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Neuroscience
Week 4: Brainstem and cranial nerves

Learning Objectives

1. Diplopia

Diplopia is the perception of 2 images of a single object. Diplopia may be monocular or binocular.
Monocular diplopia is present when only one eye is open. Binocular diplopia disappears when either
eye is closed.

Most commonly, the eyes are misaligned because of a disorder affecting the cranial nerves innervating
the extraocular muscles (3rd, 4th, or 6th cranial nerves). These palsies may be isolated and idiopathic
or the result of various disorders involving the cranial nerve nuclei or the infranuclear nerve or nerves.
Whether pain is present depends on the disorder. Other causes involve mechanical interference with
ocular motion (which often cause pain) or a generalized disorder of neuromuscular transmission (which
typically do not cause pain).

Double vision is a complaint that can bring a dull, sick feeling to an optometrist’s stomach. Diplopia can
develop from a host of pathologies including dry eye, cranial nerve (CN) palsies and retinal issues. When
patients present with a CN palsy causing double vision, optometrists are tasked with isolating which nerve
or nerves are involved and, ultimately, the underlying cause. 

Anatomy
Cranial nerves III, IV and VI control our extraocular muscles and each plays a specific role in the
movement of our eyes. CN IV controls our superior oblique muscles, which control intorsion, depression
and abduction.2,3 Loss of this muscle’s function causes an upward deviation of the affected eye with a
cyclotorsion that causes the patient to tilt their head away from the lesion.2,3 This is the most common
cause of acquired vertical diplopia that is worse on downgaze.4 CN VI controls our lateral rectus muscle,
which controls abduction.5With loss of innervation to this muscle, we are unable to turn the eye away from
the midline and patients will often turn their head to avoid double vision. 

This leaves CN III to control all the other extraocular muscles and, when affected, tends to be the most
dramatic, leaving the eye in a “down and out” position.5 CN III also controls the innervation of the levator
muscle, which, if paralyzed, may also result in ptosis.5 The parasympathetic pupillary constricting fibers
travel along the external portion of the CN III, which may be affected during a compressive lesion or
aneurysm.3 An APD can be a sign of an aneurysm, which is emergent.3

When any one of these three cranial nerves is palsied it can result in diplopia, and the nerve experiencing
the palsy should be identified.2-4,6 With CN III palsy, it is extremely important to monitor for pupillary
involvement at the time of the exam and in the coming weeks thereafter. 

Causes
Studies show that the most prevalent ocular CN palsy is that of CN VI, followed by CN III and then CN IV.
The most common cause of acquired palsy in all three is ischemic changes from vascular diseases
including diabetes, hypertension and atherosclerosis.

Mass lesions both in the orbit and in the brain are likely causes as well for CN III, IV and VI palsies.
Depending on the location, a lesion or aneurysm on CN III can cause pupillary involvement. 

Trauma is the third most common cause of these ocular palsies, with a higher occurrence of CN IV palsies
related to the long distance it covers inside the cranial vault.

Although not common, research shows a CN VI palsy can occur with giant cell arteritis (GCA).13 

2. Lateral vision
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Abducens nerve (CN VI)

The abducens nerve innervates the lateral rectus muscle of the eye. It is responsible for lateral eye
movements. Injury to this nerve prevents such movement. Injury to this nerve can cause double vision.
Owing to its lengthy nature, multiple areas of the nerve have the potential to be damaged, whether at its
nucleus or along cranial bone areas. It is difficult to locate the area of damage. But if this nerve is
damaged, other cranial nerves are frequently also injured.18 Injury to this nerve occurs at a rate of 0.4%–
4.1%.

Neuroanatomy
The brain exerts ultimate control over both voluntary and involuntary eye movement. Three cranial
nerves carry signals from the brain to control the extraocular muscles. These are the oculomotor nerve,
which controls the majority of the muscles, the trochlear nerve, which controls the superior oblique muscle,
and the abducens nerve, which controls the lateral rectus muscle.
In addition to the movement of muscles, numerous areas in the brain contribute to involuntary and
voluntary eye movement. These include providing the conscious perception of vision, as well as areas
that facilitate tracking.
 Brain
o Cerebral cortex
 Frontal lobe – frontal eye fields (FEF), medial eye fields (MEF), supplementary eye
fields(SEF), dorsomedial frontal cortex (DMFC)
 Parietal lobe – lateral intraparietal area (LIP), middle temporal area (MT), medial
superior temporal area (MST)
 Occipital lobe
 Visual cortex
o Cerebellum[7]
 Midbrain
o Pretectal area – Pretectal nuclei
o Superior colliculus (SC)
o Premotor nuclei in the reticular formation (PMN)
 riMLF
o III, IV cranial nerve nuclei
 Pons
o Paramedian pontine reticular formation (PMRF)
o Nucleus prepositus hypoglossi
o Vestibular nuclei
o VI cranial nerve nuclei
 Medial longitudinal fasciculus

3. Bell’s palsy

Facial nerve palsy

Facial (nerve) palsy is a neurological condition in which function of the facial nerve (cranial nerve VII) is
partially or completely lost. It is often idiopathic but in some cases, specific causes such as trauma,
infections, or metabolic disorders can be identified. Two major types are distinguished: central facial
palsy (lesion occurs between cortex and nuclei in the brainstem) and peripheral facial palsy (lesion occurs
between nuclei in the brainstem and peripheral organs). Central facial palsy manifests with impairment of
the lower contralateral mimic musculature. In contrast, peripheral facial palsy leads to impairment of
the ipsilateral mimic muscles and also affects the eyelids and forehead. Additionally, peripheral facial
palsy can cause various sensory and autonomic disorders (depending on the exact location of the lesion).
Diagnosis can usually be made clinically while patient history often helps in evaluating the underlying
etiology. Idiopathic facial nerve palsy is treated with oral glucocorticoids and, in severe cases, antivirals.
Treatment of the other types depends on the underlying cause. Most cases of idiopathic facial palsy heal
completely within 3 weeks.
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Etiology 
 Idiopathic (50% of cases): acute idiopathic peripheral facial palsy is also known as Bell palsy
 Secondary 
o Trauma (e.g., temporal bone fracture)
o Infection (e.g., herpes zoster, borreliosis, HSV infection, HIV infection)
o Tumors
o Pregnancy
o Diabetes mellitus
o Guillain-Barré syndrome
o Sarcoidosis
o Amyloidosis
o Stroke

Pathophysiology 
 The muscles responsible for eyelid and forehead movements are innervated by fibers from both
sides
o Central facial palsy: unilateral lesion between cortex and brainstem nuclei → muscles of
the eyelids and forehead are still supplied by input from the other side → function
is preserved
o Peripheral facial palsy: unilateral lesion between nuclei and muscles → no input to
the ipsilateral eyelid and forehead muscles → paralysis
 The lower facial muscles are only innervated by fibers from
the contralateral hemisphere (via ipsilateral nuclei and the ipsilateral peripheral nerve) →
paralyzed in both central and peripheral facial palsy

Clinical features 

Additional signs of peripheral facial palsy

 Sensory disturbances (painful sensation around or behind the ear or numbness of one side of the
face, taste disorders , hyperacusis)
 Dry mouth (as a result of decreased saliva production) 
 Ocular features (lagophthalmos , decreased lacrimation , ectropion )
 Synkinetic involuntary movements of the facial muscles (e.g., facial spasms while closing the
eyes) 
*In central facial palsy, paralysis is contralateral to the lesion and eyelid and forehead muscles are not
affected!
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Diagnostics 
 Ask about symptom onset and duration, recent infections, and outdoor trips
 Ask patient to perform facial movements (e.g., frown, whistle, inflate cheeks, smile,
show teeth/grimace, close eyes tightly , blink) → observe inabilities and asymmetries
o Bell's phenomenon

Treatment 
 Prednisone
 In severe cases 
o Valacyclovir for 1 week
o Eye care with, e.g., artificial tears
 Traumatic facial nerve palsy: surgical decompression or nerve repair

Prognosis 
 Idiopathic facial palsy: complete recovery in ∼ 85% of cases (within 3 weeks)
 Misdirected regrowth of nerve fibers can lead to persistent disorders(e.g., synkinesias)
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Facial weakness or paralysis may result either from (I) a peripheral lesion of CN VII, the facial nerve,
anywhere from its origin in the pons to its periphery in the face, or (2) a central lesion involving the upper
motor neuron system between the cortex and the pons.
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The lower part of the face normally is controlled by upper motor neurons located on only one side of the
cortex—the opposite side.
Left hemispheric damage to these pathways, as in a stroke, paralyzes the right lower fate. The upper face,
however, is controlled by pathways
from both sides of the cortex. Even though the upper motor neurons on the left are destroyed, others on
the right remain, and the right upper face continues to function fairly well.

4. Uvula (Cranial Nerve)

IX, X. Glossopharyngeal and Vagus Nerves

These two nerves are considered together because they exit from the brain stem side by side, and have
similar and frequently side-by-side and overlapping functional and anatomical distributions in the periphery.
Also, these nerves connect with many of the same brain stem nuclei (dorsal motor nucleus of the vagus,
nucleus ambiguus, nucleus solitarius, spinal nucleus of the trigeminal) and are often damaged together.

Pharynx and palate

The pharynx is innervated by nerves IX and X, with motor and sensory contributions from both. In general,
the vagus nerve is motor to the palate elevators and constrictors of the pharynx (as occurs in swallowing
and gagging). The glossopharyngeal contains more sensory fibers, including from the posterior part of the
tongue and pharynx down to the level of the larynx (where the vagus nerve begins to take over). The entire
palate, including the soft palate, has a sensory distribution from the maxillary division of the trigeminal
nerve. 
Contraction of the paired and fused muscles of both sides of the soft palate causes superolateral
movement vectors (Fig. 7-1). The sum vector is an upward, midline movement of the palate to seal the
nasopharynx when swallowing and making certain sounds (such as "guh"). When examining palate
elevation, look at the point of attachment of the uvula to see if it remains in the midline. Also, if there is
deviation, inspect the palate to make sure this is not simply due to scaring of the soft palate due to prior
throat surgery. If the vagus nerve of one side is damaged (e.g., by a tumor at the jugular foramen), the
palate elevates asymmetrically, being pulled up toward the strong side (i.e., away from the weak side of the
palate, Fig. 7-2).
If both sides of the palate are weak, as can occur in certain muscle diseases or if the vagus is
damaged bilaterally (such as from invasion by a retropharyngeal carcinoma at the base of the skull), the
palate does not elevate normally during phonation and a hypernasal quality is imparted to the voice
(especially noted when making a "G" sound). Air usually emanates from the nose when the patient tries to
puff up the cheeks and liquid tends to regurgitate into the nose when swallowing. Rarely, a similar finding
of bilateral weakness can be seen in patients with bilateral supranuclear lesions (such as by bilateral
cortical damage or bilateral damage to the corticobulbar tracts). In this case, the patient will often show
signs of "pseudobulbar" affect.

Cranial nerve X – Vagus nerve

The vagus nerve contains visceral efferent and afferent fibers and innervates the head, neck, thorax, and
abdomen.3 The efferent motor fibers of the vagus nerve supply all striated muscles of the larynx and
pharyx, except the stylopharyngeus (supplied by IX) and the tensor veli palatini (supplied by V3). Motor
fibers leave the vagus nerve as three main branches.1 The pharyngeal branch travels between the internal
and external carotid arteries and enters the pharynx at the upper border of the middle constrictor muscle,
supplying levator veli palatini, salpingopharyngeus, palatopharyngeus and the uvula.3 Palatoglossus is the
only striated tongue muscle innervated by the vagus nerve and acts to elevate the posterior portion of the
tongue.4 The superior laryngeal nerve branches distal to the pharyngeal branch and descends lateral to the
pharynx. The external branch of the superior laryngeal nerve supplies motor innervation to the cricothyroid
muscle. The third motor branch off the vagus nerve is the recurrent laryngeal nerve. The right recurrent
laryngeal nerve descends anterior to the subclavian artery, then turns posteriorly under the artery. The left
recurrent laryngeal nerve turns posteriorly around the aortic arch and ascends through the superior
mediastinum. The two then return to the base of the neck and travel superiorly in their respective
tracheoesophageal grooves.5 Both recurrent branches enter the larynx below the inferior constrictor and
supply all intrinsic muscles of larynx excluding the cricothyroid muscle (supplied by the external branch of
the superior laryngeal nerve).
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The vagus nerve receives sensory input from the larynx, pharynx, external auditory canal, lateral aspect of
the tympanic membrane, and the meninges of the posterior fossa.6 Subglottic sensation is mediated by the
recurrent laryngeal nerve, whereas the internal branch of the superior laryngeal nerve mediates sensation
from the supraglottis. Glottic sensation likely involves both nerves. The vagus nerve also receives general
visceral afferent information from the trachea, bronchi, lungs, heart, aortic arch, esophagus, and abdominal
viscera.3 The vagus nerve also supplies parasympathetic innervation to smooth muscle and glands of the
pharynx, larynx, and thoracic and abdominal viscera.

Associated
Nerve(s) Function(s) Evaluation(s)
conditions
 Gag response
 Visualizing uvula deviation
IX and Taste, away from affected side on
Lateral medullary
X: Glossopharyngeal pharyngeal articulating "AHH" with tongue
syndrome(IX)
and Vagus movement depressor.
 Palatal articulation "KA"
 Guttural articulation "GO"

5. Brainstem and Cerebellum Function

Brainstem Function
The brainstem has many basic functions, including regulation of heart rate, breathing, sleeping, and eating.
It also plays a role in conduction. All information relayed from the body to the cerebrum and cerebellum
and vice versa must traverse the brainstem. The ascending pathways from the body to the brain are the
sensory pathways, including the spinothalamic tract for pain and temperature sensation and the dorsal
column, fasciculus gracilis, and cuneatus for touch, proprioception, and pressure sensation. The facial
sensations have similar pathways and also travel in the spinothalamic tract and the medial lemniscus.
Descending tracts are upper motor neurons destined to synapse on lower motor neurons in the ventral
horn and intermediate horn of the spinal cord. In addition, upper motor neurons originate in the brain
stem’s vestibular, red, tectal, and reticular nuclei, which also descend and synapse in the spinal cord. The
brainstem also has integrative functions, including cardiovascular system control, respiratory control, pain
sensitivity control, alertness, awareness, and consciousness.

The brainstem has three broad functions: 

1. Serves as a conduit for the ascending tracts and descending tracts connecting the spinal cord to the
different parts of the higher centres in the forebrain 
2. Contains important reflex centres associated with the control of: 
 respiration 
 cardiovascular system 
 consciousness
3. Contains the nuclei of Cranial Nerves III to XII. 

The brain stem is responsible for, and regulatory of, the following functions of the human body: 
 Alertness 
 Attention 
 Arousal 
 Breathing 
 Heart rate 
 Blood pressure 
 Conveys information and signals shared between the peripheral nerves and spinal cord to the
upper brain 
 Other autonomic functions such as digestion, salivation, perspiration, dilation or contraction of the
pupils, urination, etc.
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Cerebellum Function
The cerebellum is a structure that is located at the back of the brain, underlying the occipital and temporal
lobes of the cerebral cortex. Although the cerebellum accounts for approximately 10% of the brain’s
volume, it contains over 50% of the total number of neurons in the brain. Historically, the cerebellum has
been considered a motor structure, because cerebellar damage leads to impairments in motor control and
posture and because the majority of the cerebellum’s outputs are to parts of the motor system. Motor
commands are not initiated in the cerebellum; rather, the cerebellum modifies the motor commands of the
descending pathways to make movements more adaptive and accurate. The cerebellum is involved in the
following functions:
Maintenance of balance and posture. The cerebellum is important for making postural adjustments in
order to maintain balance. Through its input from vestibular receptors and proprioceptors, it modulates
commands to motor neurons to compensate for shifts in body position or changes in load upon muscles.
Patients with cerebellar damage suffer from balance disorders, and they often develop stereotyped
postural strategies to compensate for this problem (e.g., a wide-based stance).
Coordination of voluntary movements. Most movements are composed of a number of different muscle
groups acting together in a temporally coordinated fashion. One major function of the cerebellum is to
coordinate the timing and force of these different muscle groups to produce fluid limb or body movements.
Motor learning. The cerebellum is important for motor learning. The cerebellum plays a major role in
adapting and fine-tuning motor programs to make accurate movements through a trial-and-error process
(e.g., learning to hit a baseball). 
Cognitive functions. Although the cerebellum is most understood in terms of its contributions to motor
control, it is also involved in certain cognitive functions, such as language. Thus, like the basal ganglia, the
cerebellum is historically considered as part of the motor system, but its functions extend beyond motor
control in ways that are not yet well understood.

Function by regions
 The cortex of the vermis coordinates the movements of the trunk, including the neck, shoulders, thorax,
abdomen, and hips. 
 Control of the distal extremity muscles is by the intermediate zone of cerebellar hemispheres, located
adjacent to the vermis. 
 The remaining lateral area of each cerebellar hemisphere provides the planning of sequential
movements of the entire body along with involvement in the conscious assessment of movement errors
 The cerebellum is essential for making fine adjustments to motor actions. Cerebellar dysfunction
primarily results in problems with motor control.
 Four principles are important to cerebellar processing: feedforward processing, divergence and
convergence, modularity, and plasticity.
 Signal processing in the cerebellum is almost entirely feedforward. Signals move through the system
from input to output with very little internal transmission.
 The cerebellum both receives input and transmits output via a limited number of cells.
 The cerebellar system is divided into thousands of independent modules with similar structure.
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6. Extra-axial vs. intra-axial lesions

What is Extracranial Cerebrovascular Disease?

The brain receives its blood supply from two sets of arteries. 
The carotid arteries travel up the front of the neck and supply blood to the front part of the brain where
important functions are located, including:
 Speech
 Personality
 Thinking
 Sensory
 Motor functions 
The vertebral arteries run through the spine and supply blood to the back of the brain (brainstem and
cerebellum).  
When any of these arteries are narrowed or blocked, it creates a condition called stenosis that drastically
increases the risk of stroke, aneurysm, and other neurovascular disorders
What is extracranial/intracranial vascular disease?
Extracranial vascular disease refers to carotid or vertebral stenosis outside the skull.
Intracranial vascular disease involves the arteries within the skull or at the base of the skull.
Atherosclerosis, the hardening and narrowing of the walls of these vessels due to deposits of fats that form
plaques within the arteries, is the most common cause of extracranial and intracranial vascular disease. As
the plaque deposits gradually enlarge, they interfere with blood flow.
Atherosclerosis can affect any large-to-medium-sized artery in the body and cause serious health
problems.
In rare cases, the narrowing of carotid arteries can be caused by other conditions such as:
 Marfan syndrome
 Fibromuscular dysplasia
 Other disorders
One type of intracranial vascular disease is moyamoya disease, the narrowing and ultimate closure of the
internal carotid arteries, which has its own symptoms and recommended treatments. 
At UPMC, extracranial and intracranial vascular disease may be treated medically or surgically, depending
upon the severity of the disease.

Diagnosing Extracranial/Intracranial Vascular Disease

To diagnose extracranial vascular disease, your doctor will:
 Perform a full physical exam
 Ask about your medical and family history
 Perform several imaging tests
Testing to diagnose extracranial/Intracranial vascular disease
Your doctor may request imaging tests to examine how blood flows through your arteries. These diagnostic
tests include:
 Arteriograms or angiography using x-rays
 Doppler test
 Magnetic resonance arteriography (MRA), a type of MRI scan
 CT angiography

Extracranial/Intracranial vascular disease symptoms

Symptoms vary depending on whether carotid or vertebral arteries are affected. 
Carotid stenosis generally shows no symptoms until a complication occurs, such as a stroke or brain
aneurysm occurs. However, some people experience warning symptoms of a stroke called a transient
ischemic attack (TIA), which should be treated as a medical emergency, even if the symptoms go away. 

Symptoms of transient ischemic attacks (TIA)

TIAs are often warning signs of an imminent stroke. 
Symptoms of a TIA include:
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 Weakness or numbness on one side of the body

 Difficulty speaking or understanding speech
 Sudden, severe headache
 Changes in vision

Vertebral artery disease symptoms

Symptoms of vertebral artery disease overlap with those of carotid artery disease and may include:
 Dizziness
 Vertigo
 Double vision
 Numbness around the mouth
 Tinnitus (ringing in the ears)
 Difficulty speaking
 Partial blindness

Extracranial/Intracranial Vascular Disease Treatments

In cooperation with neurologists, cardiologists, and radiologists, UPMC’s neurovascular doctors take a
multidisciplinary approach to recommend treatments that are least disruptive to a person's brain, critical
nerves, and offer the ability to return to normal functioning.
Treatment for extracranial and intracranial vascular disease depends upon:
 Location of the problem
 Severity of symptoms
 Person's age and medical history

Medication and lifestyle changes

Extracranial and intracranial vascular disease can sometimes be prevented, though not reversed, by
several lifestyle changes. To address atherosclerosis, people may be advised to:
 Quit smoking
 Eat a low-fat and low-cholesterol diet
 Exercise
 Lose weight
This can help lower blood pressure and cholesterol, which in turn can slow the buildup of plaque in the
arteries. 
Along with lifestyle changes, medications are usually the most frequently recommended treatment.
Common prescriptions include:
 Drugs that lower cholesterol and blood pressure
 Antiplatelet and anticoagulant drugs to prevent blood clots from forming

Carotid endarterectomy
When stenosis severely restricts an artery, or a person has already suffered a stroke, an open surgical
approach may be indicated. 
A carotid endarterectomy consists of a small linear incision in the neck followed by dissection and
localization of the carotid artery. 
The artery is opened and all the “calcified fat” (atheroma) is removed from the artery to:
 Re-establish blood flow 
 Reduce chance of strokes 
Brain waves are monitored during surgery to make sure the brain is receiving enough blood throughout the
procedure.

Angioplasty and stenting

Angioplasty involves inserting a thin tube called a catheter into an artery in the groin or leg and threading
the catheter up to the affected artery 
A small balloon at the end of the catheter is inflated at the blocked area, flattening the plaque buildup
against the artery wall and widening the artery so blood flow is restored. 
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The procedure may be followed by stenting, which inserts a wire mesh tube called a stent into the artery to
hold it open in the long term.

7. Fossa posterior
The floor of the cranial cavity is divided into three distinct depressions. They are known as the anterior
cranial fossa, middle cranial fossa and posterior cranial fossa. Each fossa accommodates a different part
of the brain.
The posterior cranial fossa is the most posterior and deep of the three cranial fossae. It accommodates the
brainstem and cerebellum.

Borders
The posterior cranial fossa is comprised of three bones: the occipital bone and the two temporal bones.
It is bounded as follows:
 Anteriorly and medially it is bounded by the dorsum sellae of the sphenoid bone. This is a large
superior projection of bone that arises from the body of the sphenoid.
 Anteriorly and laterally it is bounded by the superior border of the petrous part of the temporal bone.
 Posteriorly it is bounded by the internal surface of the squamous part of the occipital bone.
 The floor consists of the mastoid part of the temporal bone and the squamous, condylar and basilar
parts of the occipital bone.

The bones of the cranial floor. The posterior cranial fossa has been outlined.

Contents
The posterior cranial fossa houses the brainstem and cerebellum.
The brainstem is comprised of the medulla oblongata, pons and midbrain and continues down through
the foramen magnum to become the spinal cord. The cerebellum has an important role in co-ordination
and fine motor control.
Alongside the gross anatomical structures of the brainstem and cerebellum, the posterior cranial fossa also
accommodates associated arteries and nerves. Some key structures will be discussed with regards to their
foramina below.

Foramina
There are several bony landmarks and foramina present in the posterior cranial fossa (a foramen is simply
a hole that allows the passage of a structure – usually a blood vessel or nerve).

Temporal Bone
The internal acoustic meatus is an oval opening in the posterior aspect of the petrous part of the
temporal bone. It transmits the facial nerve (CN VII), vestibulocochlear nerve (CN VIII) and labyrinthine
artery.
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Occipital Bone
A large opening, the foramen magnum, lies centrally in the floor of the posterior cranial fossa. It is the
largest foramen in the skull. It transmits the medulla of the brain, meninges, vertebral arteries, spinal
accessory nerve(ascending), dural veins and anterior and posterior spinal arteries. Anteriorly an incline,
known as the clivus, connects the foramen magnum with the dorsum sellae.
The jugular foramina are situated either side of the foramen magnum. Each transmits
the glossopharyngeal nerve, vagus nerve, spinal accessory nerve(descending), internal jugular vein,
inferior petrosal sinus, sigmoid sinus and meningeal branches of the ascending pharyngeal and occipital
arteries.
Immediately superior to the anterolateral margin of the foramen magnum is the hypoglossal canal.
It transmits the hypoglossal nerve through the occipital bone.
Posterolaterally to the foramen magnum lies the cerebellar fossae. These are bilateral depressions that
house the cerebellum. They are divided medially by a ridge of bone, the internal occipital crest.

The bony landmarks and foramina of the posterior cranial fossa.

8. Brain imaging (pons, midbrain, sella, temporal)

9. Meningioma and Schwannoma (classification, grading system, correlation with pregnancy)

Brain tumors
Brain tumors are masses of abnormal cells within the brain. They can be primary or metastatic, benign or
malignant. Common tumors in children are pilocytic astrocytomas, medulloblastomas, ependymomas,
and craniopharyngiomas. Adults most often develop glioblastoma
multiforme, meningiomas, hemangioblastomas, schwannomas, oligodendrogliomas, and pituitary
adenomas. Clinical features and radiological findings vary according to the type, location, and onset of
the tumor. Magnetic resonance imaging (MRI) is the primary diagnostic method. Removal of the
entire tumor is a prerequisite for remission. The histological grade of the tumor, which is determined
postoperatively, is an important factor in determining the prognosis. Malignant tumors usually require
additional treatment with radiotherapy and/or chemotherapy.
Astrocytomas (e.g., pilocytic astrocytoma, glioblastoma multiforme), meningiomas, pituitary adenomas,
and schwannomas are discussed in separate articles.
 Primary brain tumors arise within the CNS
 Metastasis
o Drop metastases and leptomeningeal metastases can occur. 
 Typically present as nodules along the spine and cauda equina that can cause
back pain with neurologic symptoms (e.g., limb weakness).
 Can be detected by lumbar puncture.
o Primary CNS tumors do not metastasize to organs outside the CNS.

Adult primary brain tumors

 Primary brain tumors are less common than brain metastases in adults. 
o Most common benign primary brain tumor in adults: meningioma
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o Most common malignant primary brain tumor in adults: glioblastoma multiforme

 Primary brain tumors account for approx. 2% of cancer cases in adults 
In adults, most primary brain tumors arise supratentorially, hemangioblastomas and schwannomas being
important exceptions!

Meningioma
Meningiomas are almost always benign, slow-growing brain tumors that arise from arachnoid cap cells of
the arachnoid villi. As meningiomas may remain asymptomatic for long periods of time, they are often an
incidental finding. Tumor compression can lead to a wide variety of neurological symptoms
(i.e., headaches, seizures, parasthesias) that are generally specific to the structure(s) being compromised.
Contrast imaging typically shows an enhanced round tumor with well-defined margins that often resembles
a snowball. Management depends on the location and grade of the tumor, as well as patient-
specific factors such as age, comorbidities, and accompanying symptoms. Treatment generally consists of
surgical intervention, radiotherapy, or a combination of both. In some cases (e.g., asymptomatic elderly
patients, or those with slow-growing meningiomas), a "watch and wait" approach with
regular tumor monitoring may be safer than invasive therapy.
Meningiomas are a diverse group of brain tumors that arise from the arachnoid layer (specifically the
arachnoid cap cells) and can therefore occur in any part of the CNS with a meningeal covering.

Epidemiology 
 Most common primary brain tumor in adults
 Sex: ♀ > ♂ (3:2) 
 Peak incidence: patients in their 60's

Etiology 
 Mostly idiopathic
 Exposure to ionizing radiation: Radiotherapy for head and neck tumors, dental x-rays
 Multiple meningiomas may develop in patients with type II neurofibromatosis.

Clinical features 
 General clinical features
o Mostly asymptomatic
o General symptoms of CNS tumors (e.g., seizures)
 Features related to tumor location
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o Falx cerebri (25% of cases): paraparesis (initially presents with foot drop) and uncontrolled

micturition
o Supratentorial convex surface (20% of cases): headache, seizures, neurological deficits
o Sphenoidal wings (20% of cases): visual defects, hypesthesia of the face (see superior
orbital fissure syndrome, orbital apex syndrome, and cavernous sinus syndrome) 
o Olfactory groove (10% of cases): anosmia, visual defects (see olfactory
groove syndrome, Foster-Kennedy syndrome) 
o Posterior crania fossa (10% of cases): sensorineural hearing loss, facial nerve
palsy (see cerebellopontine angle syndrome) 
o Intraventricular (2% of cases): headache, papilledema (see obstructive hydrocephalus) 
o Spinal meningioma (2% of cases): back pain, paraplegia (see cord transection syndromes)
o Foramen magnum (2% of cases)
 Early: specific pattern of sensory and motor deficits(unilateral upper extremity
→ ipsilateral lower extremity → contralateral lower extremity → contralateral upper
extremity)
 Late: spastic quadriparesis and lower cranial nerve palsiesleading
to atrophy and fasciculations (e.g., of the sternocleidomastoid muscle, the trapezius
muscle, and the tongue)

Diagnostics 
 MRI: Imaging modality of choice
o Plain MRI findings 
 Round, sharply demarcated space-occupying lesion(resembling a
snowball) with radiological features of an extra-axial tumor
 T1 → isointense ; T2 → isointense or hyperintense
 Dural tail sign
o Contrast MRI findings 
 Significant enhancement of the meningioma
 Sunburst appearance
 Spinal meningioma: ginkgo-leaf sign . 
 CT: hyperdense lesion, sometimes calcified
 Brain tumor biopsy: may be indicated if the tumor is inoperable or imaging is inconclusive.

Left: [Cerebral convexity meningioma] T1-weight sagittal MRI image: homogenous contrast enhancement
of a meningioma.
Right: T1-weighted sagittal MRI scan: evidence of a sharply demarcated, hyperintense lesion in the
olfactory groove. Suspected diagnosis: meningioma.

Pathology 
 Gross findings
o Encapsulated, round, grayish-white tumor
o Firm to hard consistency
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o Cross-sectional surface: gray, granular

 Microscopic findings
o Mesenchymal origin (arachnoid cap cells)
o Onion peel arrangement of tumor cells
o Psammoma bodies
o Increased vascularity 
o Most meningiomas are benign (WHO grade I) tumors
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Treatment 
 Surgical resection: first line treatment
 Radiotherapy
o In the case of inoperable tumors 
o Postoperatively, if the tumor was incompletely resected
o As an adjuvant therapy in the case of all grade II and III meningiomas 
 Active surveillance: consider in a slow-growing asymptomatic tumor in an elderly patient

Prognosis 
 WHO Grade I: good prognosis (recurrence rate ∼20%)

Meningiomas
Meningiomas are the most common benign intracranial tumor. They originate from arachnoid cap cells,
which are cells within the thin, spider web-like membrane that covers the brain and spinal cord. The
arachnoid is one of three protective layers, collectively known as the meninges, which surround the brain
and the spinal cord. The other two layers of the meninges are the dura mater and pia mater. Although the
majority of meningiomas are benign, these tumors can grow slowly until they are very large, if left
undiscovered, and, in some locations, can be severely disabling and life-threatening. Other forms of
meningioma may be more aggressive. Most patients develop a single meningioma; however, some
patients may develop several tumors growing simultaneously in other locations of the brain or spinal cord.
Some meningiomas are found along the dural lining in the venous sinuses of the brain and skull base –
locations where arachnoid cap cells are most abundant. The following subtypes are based on the location
of the tumor.
 Cavernous Sinus Meningioma: Occurs near the area that drains deoxygenated blood to the heart from
the brain.
 Cerebellopontine Angle Meningioma: Located near the margin of the cerebellum; acoustic
neuromas (vestibular schwannoma) are also frequently found in this area.
 Cerebral Convexity Meningioma: Located on the upper surface of the cerebral convexity.
 Foramen Magnum Meningioma: Located near the opening at the base of the skull through which the
lower portion of the brainstem passes.
 Intraorbital Meningioma: Located in or around the eye sockets.
 Intraventricular Meningioma: Located in the fluid chambers that produce and carry cerebrospinal
fluid throughout the brain.
 Olfactory Groove Meningioma: Located along the nerves connecting the nose to the brain.
 Parasagittal/Falx Meningioma: Located adjacent to the dural fold that separates the two brain
hemispheres.
 Petrous Ridge Meningioma: Portion of the temporal bone (which supports the temple) that contain
sections of the organs that facilitate hearing.
 Posterior Fossa Meningioma: Occurs near the back of the brain.
 Sphenoid Meningioma: Located near the sphenoid bone behind the eyes.
 Spinal Meningioma: Located in the spine, in some cases against the spinal cord.
 Suprasellar Meningioma: Located near the area of the skull where the pituitary gland is found.
 Tentorium Meningioma: Located near where the brain connects to the brainstem, an area known as the
tentorium cerebelli.

Types and Classification

The World Health Organization (WHO) classification of brain tumors is the most widely utilized tool in
grading tumor types. The WHO classification scheme recognizes 15 variations of meningiomas according
to their cell type as seen under a microscope. These variations are called meningioma subtypes – the
technical term for these cell variations is histological subtypes. These histological subtypes are organized
into three grades that generally reflects the rate of growth and likelihood of recurrence based on cytological
features. 

World Health Organization (WHO) Meningioma Classifications

WHO Grade I WHO Grade II WHO Grade III
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Benign Atypical Malignant

Meningiothelial Chordoid Papillary
Fibrous (fibroblastic) Clear Cell Rhabdoid
Transitional (mixed) Atypical Anaplastic
Psammomatous
Angiomatous
Microcystic
Secretory
Lymphoplasmacyte-rich
Metaplastic

Atypical meningiomas (WHO grade II, which account for 18% of meningioma cases) exhibit increased
tissue and cell abnormalities. These tumors grow at a faster rate than benign meningiomas and are often
characterized by brain invasion. Atypical meningiomas have a higher likelihood of recurrence than benign
meningiomas (WHO grade I).
Malignant meningiomas (WHO grade III) show increased cellular abnormalities and grow at a faster rate
than benign and atypical meningiomas. Malignant meningiomas are the most likely to invade the brain and
recur more frequently than the other two subtypes.

Prevalence and Incidence

According to the Central Brain Tumor Registry of the United States Statistical Report, of tumors diagnosed
in the U.S. in 2012-2016, meningiomas were the most frequently reported overall histology (37.6%) of all
primary central nervous system tumors with 33,560 cases projected in 2019. The average annual age-
adjusted incidence rate was also highest for meningiomas (8.6 per 100,000 people) of all primary brain and
spinal cord tumors. Additionally, these incidence rates for meningioma were observed to increase with age,
with a median age at diagnosis of 66 years. The majority of meningiomas with tissue confirmation are non-
malignant, with 1.7% confirmed to be malignant (WHO grade III). 

Risk Factors
The risk of meningioma increases with age with a dramatic increase after 65 years. Children aged 0-14 are
at the lowest risk. African Americans have been observed to have higher rates of meningioma than other
ethnic groups in the U.S. 
Exposure to ionizing radiation, especially high doses, has been associated with a higher incidence of
intracranial tumors, particularly meningiomas. There is also evidence indicating a connection between
meningiomas and low doses of radiation. The most well-known case involves children in Israel who were
given radiation for scale ringworm between 1948 and 1960. Within the U.S., dental X-rays are the most
common form of exposure to ionizing radiation. A number of studies have linked the number of full
mouth dental radiographs to increased risk of meningioma.
The genetic disorder Neurofibromatosis type 2 (NF2) is believed to put people at a higher risk of
developing meningioma. Patients with NF2 also may be more likely to develop malignant or multiple
meningiomas. 
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Per the Brain Science Foundation, a number of studies have suggested a correlation between
meningiomas and hormones, such as the following:
 Increased occurrence of meningioma in post-pubertal women compared with men. 
 A higher female to male incidence ratio during reproductive years that disappears with increasing age. 
 The detection of estrogen, progesterone and androgen receptors in a significant number of
meningiomas.
 A link between breast cancer and meningioma.
 A connection between meningioma growth, menstrual cycles and pregnancy.
Researchers are beginning to explore the possible connection between meningioma risk and the use of
oral contraceptives and hormone-replacement therapy procedures. 
Furthermore, an association between obesity and meningioma incidence in several large studiesindicates
a possible underlying relationship.
Symptoms
Because meningiomas commonly are slow-growing tumors, they often do not cause noticeable symptoms
until they are quite large. Some meningiomas may remain asymptomatic for a patient's lifetime or be
detected unexpectedly when a patient has a brain scan for unrelated symptoms. Presenting signs and
symptoms depend on the size and location of the tumor. Symptoms of meningiomas may include:
 Headaches
 Seizures
 Change in personality or behavior
 Progressive focal neurologic deficit
 Confusion
 Drowsiness
 Hearing loss or ringing in the ears
 Muscle weakness
 Nausea or vomiting
 Visual disorders
Symptoms can be related more specifically to the location of the meningioma. Examples include:
 Falx and Parasagittal: Impaired levels of brain functioning, such as in reasoning and memory. If
located in the middle section, it would likely cause leg weakness/numbness or seizures.
 Convexity: May cause seizures, headaches and neurological deficits.
 Sphenoid: Vision problems, loss of sensation in the face or facial numbness and seizures.
 Olfactory Groove: Loss of smell due to compression of the nerves that run between the brain and the
nose. If the tumor grows large enough, vision problems may occur due to compression of the optic
nerve.
 Suprasellar: Vision problems due to compression of the optic nerves/chiasm.
 Posterior Fossa: Facial symptoms or loss of hearing due to compression of cranial nerves, unsteady
gait and problems with coordination.
 Intraventricular: May block the flow of cerebrospinal fluid, resulting in obstructive hydrocephalus,
potentially leading to headaches, lightheadedness and changes in mental function.
 Intraorbital: Buildup of pressure in the eyes, leading to a bulging appearance and potential loss of
vision.
 Spinal: Back pain or pain in the limbs caused by compression of the nerves that run into the spinal
cord.

Diagnosis
It can be difficult to diagnose meningiomas for several reasons. Because the majority of meningiomas are
slow-growing tumors and primarily affect adults, symptoms may be so subtle that the patient and/or doctor
may attribute them to the normal signs of aging. Adding to the confusion is that some of the symptoms
associated with meningiomas can also be due to other medical conditions. Misdiagnosis is not uncommon
and, in fact, may take several years to diagnosis correctly.
When a patient presents slowly increasing signs of mental dysfunction, new seizures or persistent
headaches or if there is evidence of pressure inside the skull (e.g. vomiting, swelling of the optic nerve
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head in the back of the eye), the first step should be a thorough neurological evaluation, followed by
radiological studies, if needed.
Sophisticated imaging techniques can help diagnose meningiomas. Diagnostic tools include computed
tomography (CT or CAT scan) and magnetic resonance imaging (MRI). Intraoperative MRI is also used
during surgery to guide tissue biopsies and tumor removal. Magnetic resonance spectroscopy (MRS) may
be used to examine the tumor's chemical profile and determine the nature of the lesions seen on the MRI.
Sometimes, the only way to make a definitive diagnosis of the meningioma is through a biopsy. The
neurosurgeon performs the biopsy to obtain tissue for examination by the neuropathologist to establish the
diagnosis, determine whether the tumor is benign or malignant (and establish a tumor grade) so doctors
can recommend an appropriate clinical management plan.

Treatment Options

Surgery
Meningiomas are primarily benign tumors with defined borders that enables complete surgical removal,
which offers the best chance for a cure. The neurosurgeon opens the skull through a craniotomy to enable
full access to the meningioma. The goal of surgery is to remove the meningioma completely, including the
fibers that attach it to the coverings of the brain and bone. However, complete removal can carry potential
risks that may be significant, especially when the tumor has invaded brain tissue or surrounding veins.
Although the goal of surgery is to remove the tumor, the first priority is to preserve or improve the patient's
neurological functions. With patients for whom total removal of the tumor carries significant risk of morbidity
(any side effect that can cause decreased quality of life), it may be better to leave some of the tumor in
place and observe future growth with regular imaging studies. In such cases, the patient will be observed
over a period of time with regular examinations and MRIs, while for other patients, radiation therapy may
be deemed the best approach. It is common for patients to undergo preoperative embolization of the tumor
to ensure safety during the surgical procedure. The embolization procedure is similar to a cerebral
angiogram except that the surgeon fills the blood vessels in the tumor with a compound to stop blood
supply to the tumor. 

Observation
Observation over a period of time may be the appropriate course of action in patients who meet the
following criteria:
 Patients with few symptoms and little or no swelling in the adjacent brain areas
 Patients with mild or minimal symptoms who have a long history of tumors without much negative effect
on their quality of life
 Older patients with very slow-progressing symptoms
 Patients for whom treatment carries a significant risk
 Patients who choose not to have surgery after being offered alternate treatment options

Radiation Therapy
Radiation therapy uses high-energy X-rays to kill cancer cells and abnormal brain cells, and to shrink
tumors. Radiation therapy may be an option if the tumor cannot be treated effectively through surgery.
 Standard external beam radiotherapy uses a variety of radiation beams to create a conformal coverage
of the tumor, while limiting the dose to surrounding normal structures. The risk of long-term radiation
injury with modern delivery methods is very low. Newer techniques of delivery aside from 3-dimensional
conformal radiotherapy (3DCRT) include intensity-modulated radiotherapy (IMRT).
 employs a specific type of radiation in which protons, a form of radioactivity, are directed specifically to
the tumor. The advantage is that less tissue surrounding the tumor incurs damage.
 Stereotactic radiosurgery (such as Gamma Knife, Novalis and Cyberknife) is a technique that focuses
the radiation with many different beams on the target tissue. This treatment tends to incur less damage
to tissues adjacent to the tumor. Currently, there is no data to suggest one delivery system is superior
to another in terms of clinical outcome. Each has its advantages and disadvantages.

Chemotherapy
Chemotherapy is rarely used to treat meningioma, except in atypical or malignant subtypes that cannot be
adequately treated with surgery and/or radiation therapy.
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Outcome
In adults, the patient's age at the time of diagnosis is one of the most powerful predictors of outcome. In
general, the younger the adult, the better his or her prognosis tends to be. There generally is a better
outcome if the entire tumor is surgically removed; however, this is not always possible due to the location
of the tumor.
Data from the Central Brain Tumor Registry of the United States Statistical Report indicates an overall ten-
year survival rate for non-malignant meningioma of 84%. Individuals with malignant meningiomas have an
overall ten-year survival rate of 62%. Non-malignant meningiomas of the spine conferred a better ten-year
survival (96%) than non-malignant meningiomas of the cerebral meninges (83%). Furthermore, malignant
spinal meningiomas had higher ten-year survival rates (73%) than malignant brain meningiomas (55.7%).

WHO grading of meningiomas

 WHO grades meningiomas on a scale from I to III
 Majority of meningiomas are WHO grade I
 Grades by subtype
o Grade I:
 Meningothelial
 Fibrous (fibroblastic)
 Microcystic
 Transitional
 Psammomatous
 Angiomatous (includes hemangioblastic, angioblastic)
 Secretory subtypes
 Metaplastic
 Lymphoplasmacyte rich
o Grade II:
 Clear cell and chordoid subtypes or atypical by criteria
o Grade III:
 Rhabdoid and papillary subtypes or anaplastic by criteria

 Criteria for atypical meningioma, WHO grade II (5 - 15% of all meningiomas)

o 4 - 19 mitotic figures/10 HPF OR
o Brain invasion OR
o Three of these histologic features:
 Increased cellularity
 Small cells with high N/C ratio
 Large and prominent nucleoli
 Patternless or sheet-like growth
 Foci of "spontaneous" or geographic necrosis

 Criteria for anaplastic meningioma, WHO grade III (1 - 2% of all meningiomas)

o Either 20 or more mitotic figures/10 HPF OR
o Display frank sarcomatous or carcinomatous histology

Histopathology
The pathognomonic histologic feature of a meningioma is spherical formations of meningothelial cells,
called whorls, which eventually mineralize into psammoma bodies (Figure 2). Central chromatin clearing is
also common in tumor nuclei, as are cytoplasmic invaginations into the nuclei, known as intranuclear
cytoplasmic pseudoinclusions. However, these features are often inconspicuous or absent in many
meningiomas. A range of histologic patterns and findings can be seen that often mimic other soft tissue
tumors, as indicated by the numerous variants just among benign grade I tumors: meningothelial, fibrous,
transitional, psammomatous, angiomatous, microcystic, secretorym, lymphoplasmacyte-rich and
metaplastic. The most widely used immunohistochemical marker to identify a meningioma is epithelial
membrane antigen, although more recent studies have clearly shown that somatostatin receptor 2A
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(SST2A) is a superior immunostain target [19]. Approximately 70–80% of meningiomas are positive for
progesterone receptor and, to a much lesser degree, estrogen receptor [20,21], consistent with the
epidemiologic preponderance of meningiomas in females, and strongly suggesting a hormonal component
to tumor growth.

Histologic features of WHO grade I–III meningiomas.

(A) Grade I tumors typically contain numerous whorls of meningothelial cells (black arrow), with varying
stages of maturation into mineralized psammoma bodies (white arrow). (B) Nuclear clearing (black arrows)
and intranuclear cytoplasmic pseudoinclusions (white arrow) are common in grade I tumors, but mitoses
and large nucleoli are not. (C) Invasion into the underlying brain (black arrow) is a feature of many grade II
meningiomas. (D) Four to 19 mitoses per ten high-power fields (black arrow) and prominent nucleoli (white
arrow) are also seen in grade II tumors. (E) Grade III meningiomas usually show increased cellularity and
micronecrotic foci (black arrows) and (F) such tumors have 20 or more mitoses per ten high-power fields
(black arrows). Scale bar in F = 120 μm in (A) and (C), 300 μm in (E) and 30 μm in (B), (D) and (F).

Since the publication of revised WHO 2016 guidelines meningiomas are classified as grade II ‘atypical’
tumors if they have either 4+ mitoses per ten consecutive high-power fields (using a 40× objective) or brain
invasion, defined as meningioma pushing into the underlying cortex without an intervening layer of
connective tissue [22]. In other words, a meningioma that is adherent to underlying brain is not necessarily
grade II, as there must be unequivocal invasion of the tumor into the gray matter. If neither feature is
present, at least three of the following five histologic criteria must be evident to arrive at a grade II
diagnosis: intratumoral micronecrosis not caused by presurgical thrombosis therapy; patternless sheets of
tumor cells; prominent nucleoli (i.e., readily visible with a 10× objective); high cellularity; and tumor cells
with scant cytoplasm relative to nuclear size (small cell changes) [22]. Brain invasion, which has been
shown to be an independent adverse marker of tumor recurrence, is now used as a standalone criterion for
a grade II diagnosis [22]. A Ki67 proliferation index over 4% has also been correlated with increased
recurrence risk [23], but is most commonly used as an adjunct to standard WHO grading, rather than as an
independent indicator of grade.

Schwannoma
Acoustic neuromas (also known as vestibular schwannomas) are benign tumors that arise from Schwann
cells and primarily originate within the vestibular portion of cranial nerve VIII. The tumor forms within the
internal acoustic canal with variable extension into the cerebellopontine angle. Most tumors are unilateral.
Bilateral acoustic neuromas strongly suggest the genetic condition neurofibromatosis type II. Symptoms
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are related to compression of cranial nerves VIII, V, VII, and the cerebellum. The most common symptom
is unilateral sensorineural hearing loss. Diagnosis of acoustic neuroma involves audiometry that
demonstrates ipsilateral sensorineural hearing loss and MRI with contrast to confirm the tumor. For
patients with large tumors or significant hearing loss, the treatment of choice is surgical removal
or radiation therapy. However, observation with follow-upmay be appropriate for patients with smaller
tumors and minimal hearing loss. On average, the prognosis is favorable, as acoustic neuromas are
usually benign, slow-growing tumors with low recurrence rates.

Definition 
 Benign tumors that arise from Schwann cells

Epidemiology 
 Median age: 50 years
 Incidence: 1/100,000 person-years
 Commonly located within the internal acoustic canal and can extend into the cerebellopontine angle
o Most common tumor of the cerebellopontine angle
 Unilateral in 90% of cases
Bilateral acoustic neuromas are strongly associated with neurofibromatosis type II.

Clinical features 
 Early symptoms with insidious onset: caused by pressure on the vestibulocochlear nerve (CN
VIII) as a result of tumor expansion into the internal acoustic canal (internal auditory meatus) 
o Cochlear nerve involvement 
 Unilateral sensorineural hearing loss (most common symptom)
 Tinnitus
o Vestibular nerve involvement 
 Dizziness
 Unsteady gait and disequilibrium
 Late symptoms: caused by pressure of adjacent structures within the cerebellopontine angle
o Trigeminal nerve (CN V) involvement: paresthesia (numbness), hypoesthesia (decreased
sensation), and/or unilateral facial pain
o Facial nerve (CN VII) involvement: peripheral, unilateral facial weakness that can progress
to paralysis 
o Compression of structures in posterior fossa
 Cerebellum: ataxia
 4th ventricle: hydrocephalus

Diagnostics 
 Cranial nerve testing
o Cochlear nerve (CN VIII): sensorineural hearing loss
 Audiometry
 Hearing loss with greater deficit for higher frequencies
 Best initial screening test: > 95% of patients will have some type of hearing
loss.
 Weber test: lateralization to the normal ear
 Rinne test: air conduction > bone conduction in both ears
 Brainstem-evoked audiometry: delay in cochlear nerve conduction time on affected
side finding 
 Can be used as additional screening tool in patients with asymmetric
audiometry findings
 Less commonly used because of the increased sensitivity and availability
of MRI screening 
 Contrast MRI (imaging modality of choice)
o Recommended in patients with abnormal audiometric testing or high clinical suspicion of
acoustic neuroma (cerebellopontine angle syndrome)
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o CT with and without contrast is an alternative for those who cannot undergo MRI. 
o Shows an enhancing lesion by the internal auditory canal, with possible extension into
the cerebellopontine angle.

Treatment 
 For those with large tumors or significant hearing loss, the main treatment options are surgery
or radiation therapy.
 Observation of the tumor can be considered in patients with small tumors or minimal hearing loss,
or if they are of advanced age. These patients should undergo MRI surveillance every 6–12
months.

Prognosis 
 Good prognosis: Neuromas are a WHO grade I brain tumor with a low rate of recurrence.

10. Anaplastic meningioma (WHO grade III)

Anaplastic meningiomas (also known as malignant meningiomas) are uncommon, accounting for only
~1% of all meningiomas 1. Along with rhabdoid meningioma and papillary meningioma are considered
WHO grade III tumors and demonstrate aggressive local growth and high recurrence rate. 
It should be noted that epidemiology, clinical presentation and radiographic features do not reliably
distinguish anaplastic meningiomas from benign meningiomas (WHO grade
I) and atypical meningiomas (WHO grade II), and thus that content is unnecessarily repeated here.
Generally, these tumors grow faster, have more heterogeneous/aggressive imaging appearances, and
have a tendency to recur early. 

Pathology
Anaplastic meningiomas are those with the following histological characteristics 1:
 obvious malignant features similar to those seen in melanoma, carcinoma, or high-grade sarcoma
 20 or more mitosis per ten high-power fields

Radiographic features
Generally, it is not possible to confidently distinguish benign (WHO grade I) and atypical (WHO grade II)
from anaplastic (WHO grade III) meningiomas on general morphology. The most reliable feature in
suggesting a non-grade I tumor is the presence of lower ADC values (reflecting higher cellularity)  2,3.
Importantly presence of vasogenic edema in adjacent brain parenchyma is not a predictor of atypical or
anaplastic histology 3. 
Brain invasion, although by definition denoting at least a grade II tumor, is also surprisingly difficult to
predict on MRI. 

Treatment and prognosis

First line therapy is surgical resection with radiotherapy (external beam or brachytherapy) often added both
for complete and incomplete resections (see Simpson grade). Radiation has been shown to improve local
control and prolongs overall survival 5. 
No effective chemotherapeutic agents have been identified 4. 
The recurrence rate is significantly higher (50-94%) than that seen in grade II meningiomas (29-52%) and
this correlates with reduced survival 5.

11. Tutorial 2 Page 2 and normal histology meningeal cells

The bright field microscopy image of the subarachnoid space is shown in Figure 3, where the arachnoid
and the pia mater are identified. The figure also shows that there is a gap between the pia mater and the
brain which is caused by the injection of the Microfil. The tissue studied under the fluorescence light
microscopy is shown in Figure 4, and here collagen tissues can be clearly seen. From these initial
experiments it was determined that the subarachnoid space collapses easily in the absence of CSF, and
injection of rubber silicon may rupture the trabeculae.
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Light microscopic view of subarachnoid, (a) the arachnoid mater, (b) SAS, (c) the pia mater, and (d) the
brain.

Fig. 15. Meninges are connective tissue layers surrounding the brain, the spinal cord, and the roots of
peripheral nerves. The pia mater (P) is a delicate connective tissue layer attached directly to the white
matter of the spinal cord. The dura mater (D) is a thick connective tissue layer. It is the most superficial of
the three meningeal layers. The arachnoid (arachnoid membrane) is attached to the deep surface of the
dura mater (A). Arachnoid trabeculae (arrows) extend from the arachnoid to the pia mater.
The subarachnoid space (asterisks), between the arachnoid and pia mater, is lined by flat fibrocytes and
contains cerebrospinal fluid. (The subarachnoid space is collapsed due to fluid loss in the above image.)

12. Therapy algorithm for meningioma

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TREATMENT

SURGERY
Surgery is the primary treatment for meningiomas located in an accessible area of the brain or spinal cord,
although some tumors may be inoperable. Another factor that neurosurgeons consider is whether your vital
organs (heart, lungs, kidneys and liver) are strong enough to withstand anesthesia and surgery.
The goals of surgery are to obtain tumor tissue for diagnosis and to remove as much tumor as possible. If
the tumor cannot be removed, a biopsy to obtain a sample of tumor tissue may be performed.
A computer program that combines different MR images taken before surgery may be used to make a
three dimensional, or stereotactic, map of your brain. This map helps the neurosurgeon plan the surgery
to remove as much of the tumor as possible while avoiding parts of the brain that control vital functions.
During the operation, the surgeon may use stereotactic imaging and instrument guiding technologies to
navigate through the brain. Occasionally, surgery is performed within a specialized MRI (intraoperative
MRI), which allows the surgeon to view the tumor during the operation and determine the extent of tumor
that is removed. High powered microscopes may be used to help the surgeon to better see the tumor.
Ultrasonic aspirators are used to break up and suction out parts of the tumor.
In cases where the tumor cannot be removed completely, partial removal can help decrease symptoms.
Radiation may then be used to treat the remaining tumor.

RADIATION
Radiation therapy (external beam) may be used for inoperable tumors, tumors that are not completely
removed in surgery, atypical and malignant tumors, or recurrent tumors. There are different types of
radiation, which use various doses and schedules. Most forms of radiation, however, are aimed at the
tumor and a small area around the tumor.
Conventional external beam radiation is “standard” radiation given five days a week for five or six weeks.
Stereotactic radiation aims converged beams of radiation at the tumor. Intensity modulated radiation
therapy, also called IMRT, conforms radiation beams to the shape of the tumor. Additional information
about these forms of radiation therapy is available from our office.
Stereotactic radiosurgery (SRS) utilizes numerous finely focused beams of radiation to accurately
administer
a single high-dose treatment to the tumor, while minimizing the effects to adjacent normal tissue.
Therefore, despite the name, this is a noninvasive procedure and there is no real “surgery” involved.
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This may be particularly advantageous for patients

that are poor surgical candidates, have tumors in high- risk regions of the brain, or have recurrences that
are no longer amenable to conventional forms of surgical and radiation therapies. The disadvantages are
that if no surgery or biopsy is done, no tissue is obtained for examination under the microscope; the
technique may only inhibit further growth, stabilizing – rather than killing or removing – the tumor, and the
technique is limited to relatively small tumors, usually those that are less than three centimeters in size.
For large tumors, or tumors located close to critical structures, conventional or stereotactic radiotherapy
is often used instead. While stereotactic radiosurgery (SRS) involves the use of a single large dose of
focused radiation, stereotactic radiotherapy, (SRT), involves the administration of smaller doses of focused
radiation over a longer period of time (up to several weeks). This reduces the potential for swelling or injury
to surrounding structures.

OTHER TREATMENTS
Systemic therapy may be indicated for tumors that are not surgically accessible or for patients in whom
further radiation is not possible. Some of these treatments are offered in organized research studies called
clinical trials. Your doctor can determine if you are a candidate for treatment in one of these trials.
Several other treatment approaches have or are being explored:
 Hydroxyurea (used as a radiosensitizing drug in the treatment of other types of tumors)
 Progesterone receptor inhibitors (eg. mifepristone)
 Somatostatin analogs (hormones that prevent the release of growth hormones) (eg. octreotide)
 Targeted molecular agents (eg. everolimus)
 Epidermal growth factor receptor (EGFR) inhibitors (eg. erlotinb)
 Platelet-derived growth factor receptor (PDGFR) inhibitors (eg. imatinib)
 Vascular endothelial growth factors (VEGF) inhibitors (eg. bevacizumab)
 Immunotherapy or the use of biological agents to stimulate the immune system (eg. interferon alfa,
nivolumab)
There are also several drugs used to treat the symptoms of a brain tumor. Steroids are used to decrease
swelling, or edema, around the tumor. Anti-seizure drugs control seizures. Anti-nausea drugs prevent
vomiting and help control nausea. Additional suggestions for managing side effects are offered on the
ABTA website at www.abta.org.

WATCHFUL WAITING
Depending on the location of the tumor, symptoms caused by the tumor and sometimes patient preference,
some meningiomas may be carefully watched. Scans will be recommended during the time of observation,
and it is very important to be sure those scans are done. If your doctor suggests a course of observation,
remember that any new or changed symptoms should be promptly reported to your doctor.

RECURRENCE
Most meningiomas are benign and treatable with surgery. However, brain tumors recur when all of the
tumor
cells cannot be removed with surgery or killed with other treatments. Over time, those cells multiply and
result in tumor regrowth. Your doctor can talk with you about the chances of your tumor recurring. In
general,
at five years following surgery, about 5% of completely resected benign meningiomas, 30% of partially
resected benign meningiomas and 40% of atypical meningiomas have recurred. Although rare, it is also
possible that the meningioma may recur as a more aggressive, or higher grade, tumor.
Depending on your general health and the growth characteristics of the tumor, repeat surgery and possibly
radiation therapy can be considered if the tumor recurs. Focused forms of radiation therapy, such as
stereotactic radiotherapy or radiosurgery, may be repeated or used following a history of conventional
radiation therapy. Treatments offered in clinical trials may also be used for recurrent tumors.

RECOVERY
As with any brain tumor treatment, the length of recovery time varies. The age and general health of the
patient, the location and size of the tumor, and the type of treatment all affect the recovery time. Prior to
your surgery, ask your doctor what side effects you might expect.
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Muscle coordination or speech problems may occur following surgery depending on the location of the
tumor; they are often temporary. During this healing time, many brain tumor patients discover the benefits
of rehabilitative services. The goal of rehabilitative medicine is to restore physical, vocational and
psychological functions. Services may include physical, occupational and/or speech therapy to help reduce
some of the symptoms that may accompany a tumor
or treatment. Cognitive retraining – a memory training method – is used to teach another part of the brain
to take over the tasks of the impaired portion. Visual aids may be required for those with tumors near the
optic nerves. Support services that help patients and their families live with a brain tumor diagnosis are just
as important. Call the ABTA’s CareLine at 800-886-ABTA (2282) for help locating both rehabilitative and
support services in your area. For additional information, access to ABTA’s online support community and
to view webinars, please visit www.abta.org.

PROGNOSIS
People diagnosed with a meningioma often have very specific questions regarding their future. They may
want to know the risks involved in their surgery, the need for follow-up care or additional treatments, if or
how the tumor might affect their life, and what the chances are for their tumor recurring. Although the
medical term “prognosis” is usually associated with malignant tumors, a “predication of outcome” may be
more applicable to a person with a meningioma.
We encourage you to ask your doctor these outcome questions. They can respond to your concerns based
on your individual tumor. Your doctor can also explain your treatment plan, the benefits and risks of the
treatment plan suggested for you, and what you can expect in the future.

13. Ataxia

A lack of coordination of voluntary movements. Common causes include impaired cerebellar function
(cerebellar ataxia), impaired vestibular function, and/or loss of proprioceptive sensation (sensory ataxia).
Ataxias may be classified as either motor (cerebellar) or sensory.

Motor ataxias (also referred to as cerebellar ataxias) are usually caused by disorders of the cerebellum.
The sensory receptors and afferent pathways are intact, but integration of proprioceptive information is
faulty. Involvement of the lateral cerebellum (one of the cerebellar hemispheres) may lead to a motor
ataxia of the ipsilateral limb. Lesions affecting primarily the midline portion of the cerebellum often cause
problems with axial muscle coordination, which is reflected in difficulty maintaining a steady upright
standing or sitting posture.
There are many reports of CNS lesions producing motor ataxia in what intuitively seem unlikely locations.
Supratentorial infarctions, particularly small, deep infarctions, and lacunae of the posterior limb of the
internal capsule have been reported to cause isolated hemiataxia. It is postulated that interruption of either
ascending or descending cerebellar to cortical pathways are the cause of this motor-type ataxia. Small
infarctions or hemorrhages in thalamic nuclei may produce a clinical picture of motor- or cerebellar-like
ataxia with hemisensory loss. These effects are seen contralateral to the lesion. Lesions affecting the
frontal lobe, such as tumors or cystic masses, may cause a motor ataxia of the contralateral extremities
through poorly understood mechanisms. Nontraumatic spinal cord compression may present with gait
ataxia or abnormality.

Sensory ataxias are due to failure of transmission of proprioception or position sense information to the
CNS. Failure may arise from disorders affecting the peripheral nerves, spinal cord, or cerebellar input
tracts. Coordinated motor performance is faulty, even though motor systems and the cerebellum are intact.
Sensory ataxias may be somewhat compensated by visual sensory information. Loss of visual information
leads to the observation that sensory ataxias often worsen in poor lighting conditions.
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ANATOMY OF ATAXIA: CEREBELLAR MODULES

Spinocerebellum
 Involves the limbs and trunk.
 Primarily involves the anterior lobe and vermis.
 The spinocerebellum receives its name from its major input fibers: the spinocerebellar tracts and, as
we can imagine, plays a major role in postural stability.

Pontocerebellum
 Involves the arms.
 Primarily derives from the posterior lobe.
 It is geared towards fine motor movements, which are typically goal-oriented (it primarily acts through
the corticopontocerebellar pathway).

Vestibulocerebellum
 Involves the face.
 Primarily derives from the flocculonodular lobe.
 It is important for equilibrium and eye movements.

ATAXIA IN RELATION TO ALCOHOL TOXICITY

Acute Alcohol Toxicity
Acute alcohol intoxication causes toxicity to the entire cerebellum:
 Spinocerebellar toxicity causes truncal ataxia.
 Pontocerebellar toxicity causes incoordination.
 Vestibulocerebellar toxicity causes nystagmus.

Chronic Alcohol Toxicity

Chronic alcohol toxicity causes anterior superior cerebellar vermian degeneration, which leads to truncal
ataxia. This is easily missed, if we fail to ask our patients to stand during the exam.

GENETIC ATAXIA SYNDROMES

Autosomal Recessive:
 Friedreich's ataxia (FA): notably manifests with arreflexia (from the neuropathic component) but also
pathologic reflexes (eg, Babinski sign).
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Remember that this mixed pattern can also present in subacute combined degeneration from Vitamin
B12 deficiency: ataxia (from dorsal column degeneration), pathologic reflexes (from the myelopathy),
arreflexia (from neuropathy).
 Ataxia with Vitamin E Deficiency: far more rare than FA but presents similarly, and, importantly,
vitamin E repletion can halt the progression of the disease.

Autosomal dominant:
 Spinocerebellar ataxias (SCAs): generally we divide these into the pure cerebellar disorders and the
ataxias with extra-cerebellar signs, as well (see below for details).
 Episodic ataxias: notably causes ataxia attacks. There are currently 7 types of episodic ataxia, but,
importantly, EA1 and EA2 respond to pharmacological treatment (Both respond to acetazolamide,
EA2 also responds to dalfampridine (4-aminopyridine), which we use in multiple sclerosis).

X-linked disorders:
 Mitochondrial disorders (eg, MERRF)
 Fragile X-tremor/ataxia
 X-linked adrenoleukodystrophy

Sporadic:
 As an example, multiple systems atrophy (MSA) - an atypical parkinsonian disorder that involves
autonomic dysfunction + cerebellar disease or parkinsonism.

SPINOCEREBELLAR ATAXIAS
There are greater than 30 SCAs, so we'll limit our review to the most common: SCAs 1, 2, 3, 6, 7, and
DRPLA, which account for 50 – 75% of the cases, worldwide, and all of which are expanded exon-coding
CAG repeat disorders. The SCAs comprise a variety of autosomal dominant mutations in addition to the
expanded exon-coding CAG repeat mutations (eg, non-coding region expansion mutations and other
conventional mutations).
We'll categorize these into their Harding Classification of Autosomal Dominant Cerebellar Ataxias (ADCA I
– III) to help group them by their clinical phenotypes.

ADCA 1
ADCA 1 are ataxias that also share any of the following features: ophthalmoplegia with or without optic
atrophy, extrapyramidal features, dementia, extrapyramidal features, and/or amyotrophy.
 SCA1 manifests with ataxia along with, most notably, pyramidal tract signs and slowing of saccades
to the point of ophthalmoplegia.
 SCA2 has a similar clinical phenotype to SCA1 but with slow saccades early-on.
 SCA3 (Machado-Joseph disease) is the most common SCA, worldwide, and, in addition to ataxia,
notably, has features of levodopa-responsive parkinsonism (making it key part of the atypical
parkinsonism differential), brainstem and ophthalmologic signs, amyotrophy, and polyneuropathy.
 DRPLA (Dentatorubral-Pallidolusian Atrophy), which, as a simplification, we can think of as Japanese
Huntington's disease with atrophy of the brainstem and cerebellum, since most cases are from Japan
and because of the overlap in symptomatology, and because the atrophy in HD it is the caudate
whereas in DRPLA it is the brainstem and cerebellum. However, there are notable differences in the
disorders that are beyond our scope, here.

ADCA 2
ADCA 2 is most easily thought of as ADCA 1 plus pigmentary retinal degeneration
 SCA7 most notably presents with severe visual loss from maculopathy, along with numerous other
signs similar to SCAs 1 – 3.

ADCA 3
ADCA 3 is a pure cerebellar syndrome (with later age of onset, typically)
 SC6 presents as a benign, slowly progressive ataxia, typically in the 50s to 60s; accordingly the
pathology is confined to the cerebellum.
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Ataxia, defined as impaired coordination of voluntary muscle movement, is a physical finding, not a

disease, and the underlying etiology needs to be investigated. 
 Ataxia can be the patient’s chief complaint or a component among other presenting symptoms.  
 Ataxia is usually caused by cerebellar dysfunction or impaired vestibular or proprioceptive afferent
input to the cerebellum. 
 Ataxia can have an insidious onset with a chronic and slowly progressive clinical course (eg,
spinocerebellar ataxias of genetic origin) or have an acute onset, especially those ataxias
resulting from cerebellar infarction, hemorrhage, or infection, which can have a rapid progression
with catastrophic effects. [1]
 Ataxia is manifested by a wide-based unsteady gait, errors of extremity trajectory or placement,
errors in motor sequence or rhythm and/or by dysarthria. Tone is usually decreased and
stretch reflexes may be “pendular.” Nystagmus, skew deviation, disconjugate saccades, and
altered ocular pursuit can be present. Truncal instability and tremor of the body or head may
occur, especially with cerebellar midline disorders.

Clinically Relevant Anatomy

Ataxia is usually caused by cerebellar dysfunction or impaired vestibular or proprioceptive afferent
input to the cerebellum. 
Any of the following can be implicated in pathology. Cerebellum, spinal cord, brain
stem, vestibularnuclei, basal ganglia, thalamic nuclei, cerebral white matter, cortex(especially frontal),
and peripheral sensory nerves.

Classification of Disorders Causing Ataxia

Ataxia is a manifestation of a variety of disease processes, and an underlying aetiology needs to be
investigated. 
 Pure ataxia is rare in acquired ataxia disorders, and associated symptoms and signs almost
always exist to suggest an underlying cause. 
 The spectrum of hereditary degenerative ataxias is expanding
 Attention should be addressed to those treatable and reversible etiologies, especially potentially
life-threatening causes.
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Mass Lesions
eg medulloblastoma, cystic astrocytoma, hemangioblastomas, and metastatic processes.

Vascular Disorder
Eg., Hemorrhage or infarction of cerebellum. A study found that the ataxia severity is associated with
the severity of the inferior cerebellar peduncle (ICP) injury in patients with cerebral infarct, suggesting
that evaluation of the ICP using diffusion tensor tractography (DTT)  as a useful tool for patients with
ataxia after cerebral infarct.

Infectious and Post-infectious Processes

Eg., Bacterial cerebellitis can occur with meningitis, penetrating trauma or extension of an epidural
process, most commonly from temporal bone; Prion-associated encephalopathies include sporadic
Creutzfeldt-Jakob disease (sCJD); Acute cerebellitis (acute cerebellar ataxia) is a para-infectious
disorder; Fisher syndrome, a Guillain-Barré variant, involves the peripheral and central nervous
system. 

Trauma
Gait instability may persist following cerebellar, vestibule, brain stem, or frontal lobe injury or with
interruption of the frontopontocerebellar tract. In acute trauma, or progressive post-traumatic ataxia,
an expanding cyst or extra-axial hematoma should be considered.

Demyelinating Disorders
Ataxia is common in early and late multiple sclerosis. 

Congenital Disorders
eg. Machado-Joseph Disease (Spinocerebellar Ataxia Type 3), Dandy Walker Syndrome; Joubert
syndrome; Ataxia can also occur with perinatal cerebral infarction and with congenital CNS infection.

Hereditary and Idiopathic Degenerative Processes

Hereditary ataxias are classified by the causative gene (when known) and their pattern of inheritance.
eg spinocerebellar ataxias; Huntington Disease; Friedreich's ataxia; Fragile X tremor/ataxia
syndrome; Multiple system atrophy(MSA) is a sporadic disorder that initially manifests after age 50 by
ataxia (MSAc); Parkinsonism; Mitochondrial disorders are also associated with progressive ataxia.

Paroxysmal Disorders Associated with Ataxia

Intermittent ataxia has been associated with epilepsy, migraine, and high systemic fever in otherwise
healthy children. Intermittent ataxia can also be associated with abnormalities in membrane calcium
or potassium channel function, or with altered synaptic glutamate transport.

Spinal Cord and Peripheral Nerve-Related Ataxia

Spinal cord and/or nerve root disorders can produce ataxia. 

Nutritional Deficiency, Toxins and Drugs

Solvent abuse or toxic exposure to solvents, methyl-mercury poisoning(Minamata disease),
metronidazole (Flagyl)-induced cerebellar toxicity, central pontine myelinolysis (osmotic demyelination
syndrome), leukoencephalopathy relating to the inhalation of heroin vapors, vitamin E
deficiency, Alcoholism, Wernicke encephalopathy, and reversible posterior leukoencephalopathy can
each be associated with the acute or chronic presentation of ataxia. [2]

Clinical Presentation
Ataxia is usually caused by cerebellar dysfunction or impaired vestibular or proprioceptive afferent
input to the cerebellum. 
 Ataxia can have an insidious onset with a chronic and slowly progressive clinical course
(eg, spinocerebellar ataxias of genetic origin) 
 Ataxia can have an acute onset, especially those ataxias resulting from cerebellar infarction,
haemorrhage, or infection, which can have a rapid progression with catastrophic effects.  
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 Ataxia can also have a subacute onset, as from infectious or immunologic disorders, which
may have a limited window of therapeutic opportunities [1]
 Symptoms and signs are often related to the location of the lesions in the cerebellum.  
 Lateralized cerebellar lesions cause ipsilateral symptoms and signs, whereas diffuse
cerebellar lesions give rise to more generalized symmetric symptoms. Lesions in the cerebellar
hemisphere produce limb (appendicular) ataxia. 
 Lesions of the vermis cause truncal and gait ataxia with limbs relatively spared.  
 Vestibulocerebellar lesions cause disequilibrium, vertigo, and gait ataxia.  
 Acute pathology in the cerebellum may initially produce severe abnormalities; this may recover
remarkably with time and can become asymptomatic even when imaging shows persistent
dramatic structural changes in the cerebellum. 
 Chronic progressive ataxia is not only due to neurodegenerative or inherited cerebellar
diseases but also neoplasms and chronic infections.

Common Symptoms of Ataxia are:

 Lack of coordination
 Slurred speech
 Trouble eating and swallowing
 Deterioration of fine motor skills
 Difficulty walking
 Gait abnormalities
 Eye movement abnormalities
 Tremors
 Heart problems

Terms Describing Ataxia

Physiotherapists should be familiar with the specific ataxia terms and use them appropriately in
documentation and communication with colleagues. It is important to understand the nomenclature
because it often implies a certain ataxic disorder.
 Stance. An impaired stance in the absence of motor weakness or gross involuntary
movements is suggestive of cerebellar ataxia or sensory ataxia.
 Gait ataxia. Gait ataxia results from incoordination of the lower extremities due to cerebellar
pathology or loss of proprioceptive input. Patients often feel insecure and have to hold onto the
wall or furniture and walk with feet apart. An increased gait disturbance when visual cues are
removed (walking with eyes closed or in the dark) suggests a sensory or vestibular component
to the ataxia. With cerebellar causes, the gait ataxia remains the same regardless of visual
cues.
 Sensory ataxia. Sensory ataxia is mainly reflected by gait disturbance. Subjects with sensory
ataxia will have a positive Romberg sign. Subjects may walk with a high-stepping gait (due to
associated motor weakness) or feet-slapping gait (to assist with sound-induced sensory
feedback). 
 Truncal ataxia. Patients may present with truncal instability in the form of oscillation of the
body while sitting (worse with arms stretched out in front) or standing (titubation).
 Limb ataxia. Limb ataxia is often used to describe ataxia of the upper limbs resulting from
incoordination and tremor and can be better described by functional impairment, such as
clumsiness with writing,buttoning clothes, or picking up small objects. The patient has to slow
down the movement to be accurate in reaching things. Limb ataxia can be lateralized with
ipsilateral cerebellar lesions.
 Dysdiadochokinesia/dysrhythmokinesis is tested by rapidly alternating hand movements or
tapping the index finger on the thumb crease. Impairment can be seen with irregularity of the
rhythm and amplitude.
 Intention tremor. Intention tremor results from instability of the proximal portion of the limb
and is manifested by increasing amplitude of oscillation at the end of a voluntary movement. It
is often tested by finger-to-nose and heel-to-shin maneuvers. 
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 Dysmetria. The patient misses the targeted object either due to overshoot (hypermetria) or
undershoot (hypometria). Dysmetria is often tested by a finger-chasing test and can be
quantified by the distance (cm) that is missed. 

 Dysarthria/scanning speech. Often described by the patient or relatives as slurred speech.

The patient’s speech is irregular and slow with unnecessary hesitation. Words are often broken
into separate syllables
 Nystagmus. Often occurs in cerebellar disease. Lateral gaze-evoked nystagmus is seen by
slow drift toward midline followed by a fast phase of saccades to the eccentric position. Upbeat
and downbeat nystagmus are defined by the rapid phase in the up or down direction.  
 Saccades. Saccade speed is typically normal in cerebellar disease but often an overshoot or
undershoot (ocular dysmetria) is present, and is often followed by a corrective saccade in the
appropriate direction.

Weekly Objectives

1. Describe the neuroanatomy of the brainstem including major tracts and 12 cranial nerves which
arise from brain stem, and cerebellum

CRANIAL NERVE 1 : Olfactory  Special Sensory

 Keluar lewat: Cribiform plate of ethmoid bone
 Pathway: superior part nasal cavity ada bipolar olfactory cell  mitral and tufted cell
(olfactory bulb)  Olfactory tract  lateral stria > insulae > amygdale, semilunar gyrus,
ambient gyrus (prepyriformis area) > primary olfactory area (broadmann area 28) 
medial striae  subcallosal area (dibawah genu corpus callosum) > opposite
hemisphere n limbic system > olfactory area (broadmann area 28)  medial forebrain
bundle > hypothalamus > brainstem > salivatory nuclei, vagus nerve nuclei (bikin kita
ngiler kalo nyium bau makanan enak)

Lesions
 Peripheral damage (fila olfactoria) karena rhinitis, trauma  anosmia, hyposmia
 Central damage (olfactory bulb / tract)  anosmia, hyposmia
 Temporal lobe dysfunction  Kakosmia, hyperosmia

CRANIAL NERVE 2 : Optic  Special Sensory

 Keluar lewat: Optic canal
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 Pathway: Retina (photoreceptors, bipolar neuron, ganglion cell) > optic nerve > setengah
dari fiber opticus decussate di optic chiasm > optic tract > superior colliculi > nuclei in
pretectal area > lateral geniculate > optic radiation > visual cortex (medial occipital lobe
broadmann area 17)

Lesions:
 Optic nerve: karena papiledema (kenaikan ICP), vasculitis (temporal arteritis), retrobulbar lesion
(multiple sclerosis)
 Optic chiasm: karena pituit tumor, craniopharyngiona, meningioma

CRANIAL NERVE 3 : Oculomotor  Motor

 Lokasi nukleus: Midbrain (se level sama superior colliculi)
 Keluar lewat: Superior oblique fissure

Lateral nuclear midbrain : superior inferior and medial rectus, inferior oblique, levator palpebrae

Superior branches : Superior rectus (lihat ke atas), levator palpebrae (menaikkan kelopak
mata)

Inferior branches : medial rectus (lihat ke hidung), inferior rectus (lihat ke bawah), inferior oblique

Medial parasympathetic nucleus (edinger-westphal nucleus) midbrain  inferior branches  intraocular

muscle (sphincter papillae muscle and ciliary muscle) = untuk mengecilkan pupil
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Reflex CN 2 & 3:
Impuls yang diterima dari retina itu akan akan terbagi 2 di chiasma opticus.
Jadi, saat mata kiri diberi cahaya, impuls akan ditangkap oleh photoreceptor di retina dan
diteruskan lewat optic nerve, di chiasma opticus fiber yg menerima impuls tersebut akan terbagi
2, satu memberi impuls ke ipsilateral (kiri), satu ke kontralateral (kanan). Selanjutnya kedua
impuls tersebut akan diteruskan ke edinger-westphal nucleus di midbrain, hal ini akan membuat
cilliary muscle berkontraksi = pupil mengecil direct dan indirect.

CRANIAL NERVE 4 : Trochlear  Motor

 Lokasi nucleus: midbrain (selevel dengan inferior colliculi)
 Keluar lewat: Superior orbital fissure
Cranial nerve paling kecil dan cranial nerve satu-satunya yang keluar dari
belakang brainstem baru ke depan.
 Fungsi: Superior oblique muscle (mata lihat ke bawah)

CRANIAL NERVE 6 : Abduncens  Motor

 Lokasi nucleus: Pons
 Keluar lewat: Superior orbital fissure
 Fungsi: Lateral rectus muscle (lihat ke lateral)
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Lesions:
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*trochlear: biasa keluhannya susah turun tangga

CRANIAL NERVE 5 : Trigerminal  Sensory and Motor

Lokasi nucleus: Pons
 Principal sensory nucleus (touch and discrimination)
 Spinal nucleus (pain and temperature)
 Mesencephali nucleus (proprioception)

Keluar lewat: Superior orbital fissure (V1 = Ophthalmic), Foramen rotundum (V2 =
Maxillary), Foramen ovale (V3 = Mandibular)

Pathway:
 Sensory:
Pain  spinal nucleus  thalamus  post central gyrus (ipsilateral)
 Motor:
Pre central gyrus  motor nuclei  masseter, temporalis, pterygoid, anterior belly digastrics
muscle, veli palatine, tensor tympani, mylohyoid muscle (ipsilateral & sedikit impuls ke
contralateral : oleh karena itu tidak langsung kelihatan weaknessnya jika ada defek, tapi bisa
dirasain perbedaan kekuatan kontraksi antara kiri dan kanan)

Lesions:
 Common cause = vascular, MS, tumor, cerebellopontine lesion, herpes zospter
ophthalmicus.
 Peripheral Lesion of motor:
o Flaccid weakness of muscles mastication
o Sensory deficit di area persyarafan trigeminal
o Saat buka mulut  jaw deviate to side of lesion
o Jaw jerk reflex  absent
o Corneal reflex  ipsilateral and contralateral absent

CRANIAL NERVE 7 : Facial  Sensory and Motor and Special Sensory

Lokasi nucleus: Pontomedullary junction
 Main motor nuclei (Caudal pons) : motor cortex  main motor nuclei 7  otot-otot
upper face terima dari hemisphere kanan kiri, otot-otot lower face dari contralateral
hemisphere
 Superior salivatory nuclei (caudal pons) :  pterygopalatine ganglion  lacrimal
gland  submandibular ganglion  salivary gland
 Gustatory nucleus :  geniculate ganglion  2/3 anterior taste bud

Keluar dari : internal auditory meatus, stylomastoid foramen

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Lesions:
 Central : stengah muka bawah kontralateral paralysis  karena stroke
 Peripheral : stengah muka atas dan bawah ipsilateral paralisis  idiopathic,
herpes, stroke brainstem
o Bell’s eye phenomenon: kornea naik ke atas saat pasien mencoba menutup
kelopak mata
o Corneal reflex: ipsilateral absent

CRANIAL NERVE 8 : Vestibulocochlear  Special Sensory

Lokasi nucleus: Pontomedullary junction
 Vestibular nerve : sensory dari kanal semisirkularis ; detect gerakan berputar sensory dari
utricle dan sakulus : detect gravitasi dan gerakan lurus.
Sensory dari kanal semisirkularis, utricle dan sakulus akan disampai kan lewat vestibular
nerve ke vestibular nuclei dan akan berakhir pada floculonodular lobe di cerebellum (untuk
mengatur keseimbangan).
 Cochlear nerve : Menerima impuls dari organ corti, spiral ganglion untuk proses
mendengar.
Untuk proses mendengar : cranial nerve 8  ventral posterior nucleus  parietal cortex

Keluar dari: Internal acoustic meatus

Lesions:
 Ipsilateral deafness
 Tidak seimbang – Jatuh ke arah lesi

CRANIAL NERVE 9 : Glossopharyngeal  Sensory and Motor and Special Sensory

 Lokasi nucleus: Medula oblongata
 Keluar dari: Jugular foramen pars anterior
 Lesions: ipsilateral loss of the gag reflex

CRANIAL NERVE 10 : Vagus  Sensory and Motor

 Lokasi nucleus : Medula oblongata
 Nucleus ambiguous
o Rostral portion  glossopharyngeal nerve  stylopharyngeus muscle
o Middle portion  vagus nerve muscle of the larynx and pharynx
o Caudal portion  intrinsic laryngeal muscle
 Dorsal motor nucleus  viscera of the thorax and abdomen
Keluar dari : Jugular foramen pars anterior
 Sensory fibers
o GVA fibers  larynx, pharynx, trachea, esophagus, baroreceptors in the aortic arch, and the
viscera of the abdomen and thorax
o SVA fibers  taste buds around the epiglottis
 GSA fibers  posterior part of the external auditory meatus and skin behind the ear

Lesions:
 UNILATERAL:
o bilateral loss of the gag reflex
o Palate weakness: nasal regurgitation food
o Unilateral vocal cord weakness: hoarseness, hypophonia
 BILATERAL:
o paralysis of pharynx n larynx : bisa meninggal karena asfiksia

CRANIAL NERVE 11 : Accessorius  Motor

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Lokasi nucleus: Medula oblongata

 Nucleus ambiguus  Cranial root fibers  intrinsic laryngeal muscles through the
recurrent laryngeal
 Spinal accessory nucleus  Spinal root fibers  sternocleidomastoid muscle and
trapezius muscle

Keluar dari: Jugular foramen pars anterior

Lesions:
 Tidak bisa menoleh ke samping, tidak bisa mengangkat bahu
 Winging scapula, Sulit menelan dan berbicara

CRANIAL NERVE 12 : Hypoglossal  Motor

Lokasi nucleus: Medula oblongata
 Hypoglossal nucleus  genioglossus, hypoglossus, and styloglossus muscles.

Keluar dari: Hypoglossal canal

Lesions:
 LMN: unilateran tongue weakness + fasciculation + atrophy + lidah deviasi
ipsilateral dgn lesi saat diminta untuk mengeluarkan lidah
 UMN: unilateran tongue weakness + lidah deviasi kontralateral dgn lesi saat diminta
untuk mengeluarkan lidah

2. Describe the location of nuclei of cranial nerves on brainstem and function of each 12 cranial
nerves
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Cranial Nucleus Function of Nucleus Location

Nerves

Olfactory Anterior Olfactory

Nucleus

Opticus Lateral geniculate The LGN receives information Relay center in the
nucleus directly from the thalamus for the visual
ascending retinal ganglion function
cells via the optic tract and
from the reticular activating
system. Neurons of the LGN
send their axons through
the optic radiation, a direct
pathway to the primary visual
cortex. In addition, the LGN
receives many strong
feedback connections from
the primary visual cortex.
Oculomotor Oculomotor Nucleus Supplies M. Medial rectus, Most lateral of the
M. Superior rectus, M. third nerve nuclei
Inferior rectus, M. inferior
oblique, M. levator
palpebrae

Trochlear Trochlear nuclei Supply GSE fibers to the Near the midline in
superior oblique muscle the anterior part of
the central gray
matter of the lower
midbrain
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Trigeminal Motor (masticatory) Supplies muscle of Lateral pontine

nucleus mastication, tensor tympani, tegmentum just
mylohyoid, anterior belly of medial to main
the digastric muscle, tensor sensory nucleus of
veli palatini the trigeminal

Main sensory Aff : Convey tactile and Lateral to the motor

nucleus pressure sensation from the nucleus
face

Spinal trigeminal Aff : carry input concerning Extending from the

nucleus pain and temperature midpons to the
sensation from the face cervical cord

Mesencephalic Aff : carry proprioceptive Along the lateral

nucleus (this is the input from joints, muscle of border of the central
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only nucleus that mastication, extraocular gray in the upper

receives muscle, teeth, periodontium pons and midbrain
proprioceptive inputs Eff : Supply the extraocular
from musle spindles) muscle

Ophthalmic Purely sensory

division

Maxillary Purely sensory

division

Mandibular Motor and sensory

division

Abducens Abducens nucleus Supplies GSE fibers to the Located in the lower
lateral rectus muscle pons, ventral to the
floor of the fourth
ventricle near the
midline

Facial Main motor nucleus Aff : concerned with the Lateral reticular
upper face receive formation of the
corticobulbar fibers from caudal pons, just
both hemispheres above the superior
Eff : motor fibers to the olive
muscles of the facial
expression include :
Platysma
Stapedius
Orbicularis oculi
Orbicularis oris
Occipitalis
Auricular
Frontalis
Zygomaticus
Buccinator
Stylohyoid
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Superior salivatory Pterygopalatine ganglion Posterolateral to the

nucleus Supply the lacrimal gland motor nucleus of CN
overlying the eye as well as VII
the palatine and nasal
glands of the mouth and
nose
Submandibular ganglion
Secretory efferents to the
submandibular and
sublingual salivary glands

Gustatory nucleus

Trigeminal main Carries some cutaneous

sensory nucleus sensation from the back of
the ear and the external
auditory meatus

Vestibuloco
chlear

Vestibular Carries sensory input from

nerve the cristae ampullaris of the
semicircular canals and the
maculae of the utricle and
saccule

Cochlear Ventral cochlear Carries afferents for the

nerve nucleus and dorsal special sense of hearing
cochlear nucleus

Glossophar SVE fibers Supply stylopharyngeus Arise from the rostral

yngeal muscle nucleus ambiguus

GVA fibers Supply the baroreceptors in The fibers terminate

the carotid sinus on cells in the caudal
part of the nucleus
solitarius
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SVA fibers Carrying taste sensation Terminate in the

from the posterior one-third rostral portion of the
of the tongue travel to the nucleus solitarius
glossopharyngeal nerve

GSA fibers Supplies: Terminate in the

The skin behind the ear caudal part of the
The posterior one-third of spinal trigeminal
the tongue, eustachian tube nucleus
and posterior part of the
upper pharynx

Vagus Main motor nucleus Rostral portion Located in the

(nucleus ambiguus) Sends motor fibers through anterior portion of
the glossopharyngeal nerve the reticular
to supply the formation and
stylopharyngeus muscle extends throughout
Middle portion the medulla
Sends motor fibers through
the vagus nerve to supply
the muscle of the larynx and
pharynx
Caudal portion
Send motors fibers in the
cranial part of the spinal CN
XI that later join the vagus
nerve and supply intrinsic
laryngeal muscle

Dorsal motor Distributed widely to Located anterior to

nucleus postganglionic neurons the floor of the fourth
supplying the viscera of the ventricle and ventral
thorax and abdomen to the sulcus limitans

Sensory fibers GVA fibers

Supply the larynx, pharynx,
trachea, esophagus,
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baroreceptors in the aortic

arch, and the viscera of the
abdomen and thorax
SVA fibers
Supply taste buds around
the epiglottis
GSA fibers
Supply the posterior part of
the external auditory meatus
and the skin behind the ear

Accessory

Cranial root Join the vagus nerve, and Originate from the
fibers finally reach the intrinsic caudal nucleus
laryngeal muscles through ambiguus
the recurrent laryngeal
nerve

Spinal root Supply the Originate from cells

fibers sternocleidomastoid muscle in the spinal
and trapezius muscle accessory nucleus

Hypoglossal Hypoglossal nucleus Supplies GSE fibers to the Located near the
genioglossus, hypoglossus, midline below the
and styloglossus muscles. floor of the fourth
ventricle in the
caudal medulla.

3. Describe the correlation of the clinical findings with specific lesions in the brain stem

No Lesion Information

Medulla
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A Medial Medullary Syndrome (occlusion of the vertebral artery, anterior spinal

artery or one of their branches)

Corticospinal tract lesions Produce contralateral hemiparesis of the arm,

trunk, and leg (UMN lesions)

Medial lemniscus lesions Produce a contralateral deficit of

proprioceptive and tactile sensation
These lesions involve the body but spare the
face

Lesions of the hypoglossal nerve Ipsilateral paralysis of half the tongue

that progresses to muscle atrophy (LMN
lesions)

B Lateral Medullary Syndrome (occlusion of the posterior inferior cerebellar artery)

Spinothalamic tract lesions Produce a pain and temperature sensation

deficit to the contralateral body half

Lesions of the vestibular nuclei and Produce nystagmus, diplopia, vertigo,

pathways nausea, and vomiting

Lesions of the glossopharyngeal Produce ipsilateral dysphagia, horseness, and

and vagus nerves diminished or absent gag reflex

Lesions of descending Produce an ipsilateral Horner syndrome

sympathetic fibers (miosis, pseudoptosis, anhidrosis)

Lesions of the spinal tract and Produce an ipsilateral sensory deficit of half
nucleus of the CN V the face
Pain or parasthesia may oocur on the
ipsilateral half of the face as well as loss of
cerneal reflex

C Unilateral Medullary Syndrome (due to occlusion of the vertebral artey and

produce signs and symptoms of both the medial and lateral medullary syndrome)

Pons

A Lesions of the basal pons

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Corticospinal tract lesions Produce a contralateral hemiparesis of the

arm and leg

Lesions of the abducens nerve Produce an internal strabismus of the

ipsilateral eye

Lesions of the facial nerve Produce an ipsilateral lower motor neuron

lesion that involves the muscle of facial
expression
Facial nerve lesions produce Bell palsy,
and the facial muscle are paralyzed

B Lesions of the medial pons (occlusion of a paramedian branch of the basilar artery)

Corticospinal tract lesions Produce a contralateral hemiparesis of the

arm and leg

Corticobulbar tract lesions Produce a contralateral hemiparesis of the

muscles of facial expression that is more
severe in the lower face

Medial lemniscus lesions Produce a contraleral deficit of tactile and

proprioceptive sensation that involves half of
the body

Lesions of the abducens nucleus Produce lateral gaze paralysis in which both
eys are forcefully directed to the side
contralateral to the lesion

C Lesions of the dorsolateral pons (occlusion of the anterior inferior cerebellar artery
or superior cerebellar artery)

Spinothalamic tract lesions Produce a deficit of pain and temperature

sensation involving the contralateral body

Lesions of the vestibular nuclei and Produce nystagmus, vertigo, nausea,

pathways and vomiting
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Lesions of the cochlear nucleus or Produce unilateral timnitus and deafness
auditory nerve

Lesions of descending Produce an ipsilateral Horner syndrome

sympathetic fibers

Lesions of the spinal tract and Produce impaired ipsilateral facial sensation
nucleus of CN V

Lesions of the facial nucleus Produce ipsilateral facial paralysis, loss of

taste from the anterior two-third of the
tongue, loss of lacrimatation and salvation,
and loss of the corneal reflex

D Pontcerebellar angle syndrome (due to an acoustic neuroma of CN VIII.

This tumor originates from Schwann cells)

Vestibulocochlear nerve lesions Produce timnitus, hearing loss, unsteadiness,

and loss of balance, vertigo, and loss of
normal vestibular reflexes

Trigeminal nerve lesions Produce facial pain, ipsilateral sensory

deficit of half the face, and loss of the
corneal reflex ipsilaterally

Facial nerve lesions Produce ipsilateral facial weakness (usually

late)
Lesions of the inferior and middle Cause failure to produce well-coordinated
cerebellar peduncles voluntary movements predominantly in the
ipsilateral extrimities

E Parimaud syndrome (usually occurs as a result of a pineal tumor. The most

common sign is paralysis of upward gaze, but an impaired downward gaze,
papillary abnormalities (slightly dilated pupil), and signs of elevated ICP)

4. Explain the anatomy and physiology of the vestibular component of cranial nerve VIII, with
emphasis on the role of the vestibular system in eye movement and equilibrium

Canalis semisirkularis ada 3 = superior, horizontal, posterior  untuk jaga keseimbangan saat
berputar utrikle dan sakulus  untuk menjaga keseimbangan saat gerakan lurus
Endolymph = cairan seperti CSF yang membuat bend nya sel-sel rambut (kinosiliom dan stereosilia)

Jika stereosilia bengkok ke arah kinosilium, maka ion channel akan terbuka dan terjadi
depolarisasi. Di bawah ini adalah pathway saat sudah terjadi depolarisasi :
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Cranial nerve 8
 vestibular nuclei superior dan lateral  flocculonodular lobe (Cerebellum)
 vestibular nuclei lateral  Medial longitudinal fasculi  CN 3,4,6
 lateral vestibulospinal tract  jaga posture tubuh
 medial vestibulospinal tract  jaga posture cervical n thoracic

Vestibuloocular Reflex:
contoh: saat seseorang berputar ke arah kanan,

Telinga kanan: endolymph akan bergerak ke arah kiri  menyebabkan stereosilia bend ke arah
kinosilia dan terjadi depolarisasi  impuls di sampaikan lewat nerve vestibularis menuju nucleus
vestibularis  medial longitudinal fasciculus  contralateral nucleus cranial nerve 6 (kiri) 
kontraksi lateral rectus muscle dari mata kiri. Impuls yang sampai di nucleus CN6 juga di
sampaikan ke contralateral oculomotor nuclei (kanan)  kontraksi medial rectus muscle kanan

Telinga kiri: endolymph akan bergerak ke arah kanan  menyebabkan kinosilia bend ke arah
stereosilia dan terjadi hiperpolarisasi  impuls di sampaikan lewat nerve vestibularis menuju
nucleus vestibularis  medial longitudinal fasciculus  contralateral nucleus cranial nerve 6
(kanan)  relaksasi lateral rectus muscle dari mata kanan. Impuls yang sampai di nucleus CN6
juga di sampaikan ke contralateral oculomotor nuclei (kiri)  relaksasi medial rectus muscle kiri

*medial longitudinal fasciculus yang menghubungkan vestibular nuclei dengan nuclei

3,4,6 (-) lesi disini = doll’s eye phenomenon
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Vestibulo-ocular reflex and nystagmus

- Reflex occurs in response to head movement by the vestibular apparatus; results in eye movement in
the opposite direction of the head (to stabilize position of the eye in the line of sight during head
movement.
- Semicircular canals within the vestibular apparatus respond to rotation and angular
acceleration/deceleration of the head
- Contains hair cells (receptors) that create action potential when stimulated
- Afferent pathway: sensory signals generated by hair cells → action potential travels along nerves →
vestibular branch of the vestibulocochlear nerve (CN VIII) → vestibular nuclei in pons
- Efferent pathway:
 From the right vestibular nucleus, nerves cross over to contralateral (left) abducens nucleus →
lateral rectus muscle stimulated via abducens nerve (CN VI) → left lateral rectus muscle contracts
→ left eye moves to left
 Other fibers from left abducens act as interneurons → travel to right oculomotor nucleus → left
lateral, right medius rectus muscles move eye to the left
 Eyes move all the way to the left → creates physiological form of nystagmus (involuntary back-and-
forth eye movement) where eyes move slowly to the left, then rapidly to the right.

5. Understand the pathophysiology of vertigo and disequilibrium

Vertigo adalah sensasi atau perasaan yang mempengaruhi orientasi ruang. Vertigo
dideskripsikan sebagai sensasi berputar.

Vertigo diklasifikasikan menjadi dua kategori berdasarkan saluran vestibular yang

mengalami kerusakan, yaitu:

1. Vertiga Periferal

Vertigo periferal terjadi jika terdapat gangguan di saluran yang disebut kanalis semisirkularis,
yaitu telinga bagian tengah yang bertugas mengontrol keseimbangan. Gangguan kesehatan
yang berhubungan dengan vertigo periferal antara lain penyakit seperti benign parozysmal
positional vertigo (gangguan akibat kesalahan pengiriman pesan), penyakit meniere (gangguan
keseimbangan yang sering kali menyebabkan hilang pendengaran), vestibular neuritis
(peradangan pada sel-sel saraf keseimbangan), dan labyrinthitis (radang di bagian dalam
pendengaran).

2. Vertigo Sentral

Saluran vestibular adalah salah satu organ bagian dalam telinga yang senantiasa mengirimkan
informasi tentang posisi tubuh ke otak untuk menjaga keseimbangan. Vertigo sentral terjadi jika
ada sesuatu yang tidak normal di dalam otak, khususnya di bagian saraf keseimbangan, yaitu
daerah percabangan otak dan serebelum (otak kecil).

Vertigo timbul jika terdapat gangguan alat keseimbangan tubuh yang mengakibatkan
ketidakcocokan antara posisi tubuh (informasi aferen) yang sebenarnya dengan apa yang
dipersepsi oleh susunan saraf pusat (pusat kesadaran). Susunan aferen yang terpenting dalam
sistem ini adalah susunan vestibuler, sistem optic (nerve 3,6) dan pro-prioseptik.

Dalam kondisi fisiologis/normal, informasi yang tiba di pusat integrasi alat keseimbangan tubuh
berasal dari reseptor vestibuler, visual dan proprioseptik kanan dan kiri akan diperbandingkan,
jika semuanya dalam keadaan sinkron dan wajar, akan diproses lebih lanjut. Respons yang
muncul berupa penyesuaian otot-otot mata dan penggerak tubuh dalam keadaan bergerak. Di
samping itu orang menyadari posisi kepala dan tubuhnya terhadap lingkungan sekitar. Jika
fungsi alat keseimbangan tubuh di perifer atau sentral dalam kondisi tidak normal/ tidak
fisiologis, atau ada rangsang gerakan yang aneh atau berlebihan, maka proses pengolahan
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informasi akan terganggu, akibatnya muncul gejala vertigo dan gejala otonom. Di samping itu,
respons penyesuaian otot menjadi tidak adekuat sehingga muncul gerakan abnormal yang
dapat berupa nistagmus, unsteadiness, ataksia saat berdiri/ berjalan dan gejala lainnya

Ada beberapa teori yang berusaha menerangkan kejadian ketidakseimbangan tubuh:

1. Teori rangsang berlebihan (overstimulation)

Teori ini berdasarkan asumsi bahwa rangsang yang berlebihan menyebabkan hiperemi kanalis
semisirkularis sehingga fungsinya terganggu; akibatnya akan timbul vertigo, nistagmus, mual dan muntah.

2. Teori konflik sensorik

Menurut teori ini terjadi ketidakcocokan masukan sensorik yang berasal dari berbagai
reseptor sensorik perifer yaitu antara mata/visus, vestibulum dan proprioseptik, atau
ketidakseimbangan/asimetri masukan sensorik dari sisi kiri dan kanan. Ketidakcocokan
tersebut menimbulkan kebingungan sensorik di sentral sehingga timbul respons yang dapat.

6. Explain the anatomy of cerebellum and its role on equilibrium and coordination

The cerebellum is located in the posterior fossa of the skull, dorsal to the pons and medulla
from which it is separated by the Aqueduct of Sylvius and the fourth ventricle.

Like the cerebrum, the cerebellum is covered by cortex and consists of two hemispheres, each
of which is divided into lobes. The hemispheres are separated from one another by a thin
structure called the vermis.

The anterior lobe, or paleocerebellum, is the second oldest part of the cerebellum. It receives
proprioceptive input from the spinal cord and controls the anti-gravity muscles of the body,
thus regulating posture.

The posterior lobe, or neocerebellum, is the newest part of the cerebellum. It is involved in the
coordination of muscle movement via the inhibition of involuntary movement. Inhibitory
neurotransmitters, especially GABA, are found here. This lobe plays an important role in fine
motor coordination.

The flocculonodular lobe consists of the flocculi, the most ancient part of the cerebellum, and
the nodulus, the narrowest and most inferior part of the vermis. This lobe is involved in the
maintenance of equilibrium.

Four different nuclei are located deep within each cerebellar hemisphere; the dentate nucleus,
the emboliform nucleus, the globose nucleus, and the fastigal nucleus. These deep nuclei
have axons that project to the brain stem, sending messages out to be conveyed to other parts
of the central nervous system.

The deep nuclei are regulated by radish-shaped cells located in the cerebellar cortex called
Purkinje cells. The Purkinje cells control the output of the cerebellum by inhibiting the firing of the
deep nuclei. The Purkinje cells located in the lateral cortex of the cerebellum project to the dentate
nuclei, while those in the intermediate cortex synapse with the emboliform and globose nuclei. The
fastigial nuclei receive input from Purkinje cells found in the cerebellar cortical covering of the
vermis

Case Objectives

1. Describe the neuroanatomy of the brainstem including major tracts and 12 cranial nerves which
arise from brain stem, and cerebellum
 WO 1
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2. Describe the location of nuclei of cranial nerves on brainstem and function of each 12 cranial
nerves 
 WO 2

3. Describe the correlation of the clinical findings with specific lesions in the brainstem and
cerebellum
 WO 3

Clinical Presentation of Cerebellar

The cerebellum connects widely in the neuraxis (brainstem, spinal cord, and nearly all areas of the cerebral
cortex) to aid in coordinating voluntary movement. The cerebellum also plays a key role in balance and eye
movements. Clinically, disorders of the cerebellum can be divided into those that affect the hemispheres,
and those at the affect midline structures, the latter including the vermis and the floculonodular lobe.

Clinical Signs of Disease in the Cerebellar Hemispheres

A lesion in one cerebellar hemisphere will cause motor deficits on the ipsilateral side of the body. This is
due to the “double cross” (i.e., input fibers cross to reach the cerebellum, and cerebellar output fibers
cross to reach their destination). In general a lesion in the cerebellar hemisphere results in a deterioration
of coordinated movements, or a decomposition of movement. The cerebellar hemispheres influence the
planning and control of precise movements of the extremities and in the timing of these movements.
 Dysmetria. Patients will past-point (i.e., reach past a target, or fall short of the target) 
 Tremor. The tremor in cerebellar disorders is an action intention tremor (i.e., it is brought out by
voluntary movement). Characteristically, the tremor is 1) more pronounced as the patient
approaches the endpoint; 2) is a proximal tremor (i.e., affects the shoulder and hip girdles
muscles predominantly); and 3) the direction of the tremor is perpendicular to the movement of the
limb. Tremor is test with the finger-to-nose and heel-to-skin (see figure above) tests. Note that at
rest there will be little or no tremor. 

 Dysdiadochokinesia (a.k.a., impaired rapid alternating movements). There will be

fragmentation and slowing of the movement as well as inaccuracy when performing rapid
alternating movements.
 Rebound phenomena. This is also known as an impaired check, or an inability of muscles to
adapt to rapid changes in load. For example, if the patient is pushing against the doctor's hand
and then the hand is pulled away unexpectedly, the patient's arm will overshoot where it would
normally stop. 
 Dysarthria. The speech is described a scanning. It is essentially ataxia of speech. Often the
pitch or rhythm of the speech will change. Grammar and word usage will still be correct. 
 Nystagmus. Patients often display nystagmus, often bilateral. 
 Unsteady gait. Patients will have an unsteady gait and a tendency to lean or even fall to the side
of the lesion. This will be due to ataxia involving the lower extremities (not the truncal ataxia with
vermis lesions.

Clinical Signs of Disease in the Cerebellar Vermis, Including the Floculonodular Lobe:
Lesions to this section of the cerebellar midline will result in bilateral deficits. The structures of the vermis
influence posture, balance, and equilibrium. This occurs through the vestibulospinal and reticulospinal
projections to extensor motor neurons of the axial and proximal limb muscles.

 Severe Gait Ataxia. The patient will have an unsteady, lurching gait. The patient may have
exaggerated movement of the legs and a tendency to fall to the side, forward, or backward. The
stance itself will be wide-based. This patient will be unable to do a tandem gait (heel-toe-heel-
toe), walk on their heels, or walk on their toes. 
 Titubation. This is essentially a tremor of the axial body or head. This can be as severe as
causing the patient to be unable to sit or stand unsupported. 
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 Nystagmus. This is most prominent especially if the flocculonodular lobe is involved. If present,
it will be maximal towards the side of the lesion. 

Nonspecific Findings Associated with Cerebellar Lesions

 Hypotonia. on the ipsilateral side (this is often mild or difficult to appreciate) 
 Vomiting. Vomiting can be seen in both disease of the vermis and of the hemispheres. In this
setting, the characteristics of the vomiting are important, particularly with cerebellar tumors.
There are three "P's" of vomiting with cerebellar disease: 1) Postural. Patients will complain of
vomiting associated with a certain position; 2) Positional. Patients will note that suddenly
changing position, particularly when sitting up quickly, brings on the vomiting; and 3) Projectile.
Often, the vomiting occurs very suddenly without nausea and thus tends to be projectile.

4. Review the physiology of cell cycles and pathophysiology of neoplasm development in brain and
meninges

The cell cycle is the sequence of events that take place to enable DNA replication and cell division. It can
be divided into two phases: interphase and mitosis. Interphase is further divided into the G1 (gap 1), S
(synthesis), and G2 (gap 2) phases, which prepare the cell for division. In mitosis, the single cell is dividing
into two identical daughter cells. The cell cycle is subject to strict controls that prevent cells with damaged
or faulty DNA from further dividing and passing on defects to daughter cells. Controlled cell death
(apoptosis) is initiated if the DNA damage is irreparable. Disorders of these regulatory mechanisms play an
important role in carcinogenesis.

Tumors of the brain produce neurologic manifestations through a number of mechanisms. Small, critically
located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or
supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited
volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased
intracranial pressure. Tumors adjacent to the third and fourth ventricles may impede the flow of
cerebrospinal fluid, leading to obstructive hydrocephalus. In addition, tumors generate new blood vessels
(ie, angiogenesis), disrupting the normal blood-brain barrier and promoting edema. The cumulative effects
of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (ICP) and impair
cerebral perfusion. Intracranial compartmental rise in ICP may provoke shifting or herniation of tissue under
the falx cerebri, through the tentorium cerebelli, or through the foramen magnum. Slow-growing tumors,
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particularly tumors expanding in the so-called silent areas of the brain, such as the frontal lobe, may be
associated with a more insidious clinical course. These tumors tend to be larger at detection. Most primary
brain tumors do not metastasize, but if they do metastasize, intracranial spread generally precedes distant
dissemination. Metastatic brain tumors from non-CNS primary tumors may be the first sign of malignancy,
or they may herald a relapse. Nonetheless, the signs and symptoms of brain metastases simulate those of
primary brain tumors. Leptomeningeal infiltration may present with dysfunction of multiple cranial nerves

Although few factors are unequivocally associated with an increased risk of brain cancer, most CNS
neoplasms are thought to arise from individual cell mutations. A few inherited diseases, such as
neurofibromatosis, tuberous sclerosis, multiple endocrine neoplasia (type 1), and retinoblastoma, increase
the predilection to develop CNS tumors. Primary CNS lymphoma is a relatively frequent occurrence in HIV
patients. A prior history of irradiation to the head for reasons other than treatment of the present tumor may
increase the chance of primary brain tumor. The most common tumors originating from the
cerebellopontine angle are acoustic neuroma and meningioma. Metastatic tumors reach the brain via
hematogenous dissemination through the arterial system. Lung cancer is by far the most common solid
tumor disseminating to the brain, followed by breast, melanoma, and colon cancer. Less common sources
of metastasis are malignant melanoma, testicular cancer, and renal cell cancer. Prostate, uterine, and
ovarian cancers are unlikely sources of brain metastasis.

5. Describe the classification of meningioma and its grading systems related to anatomical
pathology findings
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Clinical presentation
The presentation of meningiomas, like other CNS tumors, depends upon their location. Meningiomas can
be found arising from any intracranial or spinal dural surface. Rarely, intraventricular meningiomas are
identified. Meningiomas are typically not fast growing or infiltrative lesions, and they have an insidious
symptom onset. Many are discovered incidentally on brain imaging. While there is no pathognomonic
presentation of meningioma, clinical symptoms of headache due to increased intracranial pressure, focal
neurological (including cranial nerve) deficits or generalized and partial seizures caused by focal mass
effect, are typical. Personality changes, confusion and altered level of consciousness can be seen,
especially in anterior (frontal) or parasagittal meningiomas, and they may be initially misdiagnosed as
dementia or depression. The differential diagnosis of a patient presenting with such symptoms is quite
broad and should include other intracranial lesions (such a glioma or metastatic tumors).

6. Describe the basic principles of management in intracranial tumor cases, particularly

meningioma
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A variety of therapies are used to treat brain tumors. The type of treatment recommended depends on the
size and type of the tumor, its growth rate, brain location, and the general health of the patient. Treatment
options include surgery, radiation therapy, chemotherapy, targeted biological agents, or a combination of
these. Surgical resection (if safe) is generally the first treatment recommendation to reduce pressure in the
brain rapidly. This website focuses on radiation therapy for brain tumors.
In the past two decades, researchers have developed new techniques of delivering radiation that target the
brain tumor while protecting nearby healthy tissues. These treatments include brachytherapy, intensity-
modulated radiation therapy (IMRT) and radiosurgery.
Radiation therapy may be advised for tumors that are sensitive to this treatment. Conventional radiation
therapy uses external beams of x-rays, gamma rays or protons aimed at the tumor to kill cancer cells and
shrink brain tumors. The therapy is usually given over a period of several weeks. Whole brain radiation
therapy is an option in the case of multiple tumors or tumors that cannot be easily targeted with focal
treatment.

Types of radiation therapy include:

 Intensity-modulated radiation therapy (IMRT): an advanced mode of high-precision radiotherapy
that utilizes computer-controlled x-ray accelerators to deliver precise radiation doses to a malignant
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tumor or specific areas within the tumor. The radiation dose is designed to conform to the three-
dimensional (3-D) shape of the tumor by modulating—or controlling—the intensity of the radiation
beam to focus a higher radiation dose to the tumor while minimizing radiation exposure to healthy
cells. See the IMRT page for more information.
 Stereotactic radiosurgery (SRS): a highly precise form of radiation therapy that directs narrow
beams of radiation to the tumor from different angles. For this procedure, the patient may wear a
rigid head frame. Computed tomography (CT) or magnetic resonance imaging (MRI) help the doctor
identify the tumor's exact location and a computer helps the doctor regulate the dose of radiation.
Stereotactic radiotherapy is similar physically to radiosurgery but involves fractionation (multiple
treatments). This modality would be recommended for tumors within or close to critical structures in
the brain that cannot tolerate a large single dose of radiation or for larger tumors. See
the Stereotactic radiosurgery page.
 Three-dimensional conformal radiation therapy (3D-CRT): a conventional form of radiation treatment
delivery that uses a specific arrangement of x-ray beams designed to conform to the shape of the
tumor to maximize tumor dose and minimize normal surrounding tissue dose. This form of treatment
is tailored to the patient's specific anatomy and tumor location. CT and/or MRI scan is often required
for treatment planning.
 Brachytherapy: the temporary placement of radioactive source(s) within the body, usually employed
to give an extra dose—or boost—of radiation to the area of the excision site or to any residual
tumor. 

Surgery, also called surgical resection, is often indicated for primary brain tumors. A surgeon removes
some or the entire tumor without causing severe damage to surrounding tissues. Surgery may also be used
to reduce pressure within the skull (called intracranial pressure) and to relieve symptoms (called palliative
treatment) in cases when the tumor cannot be removed.

Chemotherapy, or anticancer medications, may be recommended. Chemotherapy, along with radiation

(concurrent therapy), has become the standard of care for primary malignant brain tumors. The use of
these drugs or chemicals to slow down or kill rapidly dividing cells can be used before, during, or after
surgery and/or radiotherapy to help destroy tumor cells and to prevent them from returning. Chemotherapy
drugs may be taken by pill or by injection and are often used in combination with radiation therapy. Drugs
called radiosensitizers, which are believed to make radiation therapy more effective, may also be
prescribed.