic compound with morphine-like properties, mostly mu receptor agonists
3) endogenous opioid peptides e.g. endorphins, enkephalins - located in brain and function as neurotransmitters, modulate pain transmission (spinal cord) and alter Ach release (GI myenteric plexus)

Question 127

1. Describe the action of opioids in analgesia

2. Describe major uses of morphine/opioids in the clinic

Answer 127

1. MOA - inhibits cAMP formation + Ca2+ uptake in presynaptic neuron –> inhibits release of glutamate and substance P
   opens K+ channel in postsynaptic neuron –> hyperpolarization of neuron –> dampens firing –> reduces neuron excitability and pain
2. • analgesia for acute pain e.g. MI, severe injuries EXCEPT head injury, post-surgery, cancer (fentanyl)
   • more effective in prolonged, burning pain*
   • analgesia for chronic pain (oxycodone)
   • anesthesia (fentanyl)
   • cough suppressant (codeine)
   • relief from diarrhea (diphenoxylate, loperamide)
   • acute pulmonary edema (morphine)
   • relieve labor pain BUT fetus also gets the drug –> can cause respiratory depression or physical dependence in utero

Question 128

Describe the acute effects of opioids incl effects on CNS, cardiovascular, GI

Answer 128

• true of all mu opioid agonists*
• analgesia - both CNS and PNS
• euphoria - suppress release of GABA –> stimulate release of dopamine in neighboring neuron
• sedation - more likely in elderly or those taking other depressants
• miosis (except meperidine) - stimulates parasympathetic nucleus in oculomotor CN III sign of OD
• respiratory depression - decreased sensitivity to C02 –> cerebral vasodilation –> increased intracranial pressure can make head injury worse, sleep makes worse so keep patient awake, almost always cause of death from OD
• constipation - spasm of smooth muscle along GI tract can precipitate gallstones
• cough suppression - depresses cough centers in medulla via different mechanism
• nausea, vomiting - stimulates trigger zone –> activates vomiting center esp in ambulatory patients
• muscle rigidity
• bradycardia - stimulation of vagus nerve CN X
• histamine release - urticaria, pruritis not an allergy

Question 129

.1 Describe the chronic effects of opioids

2. Explain the role of methodone in treating opioid addiction
3. Describe opioid overdose
4. Compare pharmacokinetics of morphine, fentanyl, methadone

Answer 129

1A. Tolerance - reduced effect with repeated dosing + cross-tolerance to other opioids; develops rapidly to analgesia, euphoria, respiratory depression but not to miosis, constipation i.e. addicts get little euphoria from high doses but still experience miosis and constipation
B. physical dependence - (not psychological addiction to high) withdrawal symptoms when stopped e.g. sweating, vomiting, chills - giving naloxone precipitates more severe withdrawal

2. Methadone is long-acting opioid used for detoxification –> given orally and has much longer half-life –> intensity of withdrawal symptoms decreased –> then give naltrexone for maintenance
3. Opioid overdose - respiratory depression!
   classic triad - miosis, apnea, coma
   give naloxone
4. Morphine is rapidly absorbed, widely distributed, quickly cleared by kidney; hydrophilic –> takes while to enter CNS –> slow onset and long duration
   Fentanyl –> 100x more powerful than morphine; lipophilic -> crosses BBB; short half-life and high metabolism

Question 130

Describe the role of opioid antagonists, partial agonists, and mixed agonist-antagonists for opiate detoxification in the clinic

Answer 130

1. Opioid antagonists - displace morphine from its mu receptor
   A. Naloxone - drug of choice for OD
   -rapid-acting but short duration; immediate relief from respiratory depression
   -not orally active (IV or IM)
   -added to opioid drugs to make them abuse resistant - if drug is misused and injected –> induces withdrawal symptoms

B. Naltrexone - long-acting opioid for maintenance therapy to prevent relapse once patient is detoxified
*NOT used for emergency OD or detoxification

2. Partial agonists at mu receptor - buprenorphine, has analgesic properties and ability to antagonize morphine effects
3. Mixed agonist-antagonists - act as K agonists to produce analgesia and mu antagonists –> can induce acute withdrawal; effective analgesic but not adopted in the US

Question 131

Describe the inflammatory response to CNS injury e.g. spinal cord injury and Sequelae

What are the differences bw CNS and PNS response to injury

Answer 131

1. Injury –> microglia activated and change to ameboid shape –> secrete cytokines and become phagocytic –> activated macrophages come in –> neuropathic pain + chronic inflammation (microglia hang around for years)
2. Sequelae:
   - secondary cell loss (due to Ca2+ influx)
   - breakdown of b/b barrier
   - reactive astrocytes undergo gliosis (get larger) –> seal off broken BBB –> create glial scar –> environment is hostile to axonal regeneration (inhibitory factors include cellular debris, Nogo, proteoglycans)
3. can have axonal regrowth with PNS injury to epinerium bc environment is permissive
   CNS axons maybe able to regenerate given appropriate environment, but as is they are not able to grow past the injury site

Question 132

Describe clinical management of spinal cord injury

Answer 132

1) manage inflammatory response e.g. EPO, methylprednisolone (Steroid)
2) Surgical - decompress and stabilize spine, peripheral bridging
3) Rehabilitation - improve functional recovery and systemic immune function
4) biochemical - overcome inhibitory factors e.g. inhibiting Nogo - which itself inhibits myelin
5) cellular - provide substrate for axonal regeneration; cell replacement with mesenchymal stem cells, olfactory ensheathing cells, bone marrow stromal cells –> get remyelination

Question 133

Multiple sclerosis:

1. Etiology/risk factors
2. Pathogenesis
3. Symptoms
4. Management

Answer 133

MS - immune-mediated demyelinating disease of CNS; UMN disorder

1. Etiology - cause unknown but most likely autoimmune; risk factors include genetics, environment (EBV infection), smoking
2. Pathogenesis - lymphocytes in white matter plaque –> inflammation –> demyelination via oligodendrocyte loss –> neurodegeneration (brain atrophy) with axonal loss –> repair inhibited by astrocyte activation and gliosis
3. Symptoms - fatigue/depression, trigeminal neuralgia (facial pain), myelitis (weakness), optic neuritis (blurred vision)
4. Management -
   - treat relapse (focal disturbance >24hrs) with IV steroids, ACTH, or IVIg
   - decrease frequency of relapses/delay progression with DMTs (disease modifying treatments) - e.g. natalizumab which blocks VLA4 and prevents immune cells from crossing BBB

Question 134

1. Describe types of MS and diagnostic criteria

2. What are common diseases that can mimic MS?

Answer 134

1. Types - relapsing-remitting (RRMS) –> secondary progressive (SPMS)
   OR primary progressive (PPMS)

Diagnostic criteria:

• need to have 1 clinical attack (24hrs+)
• dissemination in time (2nd episode or new lesion on brain MRI)
• dissemination in space (multifocal symptoms or multiple lesions)
• exclude mimic disorders (via history, MRI, lab)
• 1 yr progression for PPMS

2. Mimics:
   - lyme disease - v hard to distinguish
   - ADEM (acute disseminated enchephalomyelitis) - post virus or vaccination
   - neuromyelitis optica (demyelination of optic nerves) - has specific IgG
   - Vitamin B12 -lesions secondary to subacute combined degeneration
   - lupus - white matter lesions but different neuro signs (seizure, stroke, movement disorders)

Question 135

What is the function of the vestibular system?

What are the functions of the vestibular nuclei?

Answer 135

Senses movement through space and senses head position; Functions in conjunction with vision and somatosensation - need at least 2/3 to function

• vestibulospinal reflexes to compensate for head movements
• vestibulo-ocular reflexes to keep eyes still when head moves
• only system that projects directly to cerebellum

Lateral - control of posture, vestibulospinal reflexes
Medial and Superior - vestibulo-ocular, vestibulo-cervical reflexes
Inferior - integration from vestibular labyrinth and cerebellum

Question 136

1. Describe the anatomy of the vestibular organs including cupula, utricle, saccule
2. Describe the morphology and function of vestibular hair cells

Answer 136

1. Bony labyrinth contains vestibule, cochlea, and 3 semicircular canals that work in pairs; within it is membranous labyrinth/scala media (filled with K+ rich endolymph) and surrounded by perilymph (low in K+) –> creates charge crucial for hair cells
   - cupula (in semicircular canals)works best with angular acceleration - covers the ampulla (epithelium of hair cells) - is displaced by movement and moves hair cells in opposite direction

• Otolith organs = utricle and saccule, work best with linear acceleration of head
• utricle contains macula with hair cells in horizontal plane oriented towards striola–> degree of pitch
• saccule contains macula with hair cells in vertical plane oriented away from striola –> Degree of roll

2. Type I hair cells more sensitive, Type II less so; sit on receptor sheet with kinocilium at one end (when bent –> opens ion channels)
   - if hair cells bend towards kinocilium –> depolarization –> increase firing rate of afferent
   - if hair cells bend away –> hyperpolarization –> decrease firing rate
   - SO if you turn head to left –> hair cells in left semicircular canal turn towards kinocilium (increased activity) and those on the right turn away (decreased)

Question 137

Describe conditions related to the vestibular system:

1. Meniere’s disease
2. Nystagmus

Answer 137

1. Meniere’s disease - overproduction of endolymph –> vertigo, tinnitus
2. Nystagmus - involuntary rhythmic eye movement
   named for fast component (OPP side of damage)
   - can induce via rotation test (normal eyes move in opposite direction of spin) or caloric test (cold water in ear, eyes move in same; warm water, opposite; COWS mnemonic describes nystagmus direction) –> no response is called canal paresis

Question 138

Describe how the conduct apparatus transforms sound pressure waves into mechanical vibrations

Answer 138

Bony labyrinth (same structure that houses vestibular system)

External auditory meatus –> tympanic membrane –> malleus –> incus –> stapes –> moves fluid (which has round window of overflow) –> vibrations converted to high pressure and come to oval window in fluid-filled cochlea –> basilar membrane and organ of corti (sensory epithelium) moves up and down –> stereocilia bend and inner hair cells move as well toward basal body (NOT kinocilium)–> depolarize and open ion channels

*inner hair cells detect sound, outer hair cells amplify and dampen the sound (can control movement of basilar membrane)

Question 139

Explain mechanism for detection of sound pitch and intensity

Explain mechanism for localization of sound in space

Answer 139

• volley principle - can cover entire range of frequency by having neuron skip a few beats
• phase locking
• basilar membrane stiff near oval window, flexible near apex of cochlea- high frequencies will get most movement at base, low frequencies at apex
• deafness in one year comes from lesion to VIII, or peripheral apparatus - not central auditory pathway bc cochlea is bilateral there

localization of sound in space:

• time difference via medial superior olivary nucleus (low frequency best)
• intensity difference via lateral superior olivary nucleus (high frequency best)

Question 140

1. Describe major effects of general anesthetic
2. Differentiation between general anesthesia and sedation
3. What is balanced anesthesia?

Answer 140

1. General anesthetic - unconscious, amnesic, analgesic, attenuates autonomic reflexes, relaxes skeletal muscle
2. Conscious sedation - awake, remember, and able to respond + protect airway (local anesthetic) vs general anesthesia (unable to protect airway)
3. Balanced anesthesia - using subclinical doses of multiple drugs to minimize side effects and maximize synergies

Question 141

Inhaled anesthetics:

1. What is the difference between gaseous vs volatile anesthetic?
2. Difference between onset and emergence
3. What is minimal alveolar concentration?
4. Effect of inhaled anesthetic on organ systems
5. What is malignant hypthermia?

Answer 141

1. Gaseous - only nitrous oxide, quick on/off, good amnestic and analgesic actions
   Volatile - liquid at room temp, mostly halogenated ethers (“fluranes”), primarily used for maintenance (induction in kids)

2A. Onset - uptake based on alveolar fraction Fa; anesthesiologist can increase onset through F1 (inspired fraction) and alveolar ventilation
-more insoluble - faster onset e.g. N20
B. Emergence - inverse of onset BUT you turn off agent so F1 is 0 and therefore alveolar ventilation is most important

3. MAC - measure of potency - partial pressure of inhaled anesthetic in alveoli at which 50% of population remain immobile; lower the MAC –> more potent
4. Decreased BP, decreased minute volume, no change in liver enzymes
5. Malignant hyperthermia - hypermetabolic syndrome after exposure to triggering agents (e.g. succinylcholine); increased Ca2+ –> muscle contraction –> hyperthermia/capnia/kalemia

Question 142

IV anesthetics:

1. Difference between onset and emergence
2. Propofol
3. Etomidate
4. Ketamine
5. Dexmedatomidine

Answer 142

1A. Onset - rapid onset due to partioning into lipophilic highly perfused tissues (brain, spinal cord)
B. Emergence - quick offset –> rapidly redistributes from highly perfused tissues into lean tissues; use context sensitive half time –> longer duration is more likely to be used for maintenance

2. Propofol “milk of amnesia” - GABA agonist, used for induction and maintenance; amnestic but non-analgesic
   - bp decreases, tidal volume/RR and minute volume decrease
   - antiemetic
3. Etomidate - GABA agonist, used for induction and short sedation, also non-analgesic
   - no change to HR, BP
   - respiratory depressant
   - emetogenic
4. Ketamine - NMDA receptor antagonist, analgesic
   - dissociative anesthesia with nystagmus –> unpleasant emergence, can reverse opioid tolerance
   - increase in HR, BP
   - no respiratory depression –> airway preserved
5. Dexmedatomidine - alpha 2 agonist, used for sedation or adjunct, analgesic
   - preserves respiratory drive
   - decrease in HR, BP
   - increased context sensitive half time

Question 143

CT: what shows up hyperdense vs hypodense

When do you use MRI vs CT?

MRI: what shows up as hyper vs hypointense

Answer 143

CT: X-rays, compare Hounsefield units HU
isodense - brain parenchyma (40 HU)
hyperdense - blood (60-100 HU), bone, calcification (1000 HU)
hypodense - air, fat (-100), edema, CSF (0 HU)

MRI: use electrical coil to disturb equilibrium – calculate energy protons give off when they align back with magnetic field
MRI used to characterize things better in the brain - to further evaluate things seen in head CT bc v sensitive and specific - good for subacute infarcts (use DWI), MS (use FLAIR - T2W where CSF is dark)
CT better for hemorrhage (use non-contrast), bone

MRI T1: hypointense - CSF and edema 
hyperintense - white matter, fat 
T2: hypointense - white matter
hyperintense - CSF and edema
can use contrast to produce hyperintensity in vessels, areas of BBB breakdown