AUTONOMIC PHENOMENA OF EYE , HORNER SYNDROME AND OCULOMOTR PALSY DIAGNOSIS AND LOCLAIZATION

1. AUTONOMIC EYE PHENOMENA
(3rd nerve palsy Vs. Horner syndrome)
diagnosis and localization
DR. MOHAMED ELSHAFEI
DR.LINK147@YAHOO.COM

2. OCULOMOTOR NERVE PARALYSIS

3. 1- introduction :
- Dysfunction of the third cranial nerve (oculomotor nerve)
can result from lesions anywhere along its path. between
the oculomotor nucleus in the midbrain and the
extraocular muscles within the orbit.
- The diagnosis and management of third nerve palsy varies
according to the age of the patient, characteristics of the
third nerve palsy, and the presence of associated signs
and symptoms.

4. 2- neuroanatomy :
* The third nerve begins as a nucleus in the midbrain
- that consists of several subnuclei that innervate the individual
extraocular muscles, the eyelids, and the pupils . Each subnucleus,
except the superior rectus subnucleus, supplies the ipsilateral muscle
- The superior rectus subnucleus  innervates the contralateral
superior rectus muscle
- The levator subnucleus  is a single central caudate nucleus and
innervates both levator palpebrae superioris muscles (which control
the eyelids)
- The parasympathetic pupil nucleus (Edinger-Westphal nuclei) 
controls pupil constriction
* The third nerve fascicle leaves the nucleus
- passes ventrally near important structures in the midbrain (eg, red
nucleus, corticospinal tract).
- The third nerve then enters the subarachnoid space, passes into the
lateral wall of the cavernous sinus, and finally divides into superior
and inferior branches as it enters the superior orbital fissure in the
orbit to innervate the extraocular muscle .
- The superior division of the third nerve supplies the levator
palpebrae and the superior rectus, while the inferior division
supplies the medial and inferior rectus muscles, the inferior oblique,
and the pupillary sphincter.
* Because the fibers are topographically organized within the third nerve
fascicle and nerve, a pattern of deficits that represents a divisional
palsy is not helpful in anatomic localization
Levator
subnucleus
superior rectus
subnucleus

5. 3- Etiology :
- Etiologies of third nerve palsies are specific to the location : see table!
* Intracranial aneurism :
- it`s the most dreaded cause mainly posterior cerebral artery aneurism , ICA aneurism & basilar A. aneurism.
- In the setting of an acute third nerve palsy, the aneurysm is believed to be acutely enlarging and therefore at risk of
imminent rupture. In this setting, subarachnoid hemorrhage can occur within hours or days of initial presentation of the
third nerve palsy (BAD SIGN)
* Ischemia :
- Ischemic third nerve palsies, also called diabetic third nerve palsies, are the most common etiologic subset of third nerve
palsy in adults.
- The pathogenesis is felt to be microvascular .
- risk factors: HTN, Old age
* Trauma :
- Traumatic third nerve palsy usually arises only from severe blows to the head, with skull fracture and/or loss of
consciousness.
- Thus, a third nerve palsy associated with mild head trauma should prompt evaluation for associated pathology.
* Migraine :
- Ophthalmoplegic 'migraine,' a condition affecting children and young adults,
- This most commonly affects the third cranial nerve, sometimes with permanent deficits .
- Several cases have been reported in which ophthalmoplegic 'migraine' is associated with MRI gadolinium enhancement of
the cisternal segment of the affected cranial nerve in patients with a typical clinical presentation, suggesting that the
condition may be a recurrent demyelinating neuropathy

6. 4- CLINICAL FEATURES :
1- symptoms :
- acute 3rd n. palsy 
- sudden onset of double vision and droopy eyelid + symptoms of the
cause.
- Pain :- mild to moderate  common in ischaemic lesions
severe pain  inflammatory lesion or pitutary apoplexy
sudden severe pain (the worst headache of my life)  suggest
subarachnoid hge d.t rupture aneurism
- chronic 3rd n. palsy  usually asymptomatic (espacially with 1ry apparent
regeneration).

7. 2- Examination :
- complete non pupil-sparing third nerve palsy:
* Pupil ( internal dysfunction ): large unreactive pupil,
* EOMs ( external dysfuction ) : have ptosis, paralysis of adduction,
elevation, and depression.
The eye rests in a position of abduction, slight depression, and
intorsion "down and out“.
- In partial lesions:
* Pupil : may be of normal size & reactive (no internal dysfunction),
dilated and poorly reactive (partial internal dysfunction), or dilated and
non-reactive to light and near stimulus (complete internal dysfunction).
=> The asymmetry of pupil size is greater in the light than in the dark.
* EOMs : may be complete or incomplete involvement  variable degrees
of ptosis & paresis.

10. 5- localization :
=> Clinical localization :
-see table.
- according to the presence of other neurologic deficits or systemic
symptoms, it`s classified to :
1- isolated : further classified as having normal internal function
(pupil-sparing) or abnormal internal function (non pupil-
sparing).
2- non-isolated

12. 1- NON - ISOLATED 3rd N. PALSY :
1 : midbrain lesion (nuclar & fascicular) :
- rare.
- Usually non isolated (are usually associated with other neurologic deficits
localized to the midbrain).
- Different patterns of nuclear lesion:
1- Complete ipsilateral third plus contralateral ptosis (as LPS ms hss single
subnucleus) and contralateral superior rectus weakness(because SR subnuclus
is crossed)
2- bilateral third nerve palsies with sparing of the eyelids
3- isolated bilateral ptosis with sparing of the extraocular muscles and pupils.
4- ipsilateral ptosis and contralateral eyelid retraction (plus-minus lid
syndrome) if supranuclear inhibitory input to the third nerve is disrupted and
ptosis from a fascicular lesion on the contralateral side occurs.
5- isolated extraocular muscle involvement. However, unilateral or bilateral
isolated medial rectus paralysis is unlikely to be caused by a nuclear lesion
because medial rectus neurons probably lie at three different locations within
the oculomotor nucleus. For this reason, patients with presumed isolated
medial rectus paresis should be evaluated for internuclear ophthalmoplegia.

13. - Nuclear lesions that are caused by infarction are often accompanied by
lesions of the third nerve fascicle because both structures are supplied
by the paramedian branches of the basilar artery.
- A nuclear or fascicular third nerve lesion almost always occurs with
other neurologic signs or symptoms, which identifies the midbrain
location of the lesion:
* Contralateral ataxia will be present if the red nucleus/superior
cerebellar peduncle is involved
* Cerebellar tremor may be present in Claude syndrome (ipsilateral
third nerve palsy and contralateral cerebellar signs)
* Contralateral hemiparesis may be present in a cerebral peduncle
lesion (Weber syndrome)
* Contralateral choreiform movements or tremor are present when red
nucleus/substantia nigra involvement occurs (Benedikt syndrome).
 DO MRI Brain.

14. 2- subarachnoid sapce :-
- Usually isolated
- inflammatory, infection, neoplastic causes  usually affect other CNs
- Ischemia  80-90% are pupillary sparing as pupillomotor fibers are
superficial
- aneurism  pupillary non-sparing + incomplete external dysfunction
- Signs of aberrant regeneration or oculomotor synkinesis are common
with lesions caused by nerve compression or after trauma and are rare
with ischemic lesions.
=> These signs include lid retraction with adduction or down-gaze,
globe retraction and/or adduction with attempted vertical gaze, and
pupil constriction with eye movement using third nerve-innervated
muscles.
- Spontaneous improvement of symptoms should not be reassuring in
regards to diagnosis; this has been described with aneurysmal lesions
 DO CT-BRAIN WITHOUT CONTRAST ( to exclude SAH )  if not
revealing ,
 DO LUMPAR PUNCTURE  if there`s no SAH,
 CTA or MRA ( to exclude unruptured aneurism ) must be done.

15. 3- cavernous sinus lesion:
- Usually involve :
* CN IV  vertical diplopia (look for lack of intorsion in downgaze in
a patient with complete third nerve palsy and possible fourth nerve
deficit)
* CN V (ophthalmic)  pain or numbness on the face.
* CN VI  horizontal diplopia; esotropia (inward deviation)
* Oculosympathetic fibers  Horner's syndrome (look for a smaller
pupil on the side of the third nerve palsy)
 DO BRAIN MRI WITH GADOLINIUM
4- orbital lesions :
- usually produce other orbital signs, including optic neuropathy,
chemosis, conjunctival injection or chemosis, and proptosis.
 DO MRI ON THE ORBIT

16. 2- ISOLATED 3rd N. PALSY :
1- complete internal dysfunction (pupil-involved) and complete or incomplete
external dysfunction :
 Complete internal dysfunction (pupil-involved) third nerve palsy should be
assumed to be due to aneurysmal compression until proven otherwise.
 Evaluation for intracranial aneurysm :
* contrast-enhanced MRI with MR angiography (MRA)  sensitivity 95-98%
* computed tomographic angiography (CTA)
* Cerebral angiography remains the gold standard test but is invasive and
associated with
infrequent but significant risk
- The risk of standard catheter angiography also depends on institution-specific
factors as well as
on and patient age and medical comorbidity.
- The relative risk of an underlying aneurysm is assessed based in large part on the
degree of
external and internal third nerve dysfunction  See table

17.  Once aneurysm and other mass lesions have been excluded, an evaluation for
giant cell arteritis should be undertaken in older patients; and an LP should be
considered for persistent or progressing deficits when the cause remains unclear.

18. 2- Complete external dysfunction with normal internal function (pupil-
sparing complete third nerve palsy) :
- Complete external dysfunction is identified when there is impairment of the
majority of function of all the somatic branches of the oculomotor nerve and
ptosis is complete or almost complete; otherwise the external dysfunction is
incomplete (eg, divisional palsy).
- it`s most commonly caused by ischemic injury
- it`s never caused by aneurism
- Risk factors : HTN , DM , Old Age
 DO CT-BRAIN , if not revealing , DO MRI-BRAIN
- In patients without vascular risk factors whose deficits progress or do not
improve by 6 to 12 weeks of follow-up or in those with signs of aberrant
regeneration
 DO CONTRAST-ENHANCED BRAIN MRI AND MRA
- Older patients (>55 years) should be evaluated for signs or symptoms of giant cell
arteritis (headache, jaw or tongue claudication, polymyalgia rheumatica, visual
loss).
 DO ESR , CRP , TEMPORALARTERY BIOBSY, STEROID TTT.

19. - If a third nerve palsy persists in a patient with normal imaging studies
 DO LUMBAR PUNCTURE (LP) ,especially if historical or
examination features suggest an infectious, inflammatory, or neoplastic process
affecting the meninges.
3- incomplete external dysfunction with no pupil involvement (eg,
divisional palsy) and incomplete or complete external dysfunction
with partial internal dysfunction (relative pupil-sparing) :
- DO CONTRASR ENHANCED BRAIN MRI to exclude mass lesion
- CTA or MRA to exclude aneurism, if –ve DO CATHETER ANGIO
- If masses and aneurism have been excluded  look for giant cell
arteritis (DO ESR , C-RP, ATREIAL PIOBSY) & DO LP if
inflammation or infection are suspected

20. 4- Isolated third nerve palsy with signs of aberrant regeneration :
- Signs of aberrant regeneration are unlikely in ischemic lesions and
suggest the presence of a compressive lesion, including aneurysm .
 CONTRAST ENHANCED BRAIN MRI WITH MRA (or CTA)
is the procedure of choice for these patients.

21. HORNER SYNDROME

22. 1- definition :
- Horner's syndrome is a classic neurologic syndrome
whose signs include miosis, ptosis, and anhidrosis.
Also called oculosympathetic paresis,
- Horner's syndrome can be produced by a lesion
anywhere along the sympathetic pathway that
supplies the head, eye, and neck

23. 2- neuroanatomy :
* Horner's syndrome can result from a lesion anywhere along a three-
neuron sympathetic (adrenergic) pathway that originates in the
hypothalamus
* The first-order neuron
- descends caudally from the hypothalamus to the first synapse,
which is located in the cervical spinal cord levels C8-T2, also
called ( ciliospinal center of Budge (
* The second-order neuron
- travels from the sympathetic trunk, through the brachial plexus,
over the lung apex.
- It then ascends to the superior cervical ganglion, located near
the angle of the mandible and the bifurcation of the common
carotid artery.
* The third-order neuron
- then ascends within the adventitia of the internal carotid artery,
through the cavernous sinus, where it is in close relation to the
sixth cranial nerve
- The oculosympathetic pathway then joins the ophthalmic (V1)
division of the fifth cranial nerve (trigeminal nerve).
- In the orbit and the eye, the oculosympathetic fibers innervate
the iris dilator muscle as well as Müller's muscle, a small smooth
muscle in the eyelids responsible for a minor portion of the upper
lid elevation and lower lid retraction.

24. 3- Etiology :

25. * NB. :-
- The most common cause of 1st order neuron lesion is lateral medullary $
(wallenberg $). It consists of horner $ , ataxia, vertigo, dissociated
sensory loss.
- The most common cause of 2nd order neuron lesion is iatrogenic.
- lumbar epidural anaesthesia is the most common cause in obstetric .
- Acute horner $ with neck or facial pain is considered internal carotid
dissection until proved otherwise

27. * N.B. :-
- The most common cause is delivery-related trauma to the neck and
shoulder, damaging the sympathetic pathway. Associated injury to the
lower brachial plexus can produce weakness in the ipsilateral forearm
and hand (Klumpke's paralysis) .
- In the absence of a clear history of birth trauma, an acquired Horner's
syndrome in a child should prompt evaluation for a tumor, particularly
a paraspinal neuroblastoma, which is known to present with a
Horner's syndrome.
- DO MRI of the head, neck, chest, and abdomen
- MEASURE urinary catecholamines.

28. 4- CLINICAL FEATURES :
- The classic signs of a Horner's syndrome are ptosis, miosis, and anhidrosis
- Miosis :-
- The degree of anisocoria is more marked in the dark than in light.
- There is associated dilation lag, an asymmetry in pupillary redilation between the two eyes when the light source is moved
away from the eye , the horner`s pupil will redilate more slowly( by 15-20 sec. ) than normal pupil .
- The ptosis :-
- is minor (less than 2 mm)
- occurs as a result of paralysis of the Müller's muscle, which is innervated by the sympathetic pathway. The lower as well
as the upper lid is affected, producing the so-called "upside-down ptosis." This further narrows the palpebral fissure.
- Anhidrosis:-
- is present in central or preganglionic (first or second-order) lesions .
- The sympathetic fibers responsible for facial sweating and vasodilation branch off at the superior cervical ganglion from
the remainder of the oculosympathetic pathway; thus, anhidrosis is not a feature of postganglionic or third-order lesions.
- This sign is frequently not apparent to patients or clinicians.
N.B :- In infants and children :-
- impaired facial flushing ( Harlequin sign ) is often more apparent than anhidrosis.
- Acute features of sympathetic disruption can also include ipsilateral conjunctival injection, nasal stuffiness, and
increased near point of accommodation.
N.B:- A congenital Horner's syndrome :-
- should be suspected when anisocoria is associated with heterochromia (unequal iris color, with the affected iris being
lighter).
- This occurs because formation of iris pigment in the first several months of age is under sympathetic control. This may
only be apparent if the natural color is relatively dark.

30. 5- localization :
=> Clinical localization :
1- brain stem : diplopa, vertigo, ataxia, lateralized
weakness
 DO MRI Brain.
2- spinal cord : bilateral or epsilateral weakness,
long tract signs, sensory levels, sphincteric.
 DO MRI Cervical.

31. 3- brachial plexus ingury at lung apex : arm pain
&/or hand weakness
 DO MRI OR CT- CHEST to evaluate lung
apex and paravertebral area.
4- cavernous sinus lesion :
Ipsilateral LR paresis In the absence of brain stem
signs d.t affection of 6th n.
 DO MRI on cavernous sinus.

32. 5- carotid artery dissection :
Suspected by isolated horner with neck or head
pain.
 DO Axial MRI of the neck and MRA
 Conventional angiography is the gold standard

34. => Pharmacological localization :
1- confirm diagnosis :
1- cocaine 5-10% test :
- prevent NE reuptake at sympath. N. synapses and causes pupillary dilation in
eyes with intact sympathetic innervation. Cocaine has no effect in eyes with
impaired sympathetic innervation, regardless of the lesion location.
- 2 cocaine drops in every eye  anisocoria ≥ 1mm is considered a positive
result.
- If the diagnosis of Horner's syndrome is clear clinically, then use of cocaine or
apraclonidine drops to confirm the diagnosis can be avoided, as their
administration will interfere with the hydroxyamphetamine test for
localization.

35. 2- apraclonidine 0.5% test :
- (α- adrenergic agonist )
- Weak α1(mediate pupilary dilatation) and strong α2
( downregulate NE ralease at NMJ)
- In a Horner's pupil, denervation supersensitivity to the alpha-1 receptor will cause
that pupil to dilate (usually by about 2 mm), while alpha-2 stimulation in the
normal eye will cause that pupil to constrict slightly (usually by <1 mm).
Reverse anisocoria
- Thus, one to two drops of 0.5 percent apraclonidine instilled in both eyes causes a
reversal of anisocoria in patients with Horner's syndrome.
- Comparison testing in small series of patients suggests that this test compares
favorably with cocaine in the diagnosis of Horner's syndrome

36. 2- for localization :
1- hydroxyamphetamine test :
- release stored NE from postganglionic adrenergic n. endings .
- differentiate 1st &2nd order lesions ( perganglionic ) from 3rd order
lesions ( postganglionic ) .
- There is no pharmacologic test to distinguish between first from
second-order lesions.
- Because cocaine may interfere with the uptake and efficacy of
hydroxyamphetamine drops, it is recommended that 24 to 72 hours
elapse between the two tests .
- One hour after instillation of 1 percent hydroxyamphetamine, a normal
pupil and a first or second-order Horner's pupil will dilate, whereas a
third-order Horner's pupil will not dilate as well as the normal pupil .
- a sensitivity of 93 to 96 % and a specificity of 84 % for detecting
postganglionic lesions .
- This test is not reliable in children in whom transynaptic degeneration
occurs .

37. 2- pholedrine test :
- It is hydroxyamphetamine derivative .
- It may be more available than hydroxyamphetamine in some
locations.
- The test using 1 percent pholedrine is performed in the same
manner as with hydroxyamphetamine .

39. THANK YOU ....,