Download Session 7: Neoplastic & Autoimmune CNS Disorders

Session 7:
Neoplastic & Autoimmune CNS Disorders
Vignette
A 23 yo med student with a 2 day history of
headache, blurred/darker vision/loss of vivid
color. There is accompanying left retroorbital pain which worsens with eye
movement. She has never had anything like
this before, and past medical history is
negative.
• Anatomical localization?
Questions
• Exam: L eye 20/100; R 20/20; L disc is
edematous; pupils are equal but when light is
shined into L eye pupils are 4mm; and 2 mm
when shined into R eye. R gaze: L eye adducts
more slowly than the R eye. L gaze eyes are
conjugate. Enlarged blind spot noted on the L.
• Does the examination refute or support
localization?
• Cause for visual impairment
Questions
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Visual acuity
Light reaction
Eye movements
Visual fields
Cause of visual impairment
Cause of eye movement difficulties
Questions
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ROS
PMHx
Tests
Diagnosis
Certainty and how is diagnosis is made
What is the outlook?
What do you disclose?
MRI Scans of the Brain of a 25Year-Old Woman with
Relapsing–Remitting Multiple
Sclerosis.
An axial FLAIR (fluid-attenuated
inversion recovery) image shows
multiple ovoid and confluent
hyperintense lesions in the
periventricular white matter (Panel
A). Nine months later, the number
and size of the lesions have
substantially increased (Panel B).
After the administration of
gadolinium, many of the lesions
demonstrate ring or peripheral
enhancement, indicating the
breakdown of the blood–brain
barrier (Panel C). In Panel D, a
parasagittal T1-weighted MRI scan
shows multiple regions in which the
signal is diminished (referred to as
"black holes") in the periventricular
white matter and corpus callosum.
These regions correspond to the
chronic lesions of multiple sclerosis.
Multiple sclerosis: This 35-year-old woman with a history of migraine headaches
presented with a two-week history of slurred speech and trouble walking. Her
examination was significant for slight left hemiparesis, brisk jaw jerk and bilateral
hyperreflexia. Laboratory data demonstrated oligoclonal banding in the cerebrospinal
fluid. These FLAIR-weighted axial MR images show multiple high signal lesions
within the periventricular white matter. On the sagittal image on the right the signals
emanate radially from the corpus callosum.
Optic Neuritis with a swollen optic nerve
Optic atrophy
The optic disc is pale. Note: if the patient
is pseudophakic in one eye and has
cataract in the other, the disc in the
pseudophakic eye may appear paler in
the absence of optic atrophy.
The following features may help in the
diagnosis.
•Excavated appearance with the blood
vessels dipping the edge (glaucoma)
•Indistinct edge with glial tissue (chronic
papilloedema)
•Well-defined edge without excavation (optic
nerve disease)
Look for:
in young patient: internuclear
ophthalmoplegia and cerebellar sign for
multiple sclerosis; in old patient, look for
vascular diseases such as prominent
temporal artery (or old scar indicating
temporal artery biopsy) and carotid bruit
(or endarterectomy scar)
Relative afferent pupillary defect
The arrows represent the light.
This is a common case in pupillary examination.
Always suspect this if there is no anisocoria.
The direct and consensual pupillary responses to light
are normal. The swinging light test shows abnormal light
response of the affected eye (initial dilatation followed by
constriction). For example, if the left eye were
abnormal, both pupils constrict when the light is
shown into the right eye. When the light is swung to
the left eye, both pupils dilate. When the light is swung
back to the right eye both pupils again constrict. This
reaction indicates a defect in the afferent pupillary fibres
from the left eye. The near reflex is normal.
Further examination:
tell the examiner that you would like to examine the
fundus of the affected eye. The most common physical
signs would be optic atrophy. Other possibilities include
advanced glaucoma, retinitis pigmentosa, old central
retinal artery or vein occlusion.
A patient with a left relative afferent pupillary defect.
Fig.1 A patient with a right dilated and unreactive pupil.
The swinging flash test shows abnormality of the left eye.
(Note the dilatation of the left eye when the light is swung to the left.)
Fig. 2 A patient with a right dilated and unreactive pupil.
The swinging flash test shows abnormality of the right eye
(Note dilatation of the left eye when the light is swung to the right).
Left internuclear ophthalmoplegia
R
L
The most common scenario in the examination is young female with
history of multiple sclerosis. However, it can also be seen in older patients
with cerebrovascular accident. The main feature of this condition is
impaired adduction. A favourite question is the site and side of the lesion
(see question below).
In unilateral case, the affected eye shows failure (or impaired) adduction (failure
of conjugate eye movement). The abducting eye shows jerk nystagmus with the
quick phase towards the opposite side (this is called ataxic nystagmus but may
not be obvious and can be absent). The horizontal saccade is abnormal with the
affected eye lagging behind the normal eye. The vertical saccade and
convergence are normal.
Internuclear ophthalmoplegia (INO)
a. Normal primary position
c. Normal left abduction on left gaze
b. Left impaired adductionn on right gaze
d. Normal convergence
Impact on Visual Fields
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Left optic nerve lesion
Optic chiasmal lesion
Left temporal lobe lesion
Left occipital lobe lesion
Visual
Pathways
1. Central scotoma resulting
from inflammation of the
optic disc
2. Junctional scotoma
3. Bitemporal hemianopia
resulting from a lesion
around the optic chiasm
4. Incongruous homonymous
hemianopia resulting
from a lesion in the optic
tract
5. Homonymous quadrinopia
resulting from a lesion in
the temporal lobe
6. Homonymous hemianopia
resulting from a lesion in
the occipital lobe.
1. Central scotoma resulting from
inflammation of the optic disc
The peripheral visual fields are
normal in both eyes. There is a
right central scotoma (revealed by
testing the central field with a red
pin). Note: the most likely
diagnosis is optic neuritis.
Further examination:
•Examine the patient's fundus for
any evidence of papillitis or optic
atrophy. Also check for relative
afferent pupillary defect.
•Look for cerebellar signs or
spastic paresis which are
common in patients with multiple
sclerosis.
2. Junctional scotoma
The patient has a right central
scotoma and left superior temporal
field defect. This suggests a lesion
between the optic nerve and the
chiasm on the side with the central
scotoma. There is compression of the
knee of Wilbrand (loop of inferior
nasal fibers) that enter the
contralateral optic n for a short
distance before travelling in the optic
tract. Examine for optic atrophy on
the side with central scotoma and
possible papilloedema on the other
side. The most common causes are
meningioma and a prefixed pituitary
tumour. In the former, the patient may
have proptosis and in the later signs
of hypopituitarism or acromegaly.
3. Bitemporal hemianopia resulting
from lesion around the optic chiasm
There is bitemporal hemianopia which
obeys the midline.and suggests a lesion
in the optic chiasm. The hemianopia
may be subtle and revealed only by
comparing two red objects in each
hemifield. The red color in the temporal
field appears washed out. If the
hemianopia does not obey midline
consider pseudo-bitemporal hemianopia
such as bilateral sectorial retinitis
pigmentosa, tilted discs or bilateral
inferotemopral retinoschisis. Examine
the fundi for any such changes.
Features of pituitary abnormalities such
as acromegaly, pan-hypopituitarism
(smooth skin and absence body hair in
male) Look for any scar suggestive of
pituitary operation.
4. Incongruous homonymous
hemianopia resulting from lesion
in the optic tract
The patient has a left incongrous
homonymous hemianopia suggesting
lesion in the right optic tract. Optic
tract lesion causes homonymous
hemianopia which is incongrous
(meaning that the shape of the defect
is different in the two half fields). This
can be established on confrontation if
significant. If subtle it is best
documented with formal field test.
In the examination, optic tract lesions
are often associated with
contralateral pyramidal signs (due to
damage to the cerebral peduncle).
5. Homonymous quadrinopia
from lesion in the temporal lobe
Left superior homonymous quadrinopia
Left inferior homonymous quadrinopia
The optic radiations are in the temporal
and parietal lobes. A left superior
homonymous quadrinopia is associated
with a temporal lobe lesion whereas a
left inferior homonymous quadrinopia is
seen with a parietal lobe lesion. During
examination describe the visual field as
the patient sees it. Mention if the field
defect is congruous (behind the lateral
geniculate body) or incongruous (in the
optic tract). Look for other neurological
signs such as hemiplegia.
If the patient has a right inferior quadrinopia, you should consider
Gertmann's syndrome if the lesion is in their dominant parietal lobe.
What is Gertmann's syndrome?
Failure of the person to calculate (acalculia), name fingers (finger
agnosia), and to tell right from left
In patients with hemianopia or inferior quadrinopia, mention you like to
perform the optico-kinetic drum test for evidence of parietal lobe
lesion. What abnormality may you see? Impaired pursuit to the side of
the parietal lobe lesion.
Normal opticokinetic nystagmus with
smooth pursuit movement.
Abnormal opticokinetic nystagmus with
small saccadic movement replacement the
smooth pursuit movement.
Which other higher sensory perceptions are impaired
Astereoagnosia (failure to tell an object through touch)
Joint position sense loss and loss of two point discrimination
How do you test for sensory inattention?
With the patient’s eyes closed alternatively touch
the patient’s right then left hand (to ascertain that
primary sensory function is intact) and then touch
both hands simultaneously. If there is sensory
inattention (neglect) the individual will only notice
the touch on one side when touched
simultaneously.
Demonstrate a central scotoma
Impact on a Rightward Saccade
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Left middle cerebral artery infarct
Left frontal lobe seizure
Right pontine infarct
Left medial longitudinal fasisculus lacune
Left diabetic third nerve palsy
Movement
Saccade
Pursuit
Oculovestibular
Convergence
Definition
Associated structure
1) Saccade
2) Pursuit
Function: to keep the fovea on a small moving target, e.g. tracking a
tennis ball.
As in saccades, pointing the fovea at this moving ball is a 2D
problem.
3) Vestibular ocular reflex/ Oculovestibular reflex
Function: to keep the image of the world stationary on the retina
when the head rotates. Try shaking your head while reading this
sentence. The fact that you can do this means that your VOR is
working, it is keeping your eye still in space.
It does this by rotating the eyes in the opposite direction of the head.
4) Vergence/convergence
Function: to align a near target on the fovea of each eye.
Vertical Saccade
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Vertical saccades originate from burst
neurons in the rostral interstitial
nucleus of the medial longitudinal
fasciculus (riMLF).
The riMLF, like PPRF, produces the
phasic command.
Neurons in the interstitial nucleus
(INC) convert this to a tonic command
(like the pph for horizontal saccades).
The phasic and tonic commands
combine in the MN's in III & IV n.
Both sides of the brainstem have
neurons that generate upward
saccades and others that generate
downward saccades.
Do neurons on each side do the same
thing; i.e. is this a redundant
representation?
Horizontal saccades
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Saccades are one of 5 types of eye
movements. They are used to point your
fovea quickly from one object of interest to
another, such as the words of this
sentence.
The command for a saccade begins in a
structure called the Paramadian Pontine
Reticular Formation; the PPRF
Burst neurons in the PPRF generate
phasic movement command which is
proportional to velocity
Tonic neurons in prepositus hypoglossi
(PPH)
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converts the phasic command to a tonic
command
this is like an integrator which converts
velocity to position
Motorneurons (MN's) combine phasic and
tonic commands
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this contracts muscles
quickly rotates the eyes (phasic
component)
& then holds (tonic component) them there
against the elastic restoring forces.
Vestibular Control of Eye Movements
Questions
III
IV
V1
V2
VI
Contents of the cavernous sinus (red)
A. Carotid Artery
B. Trochlear Nerve IV
C. Maxillary Nerve V2
D. Abducens Nerve VI
E. Sphenoid Sinus
F. Pituitary Gland
G. Cavernous Sinus
H. Ophthalmic Nerve V1
I. Oculomotor Nerve III
Carotid-Cavernous sinus fistula
- Horner's syndrome + cranial nerve 3 and/or 4 and/or 6 and/or V1/V2 dysfunction
(and not affecting V3) => suspect cavernous sinus pathology
- Horner's syndrome + cranial nerves 3 and/or 4 and/or 6 and/or V1 (and not affecting
V2 and V3) dysfunction => suspect superior orbital fissure pathology
- Horner's syndrome + cranial nerves 2 (optic nerve), 3, and/or 4 and/or 6 and V1
(and not affecting V2 and V3) dysfunction => suspect orbital apex pathology
- Horner's syndrome + optic nerve II dysfunction +/- incomplete cranial nerve 3
dysfunction (and not affecting cranial nerves 3, 4 and 6 and V2 and V3) => suspect
posterior orbit pathology
- all patients with an asymptomatic,
unexplained Horner's syndrome (especially
if they have ipsilateral anhidrosis of the face
and neck, which implies a preganglionic
Horner's syndrome), who are going to be
discharged from the ED for pre-arranged
follow-up as an outpatient, should have a
chest X-ray performed prior to ED
discharge - to exclude a mediastinal or
apical lung tumor (Pancoast's tumor) or
thoracic aneurysm affecting the second
neuron
Structural Abnormality
Orbit
Superior orbital fissure
Cavernous sinus
Upper brainstem
Autonomic Pupillary Innervation
• Sympathetic (Horner syndrome)
• Parasympathetic (IIIrd nerve)
For patients with a normal light reaction and whose anisocoria is greatest in the
dark => the smaller pupil in the dark is the abnormal pupil (dilation problem with
the smaller pupil)
Differentiation between physiological
anisocoria and Horner's syndrome
Unexplained unilateral Horner's syndrome
+ face/head pain is a carotid artery
dissection until proved otherwise
Right Horner’s syndrome:
Ptosis
Miosis
Anhydrosis
Vasodilatation
Causes of Horner's syndrome
Central
Hypothalamus
- infarct
- tumor
Brainstem
- ischemia
- hemorrhage
- tumor
- demyelination (MS)
Cervical cord
- trauma
- tumor
- syrinx
- AVM
Preganglionic
Postganglionic
Cervico-thoracic spinal roots
- trauma
- intramedullary or paravertebral tumor
- syrinx
- AVM
- spondylosis
- epidural anesthesia
Lower brachial plexus
- birth trauma
- acquired trauma
Pulmonary apex (under subclavian artery)
- vascular anomalies
- Pancoast's apical lung tumor
- cervical rib
- iatrogenic (chest tube, central catheter)
- infection (eg. apical TB)
Anterior neck
- iatrogenic (thyroid or neck surgery)
- trauma
- tumor
Superior cervical ganglion
- iatrogenic (tonsillectomy)
- trauma
Internal carotid artery
- dissection
- trauma
- thrombosis
- tumor
- cluster headache
Base of skull/carotid canal
- tumor (nasopharyngeal CA)
- trauma
Middle ear
- tumor (cholesteatoma)
- infection
Cavernous sinus
- tumor (pitutary adenoma)
- inflammation (Tolosa Hunt)
- cavernous carotid aneurysm
- thrombosis
- fistula
Clinical Pearls
- if there is a ptosis of the eyelid on the side of the small pupil => the patient has a
Horner's syndrome on that side
- if there is a ptosis of the eyelid on the side of the large pupil => the patient has a partial
third nerve lesion on that side
- with a lesion in the region of the cavernous sinus, there may actually be a reversal of
the anisocoria in going from dark to light as a result of unilateral involvement of both
parasympathetic and sympathetic axons
- a patient with a very small unilateral miotic pupil, that does not decrease in size in
response to direct bright light, or dilate in response to dim light => probably has unilateral
pharmacolgical miosis secondary to a cholinergic glaucoma drug (eg. pilocarpine) or an
anti-cholinesterase agent ("flea collar" anisocoria)
- a mydriatic pupil that does not respond to light may appear to be due to 3rd cranial nerve
pathology, but it could just be a tonic pupil - the only difference between the two may be
that the tonic pupil does eventually constrict slowly on prolonged near fixation
- a patient with uncal herniation causing a compressive 3rd cranial nerve palsy, always
has some degree of impairment of LOC and is never fully alert
- a patient with "apparent" physiological anisocoria may have simple anisocoria
secondary to the effect of certain drugs eg. pseudo-ephedrine or serotonin reuptake
inhibitors, and the anisocoria (like physiological anisocoria) is also eliminated by the
instillation of cocaine eyedrops
- blindness in one eye (even if total) never causes anisocoria
- retinal pathology (even if very severe) never causes anisocoria
Pupil sparing CN III palsy suggests diabetes.
For patients with an abnormal light reaction and whose anisocoria is
greatest in bright light conditions => the larger pupil is the abnormal
pupil (constriction problem with the larger pupil)
Left IIIrd nerve palsy
Left IIIrd nerve palsy
Vignette
An 86 year old man has come to your clinic for an
evaluation of back pain. He has had prostate cancer for
two years. His back pain has been present for weeks "off
and on", but has started to shoot across the right side of
his back, below the rib cage. In the last few days, he has
noticed some numbness of the left leg. He does very
little walking, but can walk between rooms in his
apartment with help. Some urinary symptoms date back
years; he is continent. He says he has already told his
primary care physician that he does not want aggressive
treatment when "the inevitable" happens.
• The physical examination reveals a lucid but
very frail man, who can rise from a chair and
take several steps only with considerable
help. His gait is not noticeably asymmetric.
There is tenderness over the T10 vertebra.
Although he is frail, strength is full except for
mild right lower extremity weakness. The
DTRs in the arms are symmetric, the right
knee reflex is greater than the left and ankle
reflexes are absent bilaterally. There is a
positive Babinski sign on the right, not on the
left. Sensation to pin is diminished in the left
leg, up to about mid-thigh in front and through
the perineal area in back.
• What is the anatomic diagnosis?
• How do you account for the differing laterality
of motor (reflex) and sensory signs, and what
is this called?
• What process is involved? What would be
your differential diagnosis for this kind of
deficit if the patient had not had a history of
cancer?
• What imaging tests are available for the area
you wish to investigate, and what are their
uses? Which would you pick for this patient?
• What treatments are available?
• How urgent is evaluation and
treatment? Would your approach be different
if there were back pain without neurological
signs?
Vignette
• A 34 year old man develops gait difficulty
and numbness below the mid-chest 2
weeks after an upper respiratory illness.
Examination demonstrates diminished pin
sensitivity below the mid-chest, absent
abdominal reflexes, sustained ankle
clonus and bilateral Babinski signs. He
has a spastic gait.
Brown Sequard
Muscles: -no muscle control on the same side of the body that the lesion occurred
Sensation: -no sensation of “touch” on the same side of the body that the lesion occurred -no pain and
temperature sensation on the opposite side of the body that the lesion occurred
Other: -fairly often have normal bowel and bladder functioning
Anterior Cord
Muscles: -variable muscle control throughout body Sensation: -variable sensation of touch, temperature
and pain throughout body, however can sense where limbs are in space
Central Cord
Muscles: -upper limbs are weaker than lower limbs Sensation: -maintain most sensations Other: -this
injury usually occurs in the cervical region
Posterior Cord
Muscles: -can control most muscles throughout bodySensation: - no sensation of touch, temperature
and pain
Cauda Equina
Muscles: -no muscle movement in certain muscles in the lower limb Other: -may cause incontinence-this part of the
spinal cord is actually made of nerves, nerves (unlike the spinal cord) have the ability to heal and therefore there is a
chance that some muscle control will return after a cauda equina injury (This is an injury to the nerves that exit at the
base of the spinal cord)
High signal change in spinal cord on T2 weighted MRI
Vignette
• A 57 year old man develops gradually
progressive left-sided headaches
clumsiness in the right hand over 6
months’ time. Examination demonstrates
moderate slowing of rapid repetitive
movements in the right hand and foot, 3+
reflexes throughout the right and 2+
reflexes throughout the left.
Vignette
• A 67 year old woman with a history of
breast cancer develops progressive leftsided headaches and clumsiness in the
right hand over 6 weeks’ time and loss of
appetite. Examination demonstrates mild
attentional difficulty, a left homonymous
hemianopsia, moderate slowing of rapid
repetitive movements in the right hand and
foot, and bilateral Babinski signs.
Brain Metastasis - Lung Carcinoma Right Frontal Lobe
Enhanced CT shows 3 cm mass right frontal region with extensive vasogenic
white matter edema with mass effect, midline shift.
Vignette
• A 31 year old woman with fever, anemia,
and a facial rash is admitted to the hospital
with an acute confusional state.
Vignette
• A 36 year old woman develops a Bell’s
palsy for the second time in 9 months with
headache and unilateral hearing loss.
Examination demonstrates a right facial
palsy, left sided hearing loss, and patchy
hyporeflexia; chest x-ray demonstrates
hilar adenopathy.
Vignettes
• Idiopathic intracranial hypertension
• Cerebral venous thrombosis
77 year old male with decreased
libido
Findings
T1 sagittal image shows a
heterogenous mass centered
primarily in the sella with large
suprasellar extension. T2 coronal
image shows predominantly
hypointense signal in this mass.
Post contrast coronal image
shows heterogenous
enhancement and extension of
this mass into right cavernous
sinus.
Diagnosis: Pituitary Prolactinoma
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Reference: Diagnostic
Neuroradiology, Anne G. Osborn
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Contributor: Harish Patel , M.D
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Discussion
Common intrasellar masses include
physiologic hyperplasia, microadenoma
and nonneoplastic cyst { Rahtke's cleft cyst
}. Of these, none fit the description of this
extensive mass. The list can be long to
include suprasellar lesions like
meningioma, craniopharyngioma, pituitary
macroadenoma, hypothalamic/chiasmatic
glioma and aneurysm
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Prolactinomas are the most common
pituitary adenomas, accounting for about
30%. They occur in young women causing
amenorrhea and galactorrhea, and in
elderly male causing decreased libido.
Patients have elevated serum prolactin
levels as in this case. This study was
performed for a follow up evaluation after
Bromocriptine therapy . Bromocriptine is
the medical treatment and often shows size
reduction within a week of therapy.