The neurological brainstem: locked-in a small space

Introduction
The brainstem is very small structure packed in the posterior cranial fossa, which has a length of
10-12 cm and a diameter which depending on the region range from 2 to 5-6 cm. 

Being all packed together even a small lesion of a specific part will cause major symptoms,
substantial deficit: multiple sensory, motor and neuro-regulatory problems; when this occur we talk
about brainstem syndrome.

Definition
Brainstem stroke syndromes, also known as crossed brainstem syndromes, refer to a group of
syndromes that occur secondary to lesions, most commonly infarcts, of the brainstem so vascular
problems which in most of the case are due to posterior circulation involvement so mainly
vertebral arteries and basilar artery. (even if of course there are other possible pathologies which can
result in the same subset of symptoms).

RM: Whenever there is vertigo and nausea it’s of

mainstay importance to distinguish in between
peripheral problems of inner ear and a central
problem of the vestibular nuclei, brainstem or
cerebellum.
Moreover it’s also crucial to distinguish in
between problems coming from brainstem strokes
and damages and problems due to higher cortical
infarcts or damage. Usually, hoverer, there are
suggestive features which point towards cortical
involvement which are higher functions problems
such as aphasia, hemineglect, heminanopia,
seizures.

Why crossed signs ?

Each brainstem stroke syndrome has a
characteristic clinical picture according to the involved area, however, generally, there is:
• Ipsilateral cranial nerve palsy or sensation loss: so depending of the cranial nerve affected we
can have motor or sensory problems or both.
• Contralateral hemiplegia/hemiparesis and/or hemisensory loss.
This can be explained by the fact that most tract traversing the brainstem carry signal from the
contralateral body and instead all nuclei of the cranial nerves (except 4th) supply ipsilateral
structures.

Ocular abnormalities: this are major signs of possible brainstem syndrome due to the fact that CN
3rd, 4th and 6th are all three involved in control of eye movements and also regulation of pupillary
size (2nd and 3rd CN). Moreover in the brainstem we also find gaze centers which control scanning
movement of the eye, lateral gaze is controlled by the para-median pontine reticular formation
(PPRF) while the vertical gaze is controlled by the rostral interstitial nucleus of medial longitudinal
fasciculus and others (interstitial nucleus of Cajal, nucleus of Darkschewitsch… all located in the
rostral midbrain while lateral gaze centers as we said are in the pons).
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Most common brainstem syndromes: not all to be known see lect- 2 of Barajon for further details

Outer brainstem anatomy review

Grossly speaking the brainstem is made up by three portions: the midbrain, in continuity with the
diencephalon, the pons of Varolio and the medulla oblongata which is in continuity with the spinal
cord; dorsally to these structures we find the cerebellum which is connected with the brainstem by
six bundles (3 pairs) of white matter called cerebellar
peduncles.
RM: this is why if a patient has a lesion in the brainstem
involving one or more of these peduncles the signs and
symptoms associated will be the same as the ones of a
cerebellar lesion proper.

As said before, the brainstem lies in the posterior cranial

fossa enclosed by the occipital bone, the clivus of the
basilar process of the occipital bone; also the cerebellum
lies in the same fossa and both these structures are
enclosed in a tight compartment which lies underneath the
tentorium cerebelli (infra-tentorial compartment).
RM: within the cranial cavity, the meningeal layer of dura mater (2nd layer, innermost, the other is
the outer periosteal layer of dura mater) folds in on itself in several areas to form dural reflections,
or septa known as:
•falx cerebri between the cerebral hemispheres,
•tentorium cerebelli between the cerebral hemispheres and
cerebellum/ brainstem; attaches anteriorly on the petrous
portion of the temporal bone and on the clinoid processes of
the sphenoid bone.
•falx cerebelli between the cerebellar hemispheres,
•Diaphragm sellae, a smaller reflection, covers the pituitary
fossa and underlying pituitary gland.

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Due to the fact that these structures are so packed, if there is
something which increase the pressure in the infra-
tentorial compartment as a tumor of the cerebellum or an
hemorrhage, the cerebellum will start to expand and can
compress the brainstem or we can also have an herniation of
the cerebellum thought the foramen magnum. These are life-
risk situation requiring emergency intervention due to the
fact that in the brainstem we find vital centers as part of the
ARAS (ascending reticular activating system).

Macroscopic aspects: ventral aspect of the brainstem (this

surface lies on the occipital bone clivus)
Starting from down going upward we find the medullary
pyramids which are separated from the pons by the bulbo-pontine groove, the pyramids are
important cause they contain the most important voluntary motor pathway which is the portico-
spinal tract or pyramidal tract.
Caudally we can see a transverse bundle of
white matter which is referred to as the
decussation of the pyramids which is
where most of the fibers of the cortico-
spinal tract cross contra-laterally: RM: any
lesion which is above this point will cause
contralateral damages and signs and
symptoms while if the damage is below
then they will be ipsilateral.

Moving laterally from the pyramids there

are two protrusions which are the olives,
and they correspond on the inside to the
inferior olivary complex or nucleus which
are important for projection to the cerebellar cortex (climbing fibers).

Medulla
Both in the bulbo-pontine groove and in the small groove which separate the pyramids from the
olive there are the origin of some CN, again starting from down and going upward we find the
origin of the 12th CN hypoglossal nerve, in the groove between the olive and the pyramid; slightly
behind the olive instead, we find the exit of the CN 9th glossopharyngeal (slightly superiorly) and
CN 10th vagus.

Even behind them there is the exit of the CN 11th accessory, which however originate mostly from
fibers of the cervical segments of the spinal cord and in fact there are multiple fibers continuously
exiting from the medulla oblongata and downwards from the spinal cord (these will enter the skull
throughout the foramen magnum and join the fibers from the medulla to give rise finally to the
accessory nerve, which then comes out from the skull through the jugular foramen).
In the bulbo-pontine groove instead from medial to lateral there are the origin of the 6th CN
abducens, the 7th CN facial and intermedius and then the 8th CN vestibulocochlear.
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Pons
The pons, has a smoother surface which respect to the medulla, there is a shallow groove on the
midline (for the basilar artery), laterally to which there is the exit of the 5th CN trigeminus, motor
and sensory roots.

Midbrain
Going rostrally, into the midbrain ventral surface which is referred to as the ventral crux or brain
peduncle (white matter extensive bundles) in between of which there is the inter-peduncular fossa,
with the exit of the 3rd CN oculomotor.
Moving laterally from the peduncles there are two nerves embracing on the side the peduncles
which correspond to the right and left 4th CN trochlear, which is the only nerve which emerge
from the brainstem posteriorly and not anteriorly or antero-laterally.

Macroscopic aspects: dorsal surface

The cerebellum has been
removed to show us a fossa
underneath which correspond to
the rhomboidal fossa (floor of
the 4th ventricle), there are two
triangles, the inferior one
correspond to the open portion
of the medulla oblongata (BB
review: the vesicle which give
rise to this part, the rhombo-
encephalic vesicle undergoes to
a book like opening in the
region where it forms the pons
and the rostral portion of the
medulla, while the lower part
it’s called the closed portion).

Grossly we can see that this dorsal aspect is not smooth, there are bulging, striae:
• The vagal trigone, which correspond to the inside to the dorsal motor nucleus of the vagus nerve.
• The hypoglossal trigone, where we find the motor nucleus of the hypoglossus.
• The facial colliculus, where the fibers of the 6th CN abducens cross above the motor nucleus of
the facial nerve giving rise to this protrusion.
• The striae, where the acoustic fibers cross from one side to the other
• The obex, which can be used as a reference point because is at the level at which the 4th ventricle
communicates with the spinal canal (upwards instead it communicates with the 3rd ventricles
which is in the diencephalon through the Silvian aqueduct, located in the tegmentum of the
midbrain).
• The gracile (medial) and cuneate (lateral) tubercle, at the side oof the obex, still in the closed
portion of the medulla, which are where the dorsal columns of the spinal cord end up, these nuclei
are the first relay station of the dorsal columns medial lemniscus pathway which bring
information of proprioception, vibration and fine touch.
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 •The lamina quadrigemina, at
the level of the midbrain (part of
the tectum), which is made by
two superior colliculi (in
between of them we find the
pineal gland which however
belongs too the epithalamus)
which are connected to the
lateral geniculate bodies
(diencephalon, visual pathway)
by means of tiny bundles of white
matter called brachia conjunctiva.

Two inferior colliculi (caudal to
which we find the exit of the 4th
CN throclear upon the roof the
4th ventricles which is the
medullary velum), which are
connected to the medial
geniculate bodies (diencephalon, auditory pathway) again by the inferior brachia conjunctiva.

4th ventricle overview

Dorsally to the pons and medulla, we find as we
said above the 4th ventricles, which has a typical
elongated shape; if there is an hemorrhage or a
tumor of the cerebellum, it can compress the 4th
ventricles and its communications with the spinal
canal or the Silvian aqueduct and 3rd ventricle.

Moreover caudally to the 4th ventricle we find

the cisterna magna, the Ponto-cerebellar cistern,
which is in communication with the 4th
ventricles by means of three foramina which are
the foramina of Magendi and the foramen of
Luschka; if we have a compression in this point
CSF which is produced in the ventricles can’t enter the subarachnoid space (as this is the only point
in which the ventricular system communicate with the sub-arachnoid space) leading to an increase
of CSF inside the ventricular cavity (hydrocephalus) and in increase of intracranial pressure with
compression of the cerebral cortex from the inside to the outside.
RM: CSF is then reabsorbed at the level of the Venus sinuses, as in the granulation of the superior
sagittal sinus etc…

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Cranial Nerves functions and signs and symptoms
As we said before ten out of twelve of the
cranial nerves originates from the brainstem
(the olfactory nerve CN 1st instead originates
from the telencephalon while the optic nerve
CN 2nd originates from the diencephalon).

Functions review
CN 12 hypoglossus: intrinsic muscles of the
tongue, so lesions here will give problem in
moving the tongue.
Lesions of this nerve will cause hemiparalysis
of the tongue which will point toward the
affected side

CN 11 Accessory: it innervates muscles of

branchial origin as the sternocleidomastoideus
and part of the trapezius.
Lesions to this nerve will result in weakness
in ipsilateral shoulder and difficulty in turning
the head to the opposite side with respect to
the lesion.

CN 10 Vagus: it has several components:

• Visceral sensory: special for taste, especially posterior 1/3 of the tongue, epiglottis and pharynx
and general visceral sensory: chemo- and baroreceptors of the aortic arch but also a lot of viscera
in neck, thorax and abdominal cavity are innervated by the vagus.
• General somatic sensory: from a small territory in the ear and the external auditory meatus
• Para-sympathetic component: viscero-motor parasympathetic of stomach duodenum, kidneys and
large intestine up to the right 2/3 oof the transverse colon while the rest come from the sacral
segments of the spinal cord; but also some striated muscles of branchial origin as pharyngeal and
laryngeal muscles.
Lesions to this nerve will result in ipsilateral paralysis of the soft palate, problem in controlling the
pharynx and larynx (dysphonia, hoarseness, with a sort of deep voice) dyspnea, dysarthria (problem
in articulation), dysphagia (swallowing).
Loss of gag reflex (in this case due to loss of motor component of the reflex arch), unilateral loss of
cough reflex (sensation or irritation of the mucosa of larynx and pharynx should be sensed by the
vagus).

CN 9 glossopharyngeus: several components

• Special sensory, taste as the vagus
• General visceral sensation: chemical and baroreceptors of carotid bodies but also visceral
sensation of larynx and pharynx
• Parasympathetic to the parotid gland
• Branchial motor too stylopharyngess muscle
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 Lesions of this nerve will result in loss of taste (not complete) and visceral
sensory from the pharynx, loss of gag reflex (due to loss of the sensory part of
the reflex arch, instead the motor part is innervated by the vagus so intact) and
loss of carotid sinus reflex (giving rise to orthostatic hypotension, due to
defects on the normal stimulus which in the passage from lying to standing
position should cause an increase in hearth rate and vasomotor control in order
to keep an adequate BP).

CN 8 vestibulocochlear: carries only special somatic cause it has to do with

vestibular and auditory sensations
Lesions to this nerve will cause ipsilateral hearing loss (even if acoustic
pathways are highly bilateral so you don’t really became deaf, tinnitus
(ringing sensation), disequilibrium associated with vertigo and nystagmus
(which is made by two phases, a slow movement followed by a rapid saccadic
movement).

CN 7 facial: several components:

• General somatic sensory from a small territory in the ear near to the external acoustic meatus
• Visceral special sensory, taste of anterior 2/3 of the tongue (in fact is the facial nerve which is
mostly responsible for taste sensation+ vagus and glossopharyngeus contribution)
• Parasympathetic pre-ganglionic, to lacrimal glands, glands of the nasal mucosa and to salivary
sublingual and submandibular glands
• Striated muscle of branchial origin, mimic muscle of facial expression, the stapedius (in the
middle ear, responsible for protection and regulation of sound intensity, controls how sound
transduction take place together with the tensor tympani muscle, innervated by the trigeminus)
and part of the digastric muscle.

RM whenever there are earring acoustic problems, these can also be related to facial nerve
damage
Lesions to this nerve will cause loss of mimic muscle so ipsilateral flaccid paralysis, loss of taste
(ageusia, anterior 2/3 of the tongue), reduced salivation, hyperacusis (stapedius), loss of corneal
reflex (in this case due to motor component loss, orbicularis muscle).

CN 6 abducens: somatic motor innervation of lateral rectus muscle of the eye

Lesions of this nerve will cause ipsilateral paralysis or weakness of lateral rectus, which result in
horizontal diplopia, so double vision, which manifest ocularly in the patient into convergent
strabismus (esotropia when the patient look straight the affected eye is turned inward).
Strabismus by definition is a deviation of the eye that the patient cannot overcome; the visual axes
assume a position relative to each other different from that required by the physiological conditions.
This can be a sign of a peripheral lesion of a cranial nerve but can also be present in case of lesion
inside the brainstem (usually associated to other signs).

CN 5 trigeminus:
• General somatosensory, touch, pain, temperature, joint position and vibration of the territory of
the face, mouth, nasal sinuses and meninges
• Motor, mandibular branch to masticatory muscles and also tensor tympani
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Lesions to this nerve will cause sensory loss from the face, mucosa of oral and nasal cavity; loss
oof corneal reflex (sensory component oof the reflex), flaccid paralysis of masticatory muscles,
deviation of the jaw toward the weak side, and hypoacusis (tensor tympani loss).

CN 4 throclear nerve, somatic motor to superior oblique muscle

Lesions to this nerve will cause extortion of the eye and weakness in downward gaze, vertical
diplopia with head tilting trying too compensate the extortion of the eye

CN 3 oculomotor:
• Somatomotor to all other extrinsic muscle of the eye not innervated by abducens or throclear
• Parasympathetic too pupillary muscle, sphincter muscle oof the pupil and ciliary muscle for
accommodation

RM normally one or more cranial nerve get involved if we have a problem at the level of the
brainstem either directly or in the circuitry of the RF which controlled them (reflexes), so being able
to identify immediately which one is involved can give information about the level at which the
lesion has occurred.
Ex: if there is a lesion of the hypoglossus (problems in moving the tongue) the lesion can’t be at the
level of the midbrain, but probably it’s ipsilateral at the level oof the medulla.
Lesions of this nerve will result not only in somatomotor loss (as lesions of the 6th and 4th CN),
but also due to the fact that this nerve contain pre-ganglionic parasympathetic fibers for the ciliary
muscles and the intrinsic muscles of the pupils the patient will present with diplopia, ptosis (loss of
control of levator palpable superior) and the affected eye will look outward and down (loss of
medial superior and inferior rectus and also of inferior oblique muscle) and the eye will show
mydriasis (dilation, loss of constrictor pupils so the sympathetic tone prevails, dilator pupils) and
loss of accommodation.

Internal anatomy of the brainstem

Internally the brainstem can be divided into three strips, a base, most ventral portion, present in all
the three parts of the brainstem, a tegmentum, also in all the three and then the tectum, which
instead represent the lamina quadrigemina and so it’s only at the
level of the midbrain.
Inside the brainstem and particularly in the tegmentum
(exception pontine nuclei, newest phylogenetically) we find
nuclei of the cranial nerves, specific nuclei of the brainstem
(relay nuclei, interposed in ascending, descending pathways or
correlative circuitry as the inferior olivary nuclei containing fibers
going to the cerebellar cortex, cuneate and gracile nuclei…), the
reticular formation (vital centers) but also pathways running there (ascending and older
descending pathways and laterally cerebellar peduncles). Newest descending pathways instead run
in the base, which contains mostly white matter so axons of newest pathway as cortico-spinal tract.
Nuclei of cranial nerves
In the brainstem we don’t find the same organization of motor and sensory territory as in the spinal
cord, in most of the brainstem due to the book-like opening embryologically; what was anterior in
the spinal cord became medial in the brainstem and what was posterior in the spinal cord became
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 lateral in the brainstem (this is valid for most portions cause we also
have the closed portion of the medulla).
So in most portion of the brainstem, the position of cranial nerve nuclei
goes from medial to lateral and instead of four main territories as in the
spinal cord (somatomotor, anteriorly medially visceromotor, anteriorly
laterally, somatosensory, most posterior laterally and viscerosensory
posteriorly medially), there are seven territories concerning the nuclei
of the cranial nerves, we have:
•Somatomotor: striated muscle of somitic origin
•Somatomotor’: striated muscle oof branchial origin
•Visceromotor
•Viscerosensory
•Special viscerosensory:
tiny part reserved to taste
•General somatic afferent
•Special somatic afferent:
for hearing and vestibular
organ

Rm: this nuclei form discontinuous columns inside

the brainstem (differently from spinal cord), and this
is why if we have a lesion in the brainstem, not
always we will have problems which should be
associated to that region, because maybe at that
specific point there are no nuclei present so it depends
on the level of the lesion.
Focus on nuclei in medulla, pons and midbrain

Open
portion, from medial to lateral dorsally we can see:
•The nucleus of the hypoglossus
•The dorsal motor nucleus of the vagus
•The nucleus of the solitary tract: viscerosensory
and visceromotor
•Outermost vestibular nuclei
•The spinal trigeminal nucleus: also called nucleus
of the descending route of the trigeminus (called so
because it continues in the tegmentum of the
brainstem up to the higher cervical centers of the
spinal cord), it’s caudal most of the three sensory nuclei of the trigeminous in the brainstem; the
other two are one in the pons (main sensory nucleus) and one in the midbrain.
• The nucleus ambiguus, it’s a motor nucleus which contains mostly fibers which innervate
striated muscle of branchial origin as pharynx and larynx but together with the dorsal motor
nucleus of the vagus also contains pre-ganglionic parasympathetic neurons

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 PONS: we can see medially the abducens nucleus,
laterally the vestibular nuclei (partially in the medulla as
seen before and partially in the pons), and in green the
continuation of the spinal nucleus of the trigeminous that
as we said it’s gonna end up in the main or chief nucleus of
the trigeminous.

MIDBRAIN:
•Lower caudal part left: close to the midline we find the
motor nucleus of the 4th CN trochlear
•Upper rostral part right: close to the
midline the motor nucleus of the 3rd
CN oculomotor associated to the
nucleus which contain pre-ganglionic
parasympathetic neurons which is the
Edinger-Westphal nucleus

RM As we said if we have a lesion in

the brainstem, there can be or not signs
and symptoms related to involvement of nuclei of CN but signs and symptoms related to
pathways running there as for examples fibers of dorsal column medial lemniscus pathway
will always be present because the pathway runs medially all throughout the brainstem (presenting
as contralateral loss of sensation of fine touch, vibration and proprioception). However according to
associated CN signs presenting we can have a hint on where the lesion is in the brainstem.

Specific nuclei or relay nuclei

From rostral to caudal, in the midbrain
tegmentum we find the red nucleus (which
contains magno- and parvicellular portions
involved in connection of the cerebellar
cortex with the cerebral cortex, not so
important in humans as part of the cerebello-
dento-rubro-thalamo-cortical tract), the
substantia nigra (dopaminergic system, basal
ganglia circuitry), the peri-acqueductcal
gray matter, which is important for pain
control, visceral functions and locomotion.
Then in the pons there is the nucleus of the lateral lemniscus, which carries auditory information,
and this is one of the many nuclei involved in processing of acoustic informations.
We also find the superior olivary nucleus and the trapezoid body nucleus, which are important
for sound localization, this nucleus receive information from ipsi- and contralateral ear.
The inferior olivary nucleus, as said before projection to cerebellum, climbing fibers and cuneate
and gracile nuclei, first relay station of dorsal columns medial lemniscus pathway.

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 In the base of midbrain and pons there is a big amount oof white matter
which is no longer present in the medulla, this contains together with cortico-
spinal tract fibers also lot’s of fibers of the cerebral peduncle (cortico-
pontine tract) which contain fibers from the cortex to the basilar pontine
nuclei (which being newest phylogenetically are in the base) and they then
project to the Neo-cerebellum by means of the middle cerebellar peduncle.

The reticular formation

Its a very big amount of neurons organized as a network in the tegmentum of
the brainstem, and extending up to the cervical segments of the spinal cord; it contains severals
centers, among which (listed below and explained after):
• Pain modulatory centers
• Vital centers
• Autonomic centers
• Reflex centers
• Muscle tone/movement control
• Temperature control
• Consciousness
• Eye movements

Morphologically speaking these neurons can be divided according to their size into:
• Parvo-cellular neurons, small, involved in local circuitry as rhythmic generators, laterally, these
are usually responsible for:

-reflexes

-stereotype behaviors mediated by CN as breathing and swallowing
• Magnoocellular neurons, closed to the midline raphe, these have
long ascending and descending axons and usually are involved in:

-arousal (ARAS)

-movement control

-pain

-posture control 

-autonomic functions
• Intermediate region

Functionally (neurochemical) speaking instead the RF can be divided based
on the major type of neurotransmitter released in that region: dopamine,
serotonin, acetylcholine, epinephrine, norepinephrine, histamine:

• Raphe nuclei on midline, mostly serotoninergic projections

• Laterally in the pons and medulla there are noradrenergic and adrenergic
centers, as the locus ceruleus in the pons and brachium pontis.
• The substantia nigra (not properly part of RF) and the midbrain contain
most dopaminergic centers together with medially the ventral segmental
area. These are involved in the meso- limbic, striatal and cortical circuitry.
• Cholinergic projections are more spars, in continuity with the basal
forebrain nuclei.
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 Detailed explanation of RF functions
• Pain modulatory centers: mostly decrease (some rare increase) transduction of pain sensation
in the dorsal horn of the spinal cord by means of descending pathways (noradrenergic locus
ceruleus in pons, serotoninergic rostral ventro medial medulla RVM) and moreover the peri-
acqueductal gray is involved in modulation of the two stated above.
• Vital centers: 

-Cardiovascular, cardiac accelerator and slowing centers, mostly in the medulla, they control the
hearth rate and the state of contraction of blood vessels via the autonomic nervous system (they
project to the motor nucleus of vagus which contain pre-ganglionic parasympathetic fibers to
hearth or RF from which they reach the spinal cord). They do this through information coming
from the nucleus of the solitary (baro- and chemo-receptors, and state of stretch of hearth
chambers) 

-Multiple respiratory centers (several region in the
brainstem are necessary for generating the rhythm of
breathing, detecting info from periphery about CO2/O2
conc. in blood, ph; also the nucleus of the solitary tract in
involved in respiratory control, it receive visceral sensory
information from CN 7th-9th-10th which are related then
to centers of reticular formation for different reflexes).

•Reflexes: vital as reflexes to protect the upper respiratory airways

Abnormal breathing patterns
(cough), it helps dislodging mucus from the airways, or get trigged
when irritants enter the airways. This is under control of center in the
medulla RF which work as a central pattern generator + again the
nucleus oof the solitary tract, which sense the stimuli and activate the
deputed centers. Impaired cough reflex, can be caused either by lesions
in the brainstem involving the nTS (input sensory loss), either because
the CPG so RF is involved but also if there is a lesion impairing the
motor nucleus of the vagus
nerve.

VRG: ventral respiratory group

CPG: central pattern generator 


nTS: nucleus tractus solitarius

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Another important reflex is swallowing, it requires:
• The nTS (sensory part of the reflex when the bolus
touches the roof of the soft palate and oropharynx),
• RF (swallowing centers in lateral medulla, dorsal
and ventral group),
• Association with respiratory centers (to interrupt
breathing act while swallowing occurs),
• The effector component, nucleus ambiguus,
which control the brachial muscle.
Rm: in the babies swallowing can occur also during
breathing thanks to a higher position of the larynx. Control of reflex swallowing, solid line=facilitative pathways,
broken line=inhibitory pathways.

Vomiting: this is again a protective reflex, it requires

more than one region:
•RF of medulla oblongata called vomit center,
•Area postrema, associated to floor oof 4th ventricles, it’s
a chemo-receptors trigger zone
•nTS functioning as a afferent component from viscera

Several things can trigger vomit reflex, some can come

from blood, blood born emetics, as drugs, acting on vomit
center either reaching the area postrema, where the BBB is
reduced or because are absorbed by the small intestine and
then they trigger the activity of the nTS.
Local irritants as radiation, bacterias or viruses can trigger
vomiting by causing inflammation of intestinal mucosa,
again sensed by the nTS. Also higher centers can trigger vomiting, such as in case of a violent
emotional reaction (memory, fear, dread, pain and
anticipation).

GAG reflex: requires

• Lateral tegmentum of medulla RF
• Afferent component by nTS or glossopharyngeal
• Efferent component by nucleus
ambiguus, which activate muscle of
the posterior pharynx and soft palate.

HICCUPS: peritoneal, upper airways

and diaphragm irritation can generate this fastidious sensation. This is controlled
by a brainstem center (in the zone where also the nucleus ambiguus is localized)
and a center inside the motor segments of the spinal cord. Hiccups in most cases
can be easily resolved, still if it’s continuous and persistent it need to be
investigated as it can be due to a problem in the medulla of the brainstem.

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Pupillary reflex
It’s a consensual reflex, in normal conditions testing the reflex on one side,
should elicit a response also on the other side; it requires:
•The retina
•The visual pathway
•The Edinger-Westfal nucleus (midbrain)
•The parasympathetic NS

Afferent branch of reflex: light is shined on the retina and get captured by
photoreceptor there, this information about light is carried in the visual
pathway by the 1st CN, optic nerve.

Then information pass thought the optic chiasm (where nasal fibers of each
retina, responsible for peripheral vision cross contra-laterally) to generate the
optic tract which has a lateral division, going to the lateral geniculate bodies
and then to the cortex, and a medial division, the one responsible for the
reflex, which brings light information to the superior colliculi/ pre tectal area. From the pre tectal
area through the posterior commissure informations also reach the other side

Efferent branch of the reflex: is carried on by parasympathetic fibers innervating smooth muscle
(constrictor/sphincter pupils) of the Edinger-Westfal nucleus, which exit the brainstem with the
oculomotor nerve in the inter-peduncolar fossa (pre-
ganglionic fibers), they enter the orbital cavity and
synapse on the ciliary ganglion and from there post-
ganglionic fibers reach the intrinsic muscle of the eye.

Rm normally the size of our pupils is controlled by a

balance in between sympathetic (coming from spinal
cord C8-T1 to L2-3 sympathetic pre-ganglionic
neurons which reach the dilator pupils) and para-
sympathetic activity. Size and activity of the pupils is
one of the first thing checked during a neurological
examination.

Lesions:
A lesion to either the oculomotor nerve fibers or the Edinger-Westfal nucleus will cause a
mono-lateral ipsilateral mydriasis and non consensual reflex. This is the case for example of an
herniation of the uncus, compressing the 3rd CN; the uncus is part para-hyppocampal gyrus and in
case of an increase of supra-tentorial pressure, this structure is the closest to the incisura tentori so it
tends too herniate.
A midbrain lesion to the pre tectal area (central lesion) will cause a bilateral loss of reflex.
A lesion to the pons instead will cause pinpoint pupils (myosis), which are still reactive to light
(the parasympathetic innervation is maintained in this case), this because in the tegmentum of the
pons runs a pathway going from the hypothalamus to the cilio-spinal centers of the spinal cord
which is important for dilating the pupil (so in case of a lesion, the spinal cord can’t receive stimuli
from the hypothalamus and this will result in a reduced sympathetic outflow to the dilator pupils).
The same happens in case of a diencephalon lesion (in this case the hypothalamus is directly
involved).The hypothalamus in fact directly receive retinal information (amount of light/darkness
information), which are important for circadian rhythm.
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 Corneal reflex
This is a consensual reflex, and requires:
•The pre tectal area of the brainstem
•The RF
•The trigeminal nerve 5th CN
•The facial nerve 7th CN

Afferent branch: light touch on the cornea cause activation of pain and
light touch receptor of the ophthalmic branch of the trigeminous, these
information are carried to the bulbs-spinal nucleus of trigeminous, and
from there to the RF

Efferent branch: from the RF to activate the orbicularis oculi (facial

muscle) there is signaling to the facial motor nucleus (in the pons).

Oculocephalic reflex or Doll’s eye

Normally if the head of a patient is rotated to one side, the eyes should go
to the other side in order to maintain the fixation point.
This can be used to test coma patient and understand if the brainstem is still
working, otherwise when the head is quickly but gently rotated to one side,
the eye follow the same direction remaining fixed in midpoint position.
To have this reflex there is the need of a functioning vestibular apparatus
and nuclei (four nuclei, superior, inferior, medial and lateral, partly in
rostral medulla, partly in caudal pons) , to detect head rotation, and an
efferent component made by horizontal gaze centers (PPRF paramedian
pontine RF) and oculomotor (midbrain) and abducens motor nuclei (pons), to control medial and
lateral recti of the eye.
Moreover to put in communication oculomotor centers in the midbrain with the other in the pons
there is a tiny bundle running medially in the brainstem tegmentum which is the medial
longitudinal funiculus
To have the same reflex but on the vertical plane we need instead a
vertical gaze center (in the pre-tectal area of midbrain, rostral
interstitial nucleus of the medial longitudinal funiculus and others:
nucleus of cajal and of Darkschewitsch).

FOCUS on MLF (medial longitudinal funiculus): is a paired white

matter tract running close to the midline and extending from the
midbrain to the upper cervical segment of the spinal cord. 

It is the final common pathway for different types of conjugate eye
movements like saccades (superior colliculi and pontine RF), smooth
pursuit (CN 3rd, gaze centers and cerebellum), vestibulocochlear reflex
(see below for details), and forms a communication between all the
ocular motor nuclei. Inside this bundle of fibers runs also the tecto-
spinal tract and part of the reticolo-spinal tract.

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Lesions of the MLF can be present in case of middle brainstem injury causing internuclear
ophthalmoplegia: inter-nuclear because as we said this bundle keep in
communication different nuclei for coordination of eye movements;
ophthalmoplegia instead come from the fact that there is a paralysis of
the eye movements and impaired horizontal conjugate eye movements
(the affected eye can’t move correctly on horizontal plane and the
contralateral eye present nystagmus). About a third of the cases of
internuclear ophthalmoplegia is caused by infarctions and are commonly
unilateral and seen in older individuals. Demyelinating disorders like
multiple sclerosis (MS) account for another third of cases and are mostly
bilateral and seen in young adults and adolescents.

Oculo vestibular reflex (caloric reflex test)

Neuroanatomical basis of reflex:

if the reflex is not working it can be
due to either a problem of the
sensory portion (vestibular
apparatus and nuclei), of the gaze
centers (PPRF), of the effector
component (CN 3rd and 6th) or of
the medial longitudinal funiculus
MLF.

Lesions:
•Vertical gaze center: rostral
interstitial nucleus of the medial
longitudinal fasciculus lesion: the patient present
vertical saccadic paresis so he has no vertical
saccadic eye movement
•PPRF: horizontal saccadic paresis, this occur
usually on one side so one eye can move
correctly while the other can not.
•Cerebellar floculo-nodular lobe: normally
receive direct input from the inner ear, mostly to
control eye movement, if a lesion occur here the
patient present with down beat nystagmus
(nystagmus is characterized by a slow phase and
a saccadic phase), in which there is a normal
slow phase and then during the saccadic
movement the eyes tend too go downward.

RM: in the spinal cord some reflexes can also be monosynaptic so without an intermediate synapse
there is a direct contact in between sensor and effector (simple reflex arch) instead for cranial
nerves all reflexes require an intermediate component which is the RF.

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Autonomic centers: micturition centers
Are involved in the control of urine storage in the bladder
and its contraction when needed for micturition, this centers
are two main and are in the pons:
•Pontine storage center
•Pontine micturition center
Lesions at the level of the pons can give impaired control
over this function, even if this is quite rare.

Orofacial movements
Mammalian face and mouth contain sophisticated motor plants that produce diverse oro-facial
behaviors (breathing, sniffing, chewing, swallowing, vocalizing, emotional facial expression as
smiling or crying… done mostly involuntarily).
The brainstem contains key neural circuits that drive and coordinate different cranial motoneurons
to produce various oro-facial actions (central patterns generator in RF); these centers are mostly
laterally in the pons and medullary tegmentum (region lateral to hypoglossal/ambiguus nuclei to
area surrounding facial nucleus up to trigeminal nucleus).

Lesions in the brainstem can produce a dystonia of oro-facial movements.

Consciousness
The RF, especially of the rostral part of the brainstem (midbrain and upper pons), contains the
ARAS, ascending reticular activating system, projection from the RF to the cortex (via thalamic
relay stations mostly as intra-laminar nuclei, basal forebrain and hypothalamus), involved in arousal
and maintenance of an active cortical function.
Lesions here may lead to a complete loss of consciousness or a reduced state of consciousness

Ascending pathways

Pathways in the brainstem

• Ascending pathways: tegmentum
• Oldest descending pathways: tegmentum
• Newest descending pathways: base or foot: cortico-spinal or pyramidal tract
and cortico pontine (neocortex – neocerebllum) Descending pathways

Lesions of the tegmentum of the brainstem besides causing problem

associated to CN nuclei and specific nuclei of the brainstem (relay nuclei), will
also cause sensory problems (ascending pathway) and motor problems (oldest
descending pathways, as posture defects if the reticulo-spinal tract get involved).
Lesions in the base of the brainstem instead mostly are associated to severe
voluntary motor loss (paralysis) due to damages at the cortico-spinal tract and ataxic problem (lack
of movements coordination) due to possible involvement of the cortico-pontine tract (connection to
cerebellum, even if, being already paralyzed the patient can’t be ataxic).

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Ascending pathway
Running in the tegmentum of the brainstem there are two main
somatosensory pathways projecting too the cerebral cortex (not only):
•Dorsal column medial-lemniscus pathway: originate from A-alpha
fibers (large diameter, myelinated fibers), which enter through the
medial division of the dorsal route, they run in the dorsal column of
white matter in the spinal cord, they synapse into the dorsal column
nuclei (gracile and cuneate, ventral medulla); from there, there is a
crossing of fibers, which then reach the contralateral thalamus and
after cortex. In the brainstem this pathway runs all through, medially
to reach the thalamus.
•Spino-thalamic tract: it’s part of the anterolateral system of the
spinal cord, it originates from A-delta and A-c fibers (slightly
myelinated middle and un-myelinated small size fibers), these cross
contra laterally in the spinal cord, and then run (already contra laterally) in the brainstem
(laterally in the tegmentum) to reach thalamus and then cortex.

Lesions to this pathways will cause major sensory loss, and according to the position of the lesion
medial (medial lemniscus involved) or lateral (spino-thalamic tract involved) there will be specific
sensory loss, even if; these two pathways get near one to the other going upward: in the medulla
are well separated but starting from the pons they get more near and in the midbrain are almost
attached one to the other. 

This is because this two pathways both project to the VPL ventro-postero-lateral nucleus of the
thalamus so they need to reach the same relay station to get to the
cortex (and moreover the medulla and pons due to embryological book
like opening are broader differently from the midbrain). Lesions in
the midbrain indeed are more probably involving both this pathways.

•Spino-cerebellar pathway
There are mainly two pathways bringing afferent information to the
cerebellum, these are:
•The dorsal (or posterior) spino-cerebellar tract: reach the cerebellum
via the inferior cerebellar peduncle (medulla)
•The ventral (anterior) spino-cerebellar tract: reach the cerebellum via
the superior cerebellar peduncle (midbrain)

They run quite laterally in the tegmentum of the brainstem (ventral is
purple in the pic, dorsal is red); these pathways carry information to
the cerebellum about proprioception/touch and from interneurons of
the spinal cord involved in movements control, so that in term the
cerebellum can organize movements accordingly.
Lesions of the lateral tegmentum would involve this path causing
ataxia (also because the dorsal tract pass through the inferior peduncle,
in which also vestibular information pass, and so if a lesion involve
this region there will be for sure problems in movements coordination,
equilibrium and maybe vertigo).
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