Supplemental Material

Nervous System I
Where’s the lesion?
Lower Motor Neuron Upper Motor Neuron
 Upper Motor Neuron vs. Lower Motor Neuron

LOWER MOTOR NEURON UPPER MOTOR NEURON

Site Anywhere from Anterior Horn Brain
Cell to Muscle Spinal Cord
Distribution Segmental (number) Diffuse or patchy
Reflexes Absent or Reduced Exaggerated
Babinski absent Babinski present
Strength Decreased Decreased
Tone Decreased Increased, clonus
Atrophy Severe Mild, not prominent
Fasciculations Present Not Present
Paralysis
Type Flaccid Spastic and Rigid
Location Paresis limited to specific Contralateral hemiparesis
muscles
Pattern of Weakness Depends on site of lesion Extensors in arms
Flexors in legs
 Spinal Cord Pathways
Ascending Pathways Function Location Clinical Correlate
Dorsal Column Proprioception, Ascends ipsilateral and Laterality of the
vibration, fine crosses in the medulla; deficit depends on
(discriminative) touch becomes medial lemniscus level of the lesion:
to Ventral Posterolateral ipsilateral in the
Gracile fasciculus Lower body (VPL) thalamus to spinal cord, but
Somatosensory Cortex contralateral in the
Cuneate fasciculus Upper body brain stem and
above
Spinothalamic Pain, temperature, Crosses within 1-2 Interruption
crude (light) touch segments upon entry and produces loss of pain
ascends contralaterally to and temperature on
Ventral Posterolateral the opposite side of
(VPL) thalamus to the body
Somatosensory Cortex
Spinocerebellar Cell body in nucleus
dorsalis Ipsilateral loss of
Posterior Proprioception Ascends ipsilateral to the information
(dorsal) information from the vermis of the cerebellum regarding the
leg constant and
changing lengths of
muscle and tension
on muscles =
incoordination.

Ipsi- and/or
Anterior Joint and position Crosses at the level of the contralateral loss of
(ventral) information spinal cord. Ascends to coordination and
enter cerebellum and balance
recrosses before ending in
the vermis (ultimately ends
ipsilateral to side of origin)
Main Trigeminal Discriminative touch, Trigeminal ganglion to A lesion of the
Sensory vibration of head and main sensory nucleus in medial lemniscus
neck rostral pons, crosses and above the mid-pons
ascends to VPM thalamus will involve all
in the ventral trigeminal
trigeminothalamic tract; sensations on the
uncrossed fibers ascend in contralateral side
the dorsal
trigeminothalamic tract to
somatosensory cortex
Spinal Trigeminal Pain, temperature of Enter from trigeminal Lesion in the
head and neck ganglion and descend to medulla or higher
spinal trigeminal nucleus. cervical cord causes
Spinal trigeminal axons ipsilateral loss of
 cross and ascend to ventral
medial lateral (VPM)
thalamus to
somatosensory cortex
Descending Pathways Function Location
Corticospinal Voluntary motor Cell body in Motor Cortex
Lateral Crossed Crosses in the medulla and
descends
Anterior Uncrossed Descends without crossing
Rubrospinal Control of tone in Originates in red nucleus,
flexor muscle groups crosses just below the
(facilitates flexors, nucleus and descends in
inhibits extensors) the tegmentum of the
brain stem and lateral
funiculus of the spinal
cord.
pain and
temperature of the
face
Clinical Correlate
Interruption above
foramen magnum
results in
contralateral deficit;
lesion in the spinal
cord causes
ipsilateral loss of
function
Hard to get a lesion
only of this nucleus;
likely results in
motor problems of
the contralateral
limbs.

Vestibulospinal
Lateral Facilitative influence; Originates in lateral Lesion of CN VIII,
vestibular system vestibular nucleus, lateral vestibular
brings about postural descends in tegmentum of nucleus or
changes to the brain stem and ventral semicircular canals
compensate for tilts funiculus of spinal cord; causes a patient to
and movements of ipsilateral fall to side of lesion
the body while walking; lesion
to tract in the spinal
cord is generally
masked by more
severe motor
deficits resulting
from concomitant
injury to the lateral
corticospinal tract.

Medial Stabilizes head Originates in medial Lesion leads to

position as we walk vestibular nucleus and impaired vestibulo-
around projects bilaterally to ocular reflexes and
cervical spinal cord eye coordination
Reticulospinal It is impossible to
Pontine (medial) Excitatory: Maintains Descends in tegmentum of transect the
postural muscle tone brain stem and ventral reticulospinal tracts
and direct voluntary funiculus of spinal cord – without involving
movement by does not cross the other tracts.
 enhancing antigravity Lesions cause
reflexes (facilitates deficient postural
upper limb flexors reactions and
and lower limb interfere with gait
extensors. generation.

Medullary Descends in ventral part of

Inhibitory: Maintains lateral funiculus – some
postural muscle tone cross in the medulla
and direct voluntary
movement by
reducing antigravity
reflexes of the spinal
cord.
Tectospinal Orients head or eyes From superior colliculus, Impaired visual and
to visual or auditory crosses in the dorsal auditory reflexes;
stimuli tegmentum and descends inability to move
to anterior funiculus of head
spinal cord.
 Diagnostic Testing for Neuromuscular Disease
AchR Antibody Test = Acetylcholine receptor antibody = positive in Myasthenia Gravis
Voltage-gated Calcium Channel antibody test = positive in LEMS (Lambert Eaton
Myasthenic Syndrome)
MUSK Antibody Test = MUSK is a muscle-specific a tyrosine kinase receptor which is required
for the formation of the neuromuscular junction. The presence of quantitative antibodies to
(MuSK) suggest the diagnosis of MG
SMN DNA Testing = 95% of individuals affected with Spinal Muscular Atrophy will have a
homozygous deletion of SMN1. Defects in Survival Motor Neuron 1 (SMN1). SMN2 gene could
compensate but exon 7 typically excised, resulting in low protein levels
SS-A/Ro and SS-B/La Antibodies – useful for evaluating patients with signs and symptoms of
a connective tissue disease in whom the test for antinuclear antibodies is positive such as in
Sjogren syndrome and lupus.
PAVAL: Paraneoplastic Autoantibody Evaluation = Serological evaluation of patients who
present with a subacute neurological disorder of undetermined etiology, especially those with
known risk factors for cancer
Anti-Jo-1 autoantibodies in sera of patients with polymyositis.
Anti-Mi-2 autoantibodies in sera of patients with dermatomyositis.
PMP22 duplication/mutation - CMT1A (Charcot-Marie-Tooth Disease Type 1A)

PMP22 deletion – HNPP (Hereditary Neuropathy with Liability to Pressure Palsies)

Connexin 32 mutation; GJβ1 mutations – CMTX (Charcot-Marie-Tooth Disease Type X)

GDAP1 defective gene - CMT4A - (Charcot-Marie-Tooth Disease Type 4A)

Dystrophin DNA Testing

• Duchene Muscular Dystrophy - Over 1,000 known mutations that cause DMD, often
deletions or duplications within the gene, leading to non-functional protein
• Becker Muscular Dystrophy - Exon skipping that leads to shortened protein that
retains at least partial function

Triplet repeat expansion

• Myotonic dystrophy - type 1 is caused by CTG repeat expansion in the 3’ non-
coding region of the DMPK gene
• Friedreich’s ataxia - GAA repeat expansion in intron 1 of the Frataxin gene
• ALS - C9ORF72 repeat expansion in intron 1 is the most common genetic cause
of ALS
Myotubularin (MTM1) gene mutation –Centronuclear/Myotubular Myopathy
α-Actin mutation - Nemaline (rod) Myopathy
CLCN1 gene mutation – mutation in chloride channel, chr 7= Myotonia congenital,
Autosomal recessive (Becker-type), autosomal dominant (Thomsen's)
Chromosome 4q35 deletion - Facioscapulohumeral muscular dystrophy
Mitochondrial Myopathies
• mtDNA:
– MERRF (tRNA Lys)
– MELAS (tRNA Leu)
– Kerns-Sayer Syndrome (mtDNA deletions)
• Nuclear DNA
– Progressive External Ophthalmoplegia (POLG1)
– Mitochondrial neurogastrointestinal encephalomyopathy (TYMP)

Serum Creatine phosphokinase MM isoenzyme (specific for skeletal muscle) –

elevated in muscle necrosis
Serum Aldolase – Elevated levels found in progressive Duchene muscular dystrophy;
Elevations also occur in carriers of MD, in limb-girdle dystrophy and other dystrophies,
in dermatomyositis, polymyositis, and trichinosis
Serum Lactate Dehydrogenase-5 (LDH-5) – Elevated in muscle necrosis
Brain stem Structures to Know and Love

At each level of the brain stem (medulla, pons, and midbrain), clinical diagnosis of neurological
dysfunction requires a good working knowledge of what functions are performed by nuclei or
tracts at each level.

Medulla

Dorsal column/medial lemniscus system

-The spinal cord fibers of the dorsal column
fibers of the fasciculus gracilis and fasciculus
cuneatus terminate on the cells of the nucleus
gracilis and nucleus cuneatus.

-Cells of the nucleus gracilis and nucleus

cuneatus send axons across the midline to
ascend as the medial lemniscus. Each medial
lemniscus is found adjacent to the midline in
the medulla.

Anterolateral System
The fibers of the anterolateral system
(spinothalamic fibers) pass rostral ward from
the spinal cord and assume a lateral position in
the medulla.

Pyramidal Motor System

-The corticospinal fibers of the pyramidal
motor system are located in the ventral
(anterior) medulla as the pyramids.

-At the caudal end of the medulla, 85% of the

fibers cross the midline in the pyramidal
decussation to form the lateral corticospinal
tract in the spinal cord.

The important cranial nerve structures of

the medulla are the
Hypoglossal nucleus;

Nucleus ambiguous; and

Spinal tract and nucleus of V.

Relative to autonomic function, these nuclei are significant:

Dorsal motor nucleus of the vagus is a collection of preganglionic, parasympathetic neurons; and

Nucleus of the solitary tract receives important visceral afferents (including the special visceral
afferent of taste).

The following are important relative to cerebellar function:

The inferior olivary nucleus is interconnected to the cerebellum and is crucial to cerebellar
function.

The inferior cerebellar peduncle is composed of axons interconnection medullary structures with
the cerebellum.

Pons
Long tracts
The medial lemniscus continues rostrally, although it begins to rotate and move laterally away
from the midline.

The spinothalamic fibers continue in the lateral tegmentum of the pons.

The pyramidal tract fibers pass caudally in the base of the pons.

Base of the Pons

The base of the pons is composed of three neural groups: corticopontine fibers, pontine nuclei
and their axons (pontocerebellar fibers). The descending corticospinal fibers pass caudally
through the base of the pons.

The middle cerebellar peduncle is composed of the huge accumulation of pontocerebellar fibers.

Pons and Medulla

Several important structures are located at boundary of the medulla and the pons.

Vestibular nuclei receive input from the vestibular apparatus and are interconnected to the
cerebellum. The lateral vestibular nucleus sends axons into the spinal cord.

Cochlear nuclei receive axons of CN VIII from the cochlea. Cells of the cochlear nuclei send
axons to more rostral components of the auditory pathway.

Midbrain
Tectum
The tectum is composed of a pair of superior colliculi and a pair of inferior colliculi.

The superior colliculi are important for visual reflexes involved in eye movements.

The inferior colliculi are components of the auditory pathways.

The pretectum is located between the midbrain and the thalamus. It is crucial to various
pupillary reflexes.

Tegmentum
The tegmentum of the midbrain has these following important structures:

Oculomotor nucleus and trochlear nucleus;

Red nucleus has important interconnections to the cerebellum;

Substantia nigra; and

Superior cerebellar peduncle is composed of cerebellar axons passing to the thalamus.

The medial lemniscus passes laterally to merge with the spinothalamic fibers.

Base
The base of the midbrain (basis pedunculi or crus cerebri) is composed of descending axons that
divide into two functional groups.

-Pyramidal tract fibers (both corticospinal and corticobulbar fibers) are located in the middle 3/5
of the base.

-Corticopontine fibers occupy the medial and lateral 1/5 of the base of the midbrain.

Extending through the Whole Brain stem

The following structures are found throughout the brain stem:

-The reticular formation is a richly interconnected collection of nerve cells that perform a huge
number of homeostatic and control functions, such as:

-basic respiratory, cardiovascular and alimentary functions and rhythms;

- muscle tonus;
-consciousness and arousal; and
-reproductive behavior.

-The medial longitudinal fasciculus interconnects the nuclei of oculomotion (CN III, IV and VI)
and the vestibular nuclei.
 Central pathways for Cranial Nerve VII
Voluntary movements of the facial muscles are carried to the facial motor nucleus in the pons of
the brain stem via corticobulbar fibers that arise in the motor cortex. These axons travel via the
corticobulbar tract to the ipsilateral and contralateral motor nuclei of CN VIII in the pontine
tegmentum. Fibers that project to the part of the nucleus that innervates the forehead muscles
project bilaterally (dashed yellow and orange line below in Fig), but those that project to the part
of the nucleus that innervates the remaining facial muscles project only contralaterally.
After synapsing in the motor nucleus, the fibers course dorsally towards the floor of the 4th
ventricle and loop around the abducens nucleus to form a slight bulge in the floor of the 4th
ventricle, the facial colliculus (see Fig below). These fibers then turn ventrally to emerge on the
ventrolateral aspect of the brain stem at the caudal border of the pons, between CN VI and VIII.

Regarding the lesions – Stroke vs. Bell’s Palsy; this is UMN lesion vs LMN lesion:
UMN lesion results from damage to the UMN in the motor cortex or its axon that projects down
to the facial nerve nucleus. Voluntary control of ONLY the lower muscles of facial expression is
lost contralateral to the lesion (fig below on the left). UMN muscles of facial expression (above
the eyebrow) continue to function because the part of the nucleus that innervates them still
receives input from the ipsilateral hemisphere. The most common UMN lesion that involves CN
VII is stroke.
LMN lesion results from damage to the facial nucleus or its axons. ALL muscles supplied by the
nerve are paralyzed ipsilateral to the lesion. These lesions are commonly known as Bell’s
palsies. All actions of the facial muscles, whether voluntary, reflex or emotional are affected (fig
on the right).
Once you understand this, you might then be interested in this stroke case published in the New
England Journal of Medicine. A 72-year-old male presented with sudden onset of slurred
speech. He was unable to fully smile when asked to smiled on command (i.e. voluntary laugh),
due to facial paralysis on the left side. However, if he was made to laugh (i.e. emotional laugh),
he overcame his paralysis and exhibited a full smile! This is because there is preservation of
emotionally motivated facial movements, which means that emotionally motivated input to the
facial nucleus follows a different pathway than corticobulbar. Check it out at (it’s only 1 page):
http://www.nejm.org/doi/full/10.1056/NEJMicm0900573?query+TOC
 Sensory System Pathways
Visual Pathway

• Light passes through cornea (refraction)  aqueous humor & pupil (pupillary light
reflex)  lens (refraction & accommodation)  retina  photoreceptors are stimulated
(phototransduction, forming first image)  1. bipolar cell (second image)  2. ganglion
cell (third image) gives rise to the fibers in the:  3. optic nerve  optic chiasm  optic
tract  LGN of thalamus  4. optic radiation  visual cortex
Pupillary Light Reflex

• Input/afferent pathway: 1. Retina  Optic Nerve  Pretectal nuclei (bilateral in

midbrain)  2. Output/efferent pathway (parasympathetic): Bilateral Edinger-Westphal
nuclei  3. oculomotor nerves  ciliary ganglions  short ciliary nerves 
iris/pupillary sphincters (light in one eye makes both pupils constrict)
Pupillary Dilation

• 1st order neuron: hypothalamus to intermediolateral cells T1 cord  2nd order neuron
stellate ganglion  3rd order neuron along carotid artery to iris dilator (output is bilateral
so both eyes dilate simultaneously unless there is a Horner Syndrome)
Horizontal Gaze Pathway

• Right Gaze: System messages from left frontal eye field converge at right pontine
paramedian reticular formation (PPRF) or vestibular nuclei  CN right VI nucleus (in
pons)  motor innervation to right lateral rectus AND interneuron  travels through
left medial longitudinal fasciculus (MLF)  synapses at left medial rectus subnucleus in
CN III nucleus (in midbrain)  motor innervation to left medial rectus
Vertical Gaze Pathway Up

• Both frontal lobes  Superior colliculus (midbrain) and vestibular nuclei  System
messages converge at the midbrain in the rostral mesencephalic reticular formation (via
posterior commissure near aqueduct)  CN III nucleus  motor innervation inferior
oblique and superior rectus
Vertical Gaze Pathway Down

• Both Frontal or Occipital lobes  to III and IV nuclei  motor innervation to inferior
rectus and superior oblique
Auditory Pathway

• Hair cells of the organ of Corti transduce information to afferent cochlear nerves (CN
VIII, 1 neuron in spiral ganglion) dorsal and ventral cochlear nuclei of the medulla (2
neuron);  Inferior colliculus (3 neuron)
o Most axons cross to the contralateral side and ascend in the lateral lemniscus (the
primary auditory tract) to the inferior colliculus;
o Other axons remain ipsilateral (A small number of uncrossed fibers synapse in the
ipsilateral superior olivary nucleus from where they ascend in the ipsilateral
lateral lemniscus to the inferior colliculus)
• Inferior colliculus  medial geniculate nucleus of the thalamus (4 neuron)  auditory
cortex.
Olfactory Pathway

• Axons from olfactory receptor cells (1 neuron) leave the olfactory epithelium, pass
through the cribriform plate synapse on apical dendrites of mitral cells (2neurons) in
the olfactory bulb  the primary olfactory cortex, the piriform cortex in the temporal
lobe; Other projections of the olfactory bulb include: hippocampus, amygdala,
hypothalamus, reticular formation.
Taste Pathway

• Taste receptor cells (located in taste buds) transduce information to three cranial nerves
(CN VII, IX, and X; 1 neuron in Geniculate ganglion of VII, Inferior ganglion of CN IX,
Inferior ganglion of CN X)  brain stem, ascend in the solitary tract, and terminate on
2neurons in the solitary nucleus of the medulla project ipsilateral to the ventral
posteromedial nucleus of the thalamus (3neurons)  leave the thalamus and terminate
in the taste cortex in the insula.
Vestibular Pathway

• Hair cells of the semicircular canals, utricle and saccule transduce information to afferent
vestibular nerves (CN VIII, 1 neuron in vestibular ganglion) vestibular nuclear
complex of the medulla (2 neuron) the superior, medial, lateral (Deiters’ nucleus), and
inferior nuclei.;
o The secondary sensory neurons send their axons to the cerebellum and lower
motor neurons in the brain stem and spinal cord to help direct activity of the
muscles that maintain balance.
▪ All nuclei in the vestibular complex contribute fibers to the medial
longitudinal fasciculus (MLF). This pathway is primarily concerned with
maintaining orientation in space. The ascending MLF terminates
bilaterally within the nuclei of CN III, IV and VI, and by coordinating the
stimulation of extraocular muscles, allows the eyes to maintain fixation on
an object while the head is moving (the vestibuloocular reflex).
▪ The lateral vestibular nucleus (Deiter’s) sends a large group of axons
ipsilateral down the spinal cord to form the lateral vestibulospinal tract.
These axons facilitate the action of the lower motor neurons that innervate
the antigravity (extensor) muscles.
▪ The medial vestibular nucleus sends axons bilaterally to form the medial
vestibulospinal tract that is involved in relaxation of the muscles of the
neck and upper back.
▪ Secondary axons also make their way to the VPM of the thalamus (3
neuron) to the cerebral cortex for conscious perception of movement and
gravity.
 The Rules of 4 for Brain Stem Lesions
• 4 structures in the midline and begin with M:
1. Motor Pathway (corticospinal) – Lesion = contralateral weakness
2. Medial Lemniscus – Lesion = contralateral proprioception/vibration
loss
3. Medial Longitudinal Fasciculus – Lesion = ipsilateral internuclear
ophthalmoplegia
4. Motor Nucleus (of the Vagus) and nerve – Lesion = ipsilateral CN X
function loss
• 4 motor nuclei in midline and are those that are divisors of 12 (3, 4, 6, 12)
1. CN 3, 4, 6, 12 are midline
2. CN 5, 7, 9, 11 are lateral
• 4 structures to the ‘side’ (lateral) and begin with S:
1. Spinocerebellar pathway – Lesion = ipsilateral ataxia
2. Spinothalamic pathway – Lesion = contralateral pain and temp loss
3. Spinal nucleus of CN 5 – Lesion = ipsilateral pain and temp loss in the
face
4. Sympathetic pathway (autonomics) – Lesion = ipsilateral Horner’s
syndrome
• 4 CN in medulla, 4 in pons, and 4 above pons
1. 4 medulla cranial nerves
• Glossopharyngeal (CN 9) – Lesion = ipsilateral pharyngeal
sensory loss
• Vagus (CN 10) – Lesion = ipsilateral palatal weakness
• Spinal accessory (CN 11) – Lesion = ipsilateral shoulder
weakness
• Hypoglossal (CN 12) – Lesion = ipsilateral weakness of tongue
2. 4 pons cranial nerves
• Trigeminal (CN 5) – Lesion = ipsilateral facial sensory loss
• Abducens (CN 6) – Lesion = ipsilateral eye abduction weakness
• Facial (CN 7) – Lesion = contralateral lower facial weakness
• Auditory (CN 8) – Lesion = ipsilateral deafness
3. 4 cranial nerves above pons
• Olfactory (CN 1) – not in midbrain
• Optic (CN 2) – not in midbrain
• Oculomotor (CN 3) – Lesion = eye turned down and out
• Trochlear (CN 4) – Lesion = eye unable to look down when
looking towards nose
How to use these rules
Example lesion case:
A 60-year-old woman was referred to you because of recent onset of left
hemiparesis, left sided loss of proprioception and right-sided tongue deviation.
Where is the lesion?

How to approach this problem:

First, what are the signs and symptoms?

• left hemiparesis
• left sided loss of proprioception
• right-sided tongue deviation

Next, what are the structures that correlate with the symptoms?
• left hemiparesis Motor: corticospinal on right
• left sided loss of proprioception Medial lemniscus, right
• right-sided tongue deviation CN 12, right

Finally, where are these structures located in the brain stem?

• Motor: corticospinal on right Medial
• Medial lemniscus, right Medial
• CN 12, right Medulla

Where is the lesion?

Medial Medulla
 Brain Stem Lesion Syndromes
Lesion Diagram Structure Deficit
Posterior Superior colliculus Paralysis of upward
Midbrain and pretectal area (less frequently
(Parinaud) downward) gaze,
Syndrome pupillary
(lesion of the disturbances,
dorsal tectum, absence of
A in diagram) convergence
Cerebral aqueduct Obstruction leads to
noncommunicating
hydrocephalus
(bilateral
papilledema)
Pineal gland Inadequate
melatonin secretion
that may result in
insomnia
Paramedian CN III nucleus/root Ptosis, fixed and
Midbrain dilated ipsilateral
(Benedikt) pupil, complete
Syndrome ipsilateral
(lesion of the oculomotor paralysis
tegmentum, B (eye down and out)
in diagram) Dentatothalamic Contralateral
fibers cerebellar ataxia
with intention
tremor
Medial lemniscus Contralateral loss of
light touch and
position sensation
from the extremities
Medial CN III nucleus/root Ptosis, fixed and
Midbrain dilated ipsilateral
(Weber) pupil, complete
Syndrome ipsilateral
(lesion of the oculomotor paralysis
base of the (eye down and out)
midbrain, C in Corticospinal Contralateral spastic
diagram) tracts paralysis of
extremities
Corticobulbar Contralateral
tracts weakness of lower
face (CN VII), tongue
(CN XIII), and palate
(CN X), uvula points
 away from the
lesion, protruded
tongue points
toward lesion
Medial Corticospinal Contralateral
Medullary tracts hemiparesis of the
Syndrome (A trunk and
in diagram) extremities
Medial Lemniscus Contralateral loss of
proprioception,
discriminative tactile
sensation, and
vibratory sensation
from the trunk and
extremities
CN XII Ipsilateral flaccid
paralysis of the
tongue (tongue
points to side of
lesion)
Lateral Vestibular Nuclei Nystagmus, nausea,
Medullary (medial and vomiting, and vertigo
(Wallenberg) lateral)
Syndrome (B Inferior cerebellar Ipsilateral cerebellar
in diagram) peduncle signs (dystaxia,
dysmetria, and
dysdiadochokinesia)
Nucleus Ipsilateral laryngeal,
ambiguous pharyngeal, and
palatal paralysis (loss
of the gag reflex
[efferent limb],
dysarthria,
dysphagia, and
dysphonia
[hoarseness])
Spinothalamic Contralateral loss of
tracts pain and
temperature
sensation from the
trunk and
extremities
Spinal trigeminal Ipsilateral loss of
nucleus pain and
temperature
sensation from the
face
 Descending Ipsilateral Horner
sympathetic tract syndrome (ptosis,
miosis,
hemianhidrosis,
vasodilation, and
apparent
enophthalmos)
Medial CN VI nucleus Lateral gaze palsy
Inferior Corticospinal tract contralateral
Pontine hemiparesis of the
Syndrome (A trunk and
in diagram) extremities
Medial lemniscus Contralateral loss of
proprioception,
discriminative tactile
sensation, and
vibration sensation
from the trunk and
extremities
Medial Internuclear
longitudinal ophthalmoplegia
fasciculus (MLF)
CN VII lower Ipsilateral Bell palsy
motor neuron without forehead
sparing
Lateral Lateral Contralateral loss of
Inferior spinothalamic pain and
Pontine tract temperature
Syndrome (B sensation from the
in diagram) trunk and
extremities
CN VIII Vertigo, hearing loss,
tinnitus, nystagmus
CN VII Bell palsy without
forehead sparing
Middle cerebellar Ipsilateral ataxia
peduncle
Spinal trigeminal Ipsilateral
nucleus/tract pain/temperature
loss (face)
Descending Ipsilateral Horner
sympathetics syndrome
Lateral CN V complete ipsilateral
Midpontine trigeminal paralysis
Syndrome (paralysis of muscles
(purple of mastication, jaw
deviation to paretic
shaded area side, facial
in diagram) hemianesthesia, loss
of corneal reflex)
Middle cerebellar Ipsilateral limb and
peduncle gait dystaxia

Lateral Superior and Ipsilateral limb and

Superior middle cerebellar trunk dystaxia
Pontine peduncles
Syndrome Dentate nucleus Signs similar to those
(turquois seen with damage to
shaded area the superior
in diagram) cerebellar peduncle
(dystaxia, dysmetria,
and intention
tremor)
Spinothalamic and contralateral loss of
trigeminothalamic pain and
tracts temperature
sensation from the
trunk, extremities,
and face
Descending Ipsilateral Horner
sympathetic tract syndrome
Medial lemniscus Contralateral loss of
proprioception,
discriminative tactile
sensation, and
vibration sensation
from the trunk and
lower extremity
 Pharmacology of the Eye
Drug Delivery
1. Topical: Topically applied drugs can be absorbed across the cornea and conjunctiva and into
the aqueous humor. The drug can gain access to the system circulation via the aqueous humor
and by nasolacrimal drainage.
• Drops
o Simplest and most convenient
• Ointment
o Increases the contact time of ocular medication to ocular surface for a better
effect; disadvantage is temporary blurred vision
• Gel
• Via soft contact lens
o Used to deliver an adequate supply of medication at a steady-state level

2. Periocular injections: Reach behind iris-lens diaphragm better than topical application. This
route bypasses the conjunctival and corneal epithelium, which is good for drugs with low lipid
solubility; Anesthetics and steroids are applied this way.
• Sub-conjunctival
o Used to achieve a higher concentration and when drugs can’t penetrate cornea due
to large size
• Subtenon
o Anterior subtenon used for disease anterior to the lens
o Posterior subtenon used for disease posterior to the lens
• Peribulbar
o Used for anesthesia, optic neuritis
• Retrobulbar
o Used for anesthesia

3. Intraocular
• Intracameral
o Administration route for drugs during cataract surgery
• Intravitreal
o Used for administration of antibiotics in cases of endophthalmitis, steroid
administration in macular edema
4. Systemic
• Oral
• Intravenous
• Intramuscular
Common ocular drugs
1. Antibacterial drugs
• Ciprofloxacin
• Erythromycin
• Gentamicin
Used topically, orally, intravenously and intravitreally
Indications: ocular bacterial infections, preseptal cellulitis, orbital cellulitis, endophthalmitis
2. Antiviral drugs
• Acyclovir
• Trifluridine
Used as ointment, oral and intravenously
Indications: HZ keratitis, viral uveitis
3. Antifungals
• Amphotericin B
• Ketoconazole
• Flucytocine
Indications: Fungal corneal ulcer, fungal retinitis/endophthalmitis
4. Mydriatics and cycloplegics (Agents used for eye examination)
• Tropicamide (short acting (4-6 hours))
• Homatropine (intermediate acting (24 hours))
• Atropine (long acting (2 weeks))
These agents dilate the pupil, are all muscarinic antagonists
Indications: Normal ophthalmologic exam, corneal ulcer, uveitis, cycloplegic refraction
• Phenylephrine
Alpha-1 receptor agonist; causes mydriasis without cycloplegia
Indications: Facilitates examination of the eye
5. Antiglaucoma
• Cholinomimetics:
o Pilocarpine (direct muscarinic agonist); stimulates muscarinic receptors on ciliary
muscle causing contraction and helping to open the angle to the canal of Schlemm
o Physostigmine (cholinesterase inhibitor); increases local Ach causing increasing
ciliary and sphincter muscle contraction
• Beta blockers (MOST COMMON for treatment of glaucoma): Timolol, betaxolol
Mechanism: Reduces intraocular pressure
• Carbonic anhydrase inhibitors: Acetazolamide, dorzolamide
 Mechanism: Reduces aqueous humor formation
• Hyperosmotic agent: mannitol
Mechanism: Reduces intraocular pressure
Indications: Used when IOP is very high
6. Immunomodulatory agents
• NSAIDS: Ketorolac, indomethacin
Indications: Scleritis, uveitis, also used preoperatively to maintain dilation of pupil
• Corticorticoids: Hydrocortisone, dexamethasone
Indications: Allergic conjunctivitis, scleritis, uveitis, allergic keratitis, after ocular
surgeries
• Antihistamines: Olopatadine
Indications: Block histamine release from mast cells in response to allergic conjunctivitis
7. Ocular lubricants
• Restasis
• Refresh tears; various commercial brands available
Indications: ocular irritations in various diseases, dry eyes
8. Eye anesthetics
• Propacaine, tetracaine
Indications: tonometry, removal of corneal foreign bodies, removal of sutures, examination
of patients who cannot open eyes because of pain
• Lidocaine, bupivacaine
Indications: anesthesia and akinesia for intraocular surgery
 Nystagmus
Nystagmus is defined by the direction of the fast component
 It is in the direction of the head’s rotation

 In the example below: rotate head left, slow component is to the right, fast
component is to the left: this is a left nystagmus

When the head is rotated left, initially, the endolymph will "lag" to the right creating increased
firing of the receptors in the ampulla of the left horizontal canal and decreased firing of the
receptors in the ampulla of the right horizontal canal. This gives us the "normal" sensation of
rotating to the left and the vestibulo-ocular reflex will assist the eyes in also moving to the left.
Post-rotational Nystagmus (i.e. what happens after you get off the Tea Cups ride at Disney
Land)
Now, rotate for a total of ten revolutions. By the tenth revolution, the endolymph has also started
moving to the left and has "caught up" with the movement of the canal so there is relatively no
movement of fluid in relationship to the canal and the receptors in both ampulla are "silent"! The
hair cells would be standing straight up.

Next, stop suddenly. Now, the fluid continues to move to the left though the subject is still. This
causes increased response from the receptors in the ampulla of the right horizontal canal and
decreased response from the receptors in the ampulla of the left horizontal canal. This is
interpreted as meaning the head is rotating to the right even though it is still! Therefore, the eyes
will reflexively turn to the right due to the vestibulo-ocular reflex. This reflexive movement of the
eyes to the right is referred to as post-rotary nystagmus. The subject realizes his head is not
rotating and therefore brings his eyes back to midline. The reflex continues to move the eyes to
the right, however, and you will see a back and forth movement of the eyes for up to
approximately 20-30 seconds until the endolymph stops moving.
 If the rotation is stopped abruptly, the eyes move in the direction opposite the original
rotation.

 The person tends to fall in the direction of the original rotation

 Due to stimulation of contralateral extensor muscles

 The person thinks he/she is spinning in the opposite direction

 Summary:

 A left rotational nystagmus

 A right post-rotational nystagmus

 And the person falls to the left

 Direction of Movement in Types of Nystagmus
Form of Nystagmus
Rotary nystagmus (i.e. while
spinning in a circle)
Postrotary nystagmus (i.e.
stopping after spinning in a
circle)
Caloric nystagmus
Warm water placed in one
ear
Cold water placed in one ear
Direction of Fast Phase
Same as direction of rotation
Opposite direction of
rotation
Toward the ear with warm
water
Away from the ear with cold
water
Direction of Slow Phase
Opposite direction of
rotation
Same as direction of rotation
Away from the ear with
warm water
Toward the ear with cold
water

Mnemonic: COWS; cold opposite, warm same for the direction of movement of the fast phase