MBB TOLO – Week 2

Lecture 10 – Cerebrovascular System

 Common carotid artery  external and internal carotid
o External = students love friendly otters so much
(superior thyroid, lingual, facial, occipital, superficial
temporal, maxillary (middle meningineal))
o Internal artery – ANTERIOR CIRCULATION
 Enters skull through carotid canal, passes
cavernous sinus, enters subarchnoid space
 Branches:
 1. Opthalmic artery – optic foramen into
orbit
 2. Posterior communicating artery –
joins proximal part of posterior cerebral
artery
 Terminal branches:
 1. Anterior cerebral artery – runs over
optic nerve to midline to join to the anterior communicating artery from posterior circulation –
over corpus collosum
Supplies medial parts of frontal and parietal lobes
 2. Middle cerebral artery – lateral fissure!
o Gives off lenticulostriate arteries (perpendicular) – supply striatum, internal capsule
o Ex of end vessels that are sole arterial supply to cerebral tissue
o Supplies most of lateral aspect of
cerebral hemisphere
 VERTROBASILAR SYSTEM – posterior circulation
o Vertebral arteries – piece dura and enter subarachnoid
space at foramen magnum level
 Branches:
 1. Anterior spinal artery
 2. Posterior spinal arteries – from vertebral arteries
or PICA
 3. Posterior inferior cerebellar artery (PICA) –
posterior cerebellar hemispheres
 Then unite at pontomedullary junction to create the
basilar artery
 Infarcation happens here a lot because there
is only thing supplying it
o Basilar artery – posterior fossa – is at the midline at basis
pontis
 Branches:
 1. Anterior inferior cerebellar artery – inferior
cerebellum
 2. Internal auditory artery/ labyrinthine artery – go
with CN8 to inner ear
 3. Superior cerebellar artery – dorsal cerebellar
hemisphere
 4.Pontine arteries – go to pons
 Terminal branches: two posterior cerebral arteries
 Goes around midbrain to supply medial occipital lobes, medial and inferior temporal lobes
 These are superior to tentorium cerebelli
 Vascular supply of cerebral cortex
o Anterior = Supplies trunk, and legs and foot of sensory and motor pre and postcentral gyrus
o Middle = Supplies arm, hand, face, tongue (rest of it)

 Arterial anastomoses
 o Pial anastomoses – ends anastomose with each other
o Go around arterial circle of willis – which goes around pituitary stalk
o Connections between internal and external carotid
 Ex: ophthalmic artery to maxillary artery and vertebral artery to occipital artery
o Watershed zone – borders between large arterial territories: would be ischemic if hypoperfusion
 However, since there are two supplies, is supplied from one type of ischemia (blockage from one
branch
 However, would be ischemic if entire brain is hypoperfused (if there was decreased pressure in internal
carotid)
 Venous system
o External venous system – veins in subarachnoid space which drain into the superior sagittal, cavernous, and
tranverse sinus – also form basal vein
o Internal venous system drains central core
o Great cerebral vein – 2 cm
o Many venous anastomoses and venous blood leaves by going to dural sinus through bridging veins
 If these bridging veins are destroyed, get subdural hematoma
o Dural venous sinus drain into jugular vein
 Lymphatics – in mouse, lymphatics line dural sinus and has fluid and immune cells from CSf to lymph nodes – not
clear if also in humans
 Spinal cord – from spinal and radicular arteries
o 1. Anterior spinal artery (70% spinal cord)– formed by paired branches of vertebral arteries
 Supplies ventral and lateral columns and all grey matter except dorsal horns
o 2. Posterior spinal artery – go from vertebral arteries or PICA
 Supplies dorsal columns and dorsal horns
o 3. Radicular arteries (off aorta)– basically most important for thoracic and lumber regions
 Largest radicular artery is artery of adamkiewicz (supplies T10-L3)
o Watershed is at T1-T4, and L1 in anterior, Posterior is T1-T4
 Cerebral blood flow and cerebral metabolic rate
o CBF = 20%, and gray matter is 4x flow to white matter – 750 cc/min or 50 cc / 100g/min
 No store energy so very dependent on circulation, lose consciousness in 10 seconds
 Little glycogen reserve – can last 2 minutes after occluded blood supply
 CBF is determined by and couples cerebral glucose and oxygen metabolism
o Depends on Cerebral perfusion pressure (CPP) – or pressure gradient = internal JVP – arterial P
o Cerebral arterial pressure is regulated by reflexes
 Baroreceptors in aortic arch and carotid sinus
 Basomotor neurons cause sympathetic excitation if arterial pressure go below 50-60 Hg because
baroreceptors no longer work
o Cerebral vascular resistance
 Autoregulation – responsible to adjust and maintain CBF
 1. Myogenic factor – contraction of smooth muscle in rxn to increased arterial pressure
 2. Metabolic factors (inc PCO2, dec pH, dec PO2)  vasodilation
 Neural regulation – sympathetic adrenergic innervation if there is severe hypertension
 Maybe NO
 Critical CBF values
o Ischemia = deficiency of blood due to decreased flow, infarct = area of cell death because local ischemia
o If CBF goes below 22cc/100g/min (critical CBF for function) – get altered consciousness
o If CBF go below 8 cc / 100 g/min (critical CBF for tissue viability) – Na+/K+ failure so acidosis so die
o If between 8-22, cells at risk for dying if not restored within hours
o ISCHEMIC PENUMBRA – place that is ded but not TOTALLY ded so can be saved
 CBF in pathology
o Chronic hypertension shifts myogenic autoregulation to right
o Cerebral insults (stroke, tumor, arrest, acidosis) – can lead to areas of passive bed with CBF varying with
MAP and no response to PCO2 or PO2
 If you do not have autoregulation, you need strict BP control and fixed head elevation
 Hypoxia and ischemia
o Most hypoxic injury is a part of cerebral ischemia
o Loss consciousness after 6-8 seconds, no corneal reflex (10-20 seconds), no breathing (40-90 sec)
 Maybe resuscitation after 4-10 minute delay okay
o Some regions are more vulnerable to other, neurons are most vulnerable and glial are intermediately
vulnerable and endothelial cells least vulnerable
o Hippocampus (CA1 and CA3), purkinje cell layer in cerebellum, and layer 3-5 of cerebral cortex are very
vulnerable because large number of glutamate receptors
Lecture 11 – CSF System
 Ventricles
o Thalamus and hypothalamus sits and surrounds the 3rd ventricle
o Cerebral Aqueduct is on the midline
o Behind the pons and cerebellum is the 4th ventricle
o Lateral and median aperture – go out into the subarachnoid space
o Flow: lateral horn  interventricular foramen  3rd ventricle  cerebral aqueduct  4th ventricle 
lateral/median aperature
 Subarachnoid space
o Arachnoid trabeculae keep subarachnoid space together
 Cistern – flows in subarachnoid space!!!
o Collection of spinal fluid inside the brain are ventricles, outside the brain but inside dura is cistern
 Cisterna magnum, Supersella cistern, Prepontine cistern
 Interpenduncular cistern – basically where they are all located
 Quadrigeminal cistern – in early herniation goes into tentorium notch and pushes the fluid out
 Hydrodynamics
o 140 cc (half soda can) – 30 cc in spine, make 500 cc per day
o Purpose of CSF : Mechanical and biochemical protection
 The blood brain barrier – 2 way barrier w/ capillary endothelial cells (tight junction)
o Diffusion: lipid solubility, size (smaller is better), charge (charged = screwed),
proteins (small), efflux (pumped back out)
 Phenytoin – bound to albumin so decreased uptake
o Transport: Aquaporins, glucose, AA, choline, BIRNG IT INN
 Blood –CSF barrier Choroid plexus
o Permeability – lipid and gases move freely
 Water, glucose, and large AA
o CSF Secretion – water follows active transport of Na, Cl, HCO3
 Absorption and formation of CSF
o Formation is at a constant rate, absorption, once CSF pressure goes above 70,
increases linearly
 CSF vs interstitial fluid (why is this important?)
o Slow acclimatization
o Spinal anesthetics stay in higher CSF concentrations, and affect superficial neural structures more
 Places without BBB – circumventricular organs
o Posterior pituitary
o Median hypothalamus – sleep wake schedule
o Area postrema - sense toxins and chemicals in blood
o Subfornical organ – recognize pyrogens – set temp
o Organ vasculosum of lamina terminalis – sense kidneys
to see if you need to change BP
 Lumbar puncture
o Conus medularis – spinal cord ends at L2
o Caudal equina = spinal nerves of the spinal cord
 Clinical considerations
o Hydrocephalus – water in brain
 3 types: non-communicating, communicating,
and ex vacuo. Non-communicating = Happens
if you have obstruction. Tumor can block
regions and you can see where it is depending
on ventricle size
 If you draw fluid at the bottom that is noncommunicating, then you mess with the pressure and it might
herniate
 Ex vacuo – not enough brain, (maybe from aging, or stroke) – ventricles would just be large because
more space – fluid replaces brain
o Low pressure
 Positional headache, provoked, spontaneous
  If you stand, CSF does not hold your head and so it hurts your head
 Bypassing BBB – intrathecal medications bypass the BBB
o Tight junctions breakdown in CNS injury
o Cerebral edema –
o Extra penetration of drug – antibiotics and morphine can cross better if there is already damage so you might
have to adjust medication in these cases
 Drugs:
o Vasogenic edema – glucosteroids and osmotic agents (mannitol and dexmethascone)
o CSF production
 Acetozolamide – CSF production requires secretion of HCO3 into CSF by choroid plexus and since
acetazolamide inhibits this, it can reduce CSF production
 Furosemide – inhibiting transport so reduces CSF production
Lecture 12 – Peripheral Nervous System and Motor System: The Motor Unit
 The spinal segment
o Roots, Dorsal Root Ganglion, Spinal Nerve
 Specify Spinal segment or the bone, because these are different
 IS the DRG at the same level of the spinal segment or bone?
o Peripheral NS ends right when the axon leaves the spinal cord specifically – when it becomes ventral root
o Spinal nerve = the dorsal root and ventral root come together
o Once you pass the spine bone – you see the sympathetic chain ganglion
 The two connections are called the communicating ramus, the grey ramus and white
 White connects preganglionic sympathetic fibers from spinal nerve  sympathetic ganglia
 Gray – carry sympathetic ganglia to spinal nerves
o Then it divides into the dorsal ramus (motor fibers around spinal bones, and sensory from around spine) and
ventral ramus, which goes to brachial plexus, or other places
 Dermatones and myotones
o Dermatone – skin that is supplied by a spinal nerve
o Myotome – group of muscles supplied by a single root
 Muscle and skin overlying it can be innervated by other things
 Do not confuse the dermatone from peripheral nerves. If there is something wrong, think about if it is
a specific spinal segment that is broken, or the same peripheral nerve
o Blurrer borders – there is overlap between the sensory segments – because they overlap
 But from the Peripheral nerve patterns – it is very specific. So if patient can specify where it is, it
might be a peripheral nerve. If it is vague, then it is probably a spinal nerve because those are unclear
 Different pathways – motor and sensory
o Somatic motor pathway – Movement of voluntary body
 Cell body in bottom of ventral body (Lower motor neuron) – sent its axon out and runs into the
ventral nerve and goes into the plexus, and go through plexus and go to the musculocutaneous nerve
o Visceral motor pathway- autonomic fiber
 Come from middle of ventral body – comes out of ventral root, and goes through white ramus then
travels along the chain ganglia and exists and goes out the ventral root where it wants to
o Somatic sensory – pain and temp/proprioception and discriminating touch + Visceral sensory (internal body is
my cecum full)
 Axon is in the periphery which comes the peripheral nerve, comes to the dorsal root, to DRG, and
goes into the dorsal horn
 Histology of the PNS
o Axon is inside schwann cell for myelin, lots of axons wrapped by endoneurium, and wrapped in perineurium
which is a fascicle. Multiple fascicles and blood vessels are wrapped into an epineurium
o Fiber classifications
 Bigger fiber is, the more myelination there is, and goes faster
 A-Alpha – Ia- is larger because it is LMN! And so it has to go fast and go really far distances
 A-alpha – Ib- golgi, touch – get sense back for touch
 B – slow autonomic pain – don’t put your hand on it, use a slow fiber this entire time and it is vague
amount of time
 If you have a disease that effects peripheral myelin, it might affect LMN. If something targets small
neurons, then your pain might be bad
 The motor unit = one lower motor neuron and the muscles that are innervated by it
o One motor neuron can control multiple muscle fibers
 Neuromuscular Junction
o Endoneurium becomes endomysium and forms the synapse
o The NT Ach is released and receptors for muscle contraction
 Muscle
o Fibers  Fasculi  Muscle
o Interfusal fibers/spindles – inside the muscle – sensory organ to give information about the contractile state
of the muscle – fast myelinated neurons
o Functional classification – flexor, extensor, orgin, insertion, perimysium (outside of the muscle becomes
tendon to cross the joint
o Muscle – signal from nerve leaves to fiber twitch and lysis ATP to shorten the muscle
  When enough fibers fire, you can get tetanic contraction
 Some muscles have high endurance – lots of oxidative metabolism and slow contraction time for
recharge (birbs who fly)
 Strongest – lots of fibers, able to twitch quickly but not that many times. (white meat)
 Weakness = failure to contract the muscle fiber
o Loss of strength = paralysis, paresis, palsy
o Could be – UMN, LMN, NMJ, Muscle
o Plegia = mono, hemi, tetra, para
 Mono plegia = weakness of one limb
 Hemiplegia = weakness of one half of the body
 Tetraplegia = all four limbs (bilateral brain injury)
 Paraplegia = both legs
 Lower motor neuron lesion
o Weakness, hypotonia, decreased stretch reflexes, atrophy, fasciculations
 The neuron gives trophic factors
 Muscle does stuff by itself so that’s why you get intermittent fasciculation
o Mixed or not?
 Pure motor neurons cell body disorders would only have motor dysfunction
 Disorders in plexi produces mixed motor and sensory systems
 Peripheral Nerve disorders – in the Axon
o Neuropathy
 Mono, multiple mono, poly (some selective vulnerable of all the nerves)
 Mononeuropathy – signs and symptoms are in one nerve
 Shingles or carpal tunnel
 Polyneuropathy – affects all similar peripheral nerve in the same fashion – stocking glove, diabetes
o Negative symptoms – weakness, loss of sensation
o Positive symptoms – fasciculations, cramps, pain, abnormal sensation
 Other diseases
o Disorders of neuromuscular junction
 Not enough NT, not enough released, blocked binding sites, failure to metabolize NT, insufficient
muscle response
o Myopathy – primary disease of muscle
 Usually proximal, and symmetric pseudohypertrophy (replace with fat and fibers), and mostly
painless
 Duchenne Muscular Dysrophy – pseudohypertrophy is common in these patients
 Studies to confirm
o Electromyography and Nerve conduction Velocity studies (EMG/NCV)
o Help distinguish between muscle problem, LMN problem, NMJ problem
 How to treat
o Supportive treatment – education and protection
o Sympatomatic treatment – pain control, rehab
o Restorative / curative treatment – surgical repairs and medical treatments
 Can split a nerve and put it onto two different muscles
Lecture 13 – Motor System: reflex and conscious control of LMN
 REFLEX
o Receptor afferent (I just got stretched) synapse  effector (LMN)  effective
 You need to have an adequate stimulus to start
 Terms:
 Mono-,di-,poly- synaptic
 Ipsi-, contra-lateral (same side response or other side)
 Synergist – muscles that are working in the same direction – like all the extensors
 Antagonist – flexor vs extensors
 Spinal cord reflex
o Hard wire to facilitate movement
o Maintains muscle length constant
o Monosynaptic reflex
 Spindle – intrafusal fibers- contractile striated ends, sensory organ in
the middle, between muscle fibers
o 1a and 1l sensory afferents, gamma motor efferents
o Function – parallel to muscle fibers and discharge increase with stretch
o Gamma efferents kept taught
o If the spindle gets slack, then it stops firing, and the other part of the spindle will contract backward to reset it to
the tonic position
 Golgi tendon reflexes – disynaptic reflex – excites an inhibitory interneuron that inhibits the alpha-motor neuron
o Golgi tendon organ = receptor
o If the muscle is too stretched, it activates the interneuron to prevent injury from overstretching
 Reciprocal Innervation
o For any movement, you have to excite agonist and inhibit antagonist
o Sidynaptic innervation – with the glycinergic interneuron from the golgi reflex
o So it contract the quadriceps, and turns off the hamstrings
 Automated, polysynaptic reflexes
o If you painfully hurt your foot, your L2 – ilopsoas contract and quads
contract to get your foot away, and then the contralateral quads extend to
support your body
o If someone has a really bad injury to brain, this reflex still happens, or is
hyperreflex
 All reflexes, whose running the show?
o Brain steam control
 Face and eye reflexes (cornea- close your eye)
 Vestibular reflexes
o Descending extrapyramidal pathways
 Reticulospinal – retricular formation going to spinal cord –
awake vs asleep
 Descending MLF – vestibular sense to eye to spinal cord – so
you can stay on target when you are focusing on something
 Tectospinal – prepare the muscles for getting up
o Cortical and descending pyramidal system
 Upper motor neuron – control the LMN
 Tracts
o Descending pyramidal / corticospinal – from brain to limb
o Go from the coronol radiala – and go through white matter called
posterior limb of the internal capsule  Crus Cerebri  basis pontis 
medullary pyramid  cross at bottom of pyramid (pyramidal decussation)
 This is where the brain stops and spinal cord starts
 Crus cerebri and basis pontis has all the descending fibers
 Some fibers do not cross over (decussate) but not as important
or noticeable if broken

 UMN Lesions
 o Patterns of weakness
 ARM and wrist wants to stay contracted and the leg wants to stay extended
o Spasticity – natural resting tone is too high and you get clonus – LMN wants to keep limb very stiff
 Can hurt because you are overstretching it so the golgi stretch sensory is activated but cant fix it
o Increased stretch reflexes – very brisk
o Babinkski sign – triple flexion – these natural reflexes that are normally turned off
in the brain
 When you are born, corticospinal tract is not myelinated
 Triple flexion – sometimes your foot flexes up when you are trying to
walk
o At the initial damage of the weakness, flaccidity and hyporeflexia – will look like
LMN lesion but over hours – day, then you will have normal reactions
o Decorticate posturing – disinhibition of pontine reticulospinal tract so look like a
dog – really bad because you see that cortical areas are just doing whatever they
want and brainstem functions are not normal
 Damage to lateral corticospinal tract, and disinhibition of red nucleus
o Decerebrate posturing – disinhibition of vestibulospinal reflexes
 Brainstem damage below the red nucleus
 Lower motor neuron lesion
o Atrophy and fasciculations
o Hypotonia
o Weakness
o Hyporeflexia
o No pathologic reflexes
 Treatments
o Education, prosthetics, rehabilitations
o Hypertronicity – Rigidity/ Spasticity – regulate the spasticity? Reduce pain or resistance to limb
o Muscle spasm – can we stop
o Fatigue/weakness – can we help this
 Anti-spasticity medication
o Baclofen – Gaba B agonist on the muscle to decrease the signals
 Or presynaptic side to decrease NT
 So patient will become weaker because theres less signals
 So maybe interthecal administration so it goes directly to the lumbar spine for your limbs / local
targets
o Can also use Gaba A agonist – benzodiazepines (but not as good because also sedative)
o Tizandine – A2 agonist presynaptic which inhibits NT release
o Dantrolene – muscle relaxant at the level of the muscle by decrease Ca influx
 Best for acute muscle spasm cause by injury – relax so you can sleep at night
 Probably has to do with sedation in the brainstem
o BoTox – interfere with the NMJ to relax but at least you can clean the hand
 Fatigue medications
o Stimulants
o Amantadine (symmetrel) – anti parksinsonism effect
Lecture 14 / 15- Motor System: Basal Ganglia, and Movement Disorders and Drugs
 The basal ganglia – collection of subcortical nuclei or extrapyramidal motor system
o Striatum – caudate and putamen (connected)
o Pallidum – globus pallidus (interna and externa)
 Lenticular nuclei – putamen and globus pallidus together
 Anatomy
o 7. Thalamus
 Lateral to the third ventricle = thalamus
o 4. Putamen
o 1 (head), 2 (body), 3(tail), 6 – Caudate
 Caudate head is always lateral to the lateral ventricle
 Circuitry
o Input Nuclei (striatum)
 Caudate – saccadic eye movement, cognitive movements
 Putamen – mostly motor control
o Output Nuclei
 Globus Pallidus Interna
 Substantia Nigra Pas Reticulata
o Two circuits: Excitatory (more movements, larger, faster) and Inhibitory (less
movements, less, slower)

 Excitatory – putamen inhibits the output nuclei, which normally inhibit
the thalamus
 Inhibitory – putamen inhibits through GPe and STN less well so the
output nuclei is super strong and inhibits the thalamus
 Because GABA is everywhere, it is hard to use GABA drugs to be super
helpful
o Dopamine Projections
 Substantia Nigra – Increase the excitatory pathway and decreases the
inhibitory pathway
 Use dopamine
o Acetylcholine Projection
 From Striatum which decreases normal movement in general
 Lesions
o Hypokinetic (too few movements – lesion excitatory putamen, GP, or Substantia
Nigra)
 Akinesia/Bradykinesia- inability to start movements / slowness of the movement itself
 Are not weak because no muscle, NMJ, or LMN or UMN problem
 Rigidity – tone is increased because of basal ganglia movement disorder
 Stooped Posture – continuously not upright
 Retropulsion – cannot pick up foot quickly when moving forward or backward so have to take extra
steps and move faster – test by dragging them back and if they take more than 3 steps to catch
themselves then they have it
o Hyperkinetic – STN, Inhibitory putamen
 Chorea (movement that does not belong)
 1. Ballismus – quick large flinging movements
 2. Athetosis – finger writhing
 3. Dyskinesis – movements that bad
 Tic – exact same movement every single time
 Dystonia – look still but is tonically hyperkinetic and something is always contracting
 Tremor (Parkinson / essential) - Movement that does not belong
 Possible in hypokinetic and hyperkinetic disorders
 Akisthesis – ants in your pants – cannot sit still and have to move
 Restless leg syndrome – limbs feel better if they are in motion
 Treatment – type of abnormal movement, reason, include supportive care, education, therapy
o Parkinsonism due to SNc- clinical phenotype
 Resting tremor, rigidity, akinesia/bradykinesia/failure of righting gait
 Increase dopaminergic tone
o Parkinsonism due to putamen or globus pallidus – much harder to fix
 Use cholinergic antagonists
o Putamen – hyperkinetic movements
 As degeneration starts, hyperkinetic movements start first and then lead
to hypokinetic movements
o Caudate – psychiatric symptoms, cognitive deficits and problems with how eyes
move
 Drugs for Parkinsonism
o Treat too few movements
 Bradkinesia, rigidity, failure of postural righting reflexes
 Also can treat unpredicted tumors
o Levodopa and Carbidopa  dopamine in CNS
 Carbidopa blocks peripheral metabolism in GI – so no nausea and
vomiting
 Side effects = hallucinations, GI hypermotility, autonomic instability,
dyskinesias (extra movements)
 If patient is older and has more severe disease, then maybe use this drug because its life span is 5
years
 If patient is younger and does not need to move quickly, maybe use other drugs first
o COMT inhibitors – Entacapone
 Inhibits L-Dopa conversion peripherally, and combine it with carbidopa/levodopa
 If it penetrates the BBB, then it can inhibit dopamine breakdown but we do not have legal
drug here
o Dopamine agonist - Ropinirole – less effective but fewer long term dyskinesias
 Sleepiness, impulse control disorders (like gambling more)
o Muscarinic anticholinergics – Trihexyphenidyl – has a lot of side effects
 Dry mouth, urinary retention, mydriasis, sedation, confusion
 Not as useful – adjunct for tremor for younger patients
o MAO-B Inhibitors – Selegiline
 Small effect and extend duration of action of other drugs
(carbodopa/levodopa)
 Do not use with meperidine SSRI/TCA for fear of serotonin syndrome
o NMDA Receptor Antagonist - Amantadine
 May be dopamine synthesis and release potentiator – can be helpful for tremor or fatigue
 Risk of confusion, nausea, hallucination, and livedo reticularis
 Drugs for chorea
o VMAT2 Antagonism – stop from having hyperkinetic movements
 Vesicle monoamine transporter 2 – allows dopamine into presynaptic vesicles
 Methamphetamines block VMAT2 in addition to reversing dopamine reuptake
 Tetrabenazine – decreases movements
 Side effects: hypotension, depression, sedation, Parksonism
o Antipsychotics – blocking dopamine
 Haloperidol – 1st gen antipsychotic, D2 antagonist, might get Parkinsonism, hyperprolactinemia and
tardive dyskinesia – initially, decrease movements but then the receptors probably overexpress
themselves so they you get dyskinesias
 Olanzapine – 2ND gen – less parksinonism – so not as effective in decreasing movements
 Drugs for Tics
o Can use antipsychotics
o VMAT2 antagonist
o Alpha2 receptor agonist
o Clonidine – decreased activity of locus ceruleus neruons
o Botox – block acetylcholine vesicle fusion and release in presynaptic
 Drugs with essential tremors
o Tremors only when active, not a resting tremor
o Propanol – blockage of sympathetic activity
 Good CNS penetration due to lipid solubility
 Nonselective, so cannot use it in athletes and aerobic
 Depression? Not actually, Nocebo – side effect not really established
o GABAa transmissions
 Alcohol helps with essential tremors
 Only okay for limited social situations
 Primidone – barbiturates – long acting but sedation
 Topiramate – blocks Na channels and carbonic anhydrase - acidosis
 Gabapentin – VGCa channels, ataxis, no metabolism
 Benzodiazepines – cognitive slowing, abuse
 Drugs for dystonia
o Botox – for focal dystonia
Lecture 16 – Cerebellum
 Cerebellar Anatomy
o Vermis – midline – keep torso balanced when standing
o Hemispheres – Ipsilateral!!
o Tonsils
o Folium – molecular, purkinje, granular
 Purkinje die if you get hypoxia
o Deep nuclei
 1. Fastigial
 2. Globose
 3. Emboliform
 4. Dentate
o Cerebellar Peduncles – superior, middle, inferior – attach to pons
 Cerebellar Circuitry
o Smooth, coordinate, input from spinal cord about movements in progress – make it from target 1 to target 2
o Inputs: limb information from spinal cord to tell it where it is
 1st tract - Spinocerebellar tract – actions that are already moving
 Information from golgi tendon organs and muscle spindles
 Sensory information  DRG and synapse in ventral horn (clark’s nucleus) and ascends
ipsilaterally and goes through the inferior cerebellar peduncle
 There is also a stupid one that crosses, and goes up through SCP and then crosses back again
 2nd tract – corticopontocerebellar pathway useful for movements too fast to be smoothed in progress
 Outer and inner crus cerebri  pons  ducussate  lower nucleus
 Motor and sensory cortex  contralateral pons  Middle cerebellar peduncle  cerebellar
cortex  dentate nucleus  SCP  to thalamus  back to primary motor cortex 
corticospinal tract
o Output through dentate nucleus = dentatorubrothalamic tract from
cerebellum to the cerebral hemisphere through superior peduncle
 superior cerebellar peduncle  contralateral midbrain 
thalamic nucleus VL  primary motor cortex
o Information comes in through DRG, go through synapses in spinal cord or
in the medulla
 There is also another pathway through DRG, go to anterior horn,
synapses, and decussates, and goes up through SCP and
decussates again
o The pathway to learning new motor skills is different than learning words
 Cerebellar lesions
o Unsmooth, uncoordinated, ataxia, hypotonic
o Vermal
 Truncal Ataxia – cannot make trunk smoothly stay where its supposed to be
 Widened stance, drunken gait
o Dysarthria (speech)
o Hemispheric
 Ipsilateral ataxia – left hemisphere - right anterior limb lesion, or left cerebellar lesion
 Extremities, dysmetria, adiadochokinesia, intention tremor (finger missing and trying to
correct it)
o Nuclear – dentate nucleus – get input from both input and output pathways
 Cortex cerebellum deficit is okay, nuclei deficit, not okay
o Corticoponto lesions -
o Cord lesions – usually have to lesion both sides of the cord because there is more than one tract for
spinocerebellar
 Look like vermis problem as well
o Therapy, education, support and adaptation, rarely surgery and no medical therapy
Lecture 17: Somatosensory system
 Transduction – sensory stimuli  AP
o Receptors:
 Exteroceptors (sensor that senses something outside – pain, heat)
 Proprioceptors (position of your limb)
 Interoceptors (internal part of your body – how much your colon/bladder is stretched)
o Stimulus needs to reach the threshold amount
 Somatosensation
o 1st order cells is in a ganglion leaves the PNS (most of them in DRG) and enters into CNS
o 2nd order cell in CNS crosses and synapses in the thalamus
o 3rd order cell in thalamus projects to cortex
o 2 primary pathways:
 1. Dorsal column / Medial Lemniscus (once in the brain)
 Joint position sense (conscious proprioception)
 Discriminative touch – you touched me here, this long, with this thing
 Large myelinated and encapsulated (special sensory organs)
 The legs are in fasciculus gracilus and the arms are in fasciculus cunneatus
 2. Spinothalamic
 Crude touch – something touched me on my forearm, I don’t know where or how much but I
just know that it did
 Pain
 Temperature
 Free Nerves is conduction element
 Small unmyelinated

 o Caveats
 Fast pain straight to thalamus
 Slow pain to reticular formations
 Pain has built in unpleasantness (unlike temperature)
o If you have a tumor in the ependymal cells, then it will hit the
cervical places first so you will get sacral sparring
 Trigeminal system – add in the face sensation
o One trigeminal ganglion from V1, V2, V3 – one pool with
discriminate touch, one for pain
 Discriminate touch - Pontine trigeminal nucleus
 Pain – descend on spinal tract of the trigeminal nerve
and synapses on spinal nucleus of the trigeminal nerve in caudal medulla and projects up in the
trigeminalthalamic tract up
 Somatosensory cortex
o Primary is in the precentral gyrus, but there is also secondary somatosensory cortex near the temporal lobe
near the thalamus (inferior/posterior lateral sulcus)
 SI = discriminative sensation and pain, SII – has aware of pain and crude touch
o If you injure thalamus, totally no sensations, but if you injure primary map, you still have crude in the S-II
 Clinical Terms
o Numbness
o Anesthesia = lack of sensation and pain
o Analgesia = no pain but can still feel
o Dysesthesia – touch but interrepted it wrong, discomfort/pain from normal stimuli touch
o Paresthesia – extra feeling – burning or prickling sensation
 Localization
o Light touch – anywhere – usually need both system out
o Pin and temperature
 Small fiber PNS, spinothalamic system
o Joint position sense, two point discrimination,
tactile localization, graphesthesia (draw number
in palm), stereognosis ( put something in ur
hand and you tell me what it is)
 Large fiber PNS, Dorsal Column
System
o Vibration – partially screwed up by either tract
so less valuable
o Commisural syndrome – white commissure –
substantia gelanosa have to cross over
 Visceral Referred Pain
o Some organs do not have receptors so they
refer to somewhere else
18 Mechanisms of Pain
 Terminology for pain
o Pain
 Acute high intensity stimuli – crab pinches your nose
 Pain correlates with intensity, pain stops when stimulus stops and pain is localized to stimuli
 Tissue injury and inflammation
 Pain producing agents (damaged tissue, inflammatory cells, mast cells, antidromic signal)
o Antidromic signal – sensory signals go down and reactivate more pain receptors
which then send more pain back up
 Central spinal sensitization – when you get lots of pain, your spinal cord is more sensitive and
looks for pain signaling more
 Neuropathic pain – nerve being injured
 Persistent or paroxysmal- Lancinating (sharp paraoxysmal)
 Hyperalgesia, Allodynia, autonomic dysfunction
 Pathophysiology
 Injuries lead to
o Traumatic neuromas
o Ectopic Signaling – false signaling (pain signal next to touch signal and when you
touch, the pain also gets it too)
o Mechanosensity due to demyelination
 Tinel’s - testing for carpal tunnel by pressing on the median nerve
 Lhermitte’s – bend neck and shoots pain when demyelination in spinal cord
 Crosstalk
o Thalamic lesions or phantom pain – sensory cortex without thalamic stimuli will
develop pain stimulus in region that is missing
o Hyperalgesia – more painful than you would have normally, sunburn + hot water
o Allodynia – light touch provoke pain
 Contributions to spinothalamic tract
o Adelta – faster pain
o C – slower pain
 Both go through SG and then through to spinal thalamic
tract
o A-beta – do touch , but also go to Wide dynamic range neurons
(which is right underneath SG), which goes through
spinothalamic tract as well
 Can regulate the SG a little so that’s why touching
decreases pain
 Pain transmission and modulation
o Peripheral
 If you injury the peripheral terminus – you get pain stimulus. But if this injury is long enough, there is
cytokines, and phosphorylation and prostaglandins so more pain in the periphery
 Capsaicin also has receptors to increase pain as well
o Spinal Cord – through the WD neurons
 Interneurons for GABA and glycinergic decrease WD
neurons to tell them to stop
 COX signaling increase SG and WD, and inhibit glycinergic
neurons so overall, increase pain double whammy
 WD also has NMDA receptor for C pain fibers
o Brainstem
 Serotonergic Raphe nuclei – inhibitory and excitatory are
both involved in pain so cannot use SSRI
 Locus cereleus and lateral pontine tegmentum – NE decreases
pain
 Opoid receptors decrease pain transmission - also in
periaquductal grey– running high
Chapter 19 - Drugs
 Overview
o Analgesics – elevated pain threshold, and reduce hyperalgesia/allodynia
o Neuropathic pain drugs – separate group – not analgesic
o Some drugs are very potent and some are not
 Representative classes
o COX inhibitors / Acetaminophen – helps with tissue injury and inflammation
o Morphine – opoid-u agonist – analgesia for acute high intensity and long term pain for tissue injury and
inflammation, and injury of NS
o Gabapentin and amitriptyline – NET/SERT inhibitors – tissue injury and inflammation, and nerve pain
 NSAIDs
o Drugs: Ibuprofen (advil, motrin), Celecoxib (Celebrex), acetaminophen (Tylenol)
 Inhibition of COX
 COX1 in CNS and periphery
 COX2 in spinal cord - in double whammy
 Probably not mechanism for acetaminophen
 Adverse effects
 Tylenol – liver toxicity
 Other NSAIDS – abdominal pain, bleeding, renal failure, interact with aspirin