Supranuclear Disorders: INO, 1&1/2, Parinaud's, PSP, CPEO

Question 1

Describe an intranuclear ophthalmoplegia?

Answer 1

• INO is a lesion of Medial Longitudinal Fasciculus (MLF) – bundle of nerve fibres that connects 3rd nerve nucleus for medial rectus muscle
  o It results in a palsy of Medial Rectus muscle
• MLF is the connecting bundle between opposite eyes lateral rectus & ipsilateral eyes medial rectus
  o PPRF – paramedian pontine reticular formation (horizontal gaze centre)
   Responsible for moving eyes Left & Right
• With dissociated gaze evoked nystagmus of abducting eye (Ataxic Nystagmus)
  o This eye is getting the info to move out but the adducting eye does not know to move to left as it didn’t get the message as MLF has a lesion there (as if it has been cut)

Question 2

Describe how the eyes are sitting in INO?

Answer 2

Exo in PP – not adducting
Exophoria – bigger at near than distance
May not have diplopia in PP – dip appears on side that they cannot adduct
Loss of adduction in one eye but can be bilateral
Ataxic nystagmus – one eye – brain keeps sending message/innervation to MR (will not work) so LR gets so much innervation -> nystagmus
If one MLF affected -> lesions are tiny & diffuse like MS or tiny microvascular event like stroke
FEF – frontal eye field

Question 3

What is the key differentiating factor for INO?

Answer 3

Convergence is a higher centre so should be intact –> key differentiating factor for INO
Characterised by loss of adduction
Convergence will likely NOT be affected

Question 4

If the px presents with INO what is likely cause if they are <50 and >50?

Answer 4

<50 – thinking MS
>50 – thinking vascular

Question 5

Describe the pathway involved in INO?

Answer 5

• To look to L – the right frontal eye field sends a signal to L PPRF
• The L PPRF innervates the L VI (abducens) nucleus, which controls L LR & cause LE to abduct (gaze left)
• Also the L VIN nucleus innervates the R IIIN (oculomotor) nucleus, which controls R MR muscle
  o Causing RE to adduct (gaze left)
  If lesion in L MLF then will be unable to move to R – opposite movement
• MLF is tract containing nerve fibres connecting R LR & L MR and L LR & R MR - VIN nucleus to contralateral IIIN nucleus
• In INO there is damage to MLF giving a deficit in adduction
• Convergence is usually still intact
  If do not have convergence then is likely to be a slightly higher lesion
  If still have convergence intact then the lesion is going to be lower down on the MLF

Question 6

What are the two types of INO?

Answer 6

Unilateral
Bilateral - more often

Question 7

What is the aetiology of INO?

Answer 7

• Multiple sclerosis – most commonly
  o Affects young pxs (20-50)
  o More concerned about MS if it is bilateral INO
  o DO NOT TELL THEM THEY HAVE MS!!!
   Refer immediately to ophthalmology/neurology
• Stroke – basilar artery occlusion
• Tumour rarely causes INO
  o Tumours tend to be bigger and cause other things too – not just INO
  If have bigger, more extensive lesion of MLF & within the brainstem then can affect other centres can result in a skew deviation (an acquired vertical misalignment of eyes not due to any single muscle or ocular motor nerve

Question 8

What are the presenting signs of INO?

Answer 8

• Exophoria/tropia in primary position
  o If it is a tropia then px will have diplopia – px will tell you they have double vision when reading
  o Any EXO deviation the px has will be greater at near than at distance
• This will increase on attempted adduction
• Impaired/slowed saccades are useful when differentiating a unilateral INO from an asymmetric bilateral INO
  o One eye cannot move past midline & other eye is perhaps able to adduct a little more
  o When things are bilateral, they do not tend to be equally affected – asymmetrically affected –> one eye more affected than other
• Ataxic nystagmus on lateral gaze
  o Eye appears to ‘bob’ – nystagmus only present in one eye so not a ‘true’ nystagmus thus ataxic nystagmus

Question 9

What is the differential diagnosis of INO?

Answer 9

• Myasthenia Gravis
  o Look for fatigue, variability, ptosis, Cogan’s lid twitch, involvement of vertical muscles
• Medial Wall (Blow-out Fracture (BO#))
  o Hx of trauma, enophthalmos, mechanical restriction of abduction
• Duane’s Retraction Syndrome
  o Much more common than INO
  o Looking for restriction of abduction & adduction, characteristic palpebral fissure changes
   May get globe retraction on attempted adduction
   Infranuclear Medial Rectus Palsy (Partial IIIrd Nerve Palsy) – Very Rare to get on its own – inferior division of 3rd nerve does not only supply MR, it also supplies IR, IO & pupil

Question 10

What are the main things to remember in an INO?

Answer 10

• Ipsilateral MR palsy – MR palsy in one eye
  o RMR palsy – then R INO – lesion of R MLF
• Saccades more affected than slow smooth pursuit
• Convergence may be intact – depends on site of lesion
• Ataxic nystagmus
• Skew deviation (because of where lesion is) – ipsilateral hypertropia
• Bilateral (both eyes) has gaze evoked vertical nystagmus & impaired vertical smooth pursuit
  o WEBINO – Wall-eyed Bilateral Internuclear Ophthalmoplegia
• Large-angled Exotropia if px had a previous exo deviation
• Common term in Neurology

Question 11

Describe the recovery of INO?

Answer 11

• Adduction can recover quite quickly in MS patients – especially if px is younger
• Ataxic nystagmus may take longer
• This can be a sign when examining a px w/ previous episodes of INO
  Looking for limitation of adduction in one eye with ataxic nystagmus of contralateral eye

Question 12

Describe one-and-a-half syndrome?

Answer 12

Unilateral INO and ipsilateral horizontal gaze palsy (rare but do happen, often had stroke)
Only movement eyes have is ataxic nystagmus for e.g. RE, can’t look left (INO in other eye, stops adducting)
* If have lesion in PPRF (horizontal gaze centre) and MLF – then unable to send any impulses to look in direction of gaze that is connected to PPRF
o Cannot look to R as don’t know to look to the R
 If cannot look to R then cannot abduct RE & therefore cannot adduct LE
 PPRF is what stops the px looking right, MLF is what stops one eye looking in adducted position
 Only movement px has in one-and-a-half is ataxic nystagmus of only eye that can actually abduct
If saw this then would refer immediately to HES

Question 13

Describe the aetiology of one-and-a-half syndrome?

Answer 13

• Extensive (big & v serious) lesion of caudal (lower) lesion of Pons
• Affecting horizontal gaze centre & adjacent MLF
• Bilateral MR Palsy & One Lateral Rectus Palsy (Gaze palsy + INO)
  o Only movement still possible is LR of opposite eye
• MS, Stroke, Tumour (most likely  least likely)

Question 14

Describe the features of one-and-a-half syndrome?

Answer 14

• Unilateral INO
• Ipsilateral (horizontal) gaze palsy
• Preserved (only movement is) abduction of contralateral eye
• Ataxic nystagmus
• Sometimes called Paralytic pontine exotropia
• Intact vertical motility (look up/down) & convergence (lesion is low in pons, lower in MLF – convergence sits in higher supranuclear centre
• VOR (vestibulocular reflex – ocular reflex that allows you to move head & eyes move in opposite direction) usually intact
  o If move px’s head, their eyes will still move but can’t ask them to make the conscious movement, they don’t have the responding eye movement pattern to follow a target  will not make any quick saccadic movements as they are unable to carry out that task of moving horizontally

Question 15

What is Parinaud’s Syndrome?

Answer 15

Most important vertical gaze palsy – serious syndrome – loss of upgaze – px often has papilloedema

Question 16

What are other names for one-and-a-half syndrome?

Answer 16

• Dorsal Midbrain Syndrome – tells you location – sitting at back
• Posterior Commissure Syndrome – sitting near the Posterior Commissure region
• Sylvian Aqueduct Syndrome – it is beside the Sylvian Aqueduct
• Nystagmus Retractorius Syndrome – px will present with Nystagmus Retractorius (eyes bob in & roatate backwards & forwards)

Question 17

What are the clinical features of one-and-a-half syndrome?

Answer 17

• Loss of upward saccadic movement with normal vertical pursuit
  o They will be able to follow the light target slowly – they have smooth pursuit normally unless huge lesion
• Convergence Retraction “Nystagmus” (rhythmic movement (not nystagmus)) – best seen using Optokinetic Nystagmus (OKN) drum on downward rotation
  o There is a characteristic rhythmical convergence movement of both eyes with retraction of globe
  o Only found when test their saccades
  o Eyes converge, both retract – nystagmus part is because it is a rhythmic oscillation of the eyes
   Can’t make saccades upwards, only do smooth pursuits upwards
   Px tries to lookup but don’t know how as no vertical centres (horizontal centres are working)
• Light/near dissociation – usually dilated pupils that react only to accommodation and not to light  WILL NOT SEE THIS IN OTHER SYNDROMES
  o Bring light up from below so don’t induce accommodation
  o But when ask them to follow budgy stick in towards nose – will get pupillary miosis
   Accommodation intact since different part to pupils
• Collier’s sign – bilateral upper eyelid retraction, sometimes with lid lag (lag of eyelids coming down when eyes go down)
• Papilloedema – children more likely to have hydrocephalus (swelling in brain) but can be present in adults too – children are not likely to tell you about the severe headache they will be experiencing  TAKE OCT to really examine the disc for swelling
  o Check their colour vision to check for swelling
• Convergence Insufficiency
• Accommodative Insufficiency
• Skew Deviation
• In extensive/progressive lesions you may also see:
  o IIIrd, IVth & VIth nerve palses
  o INO
   Look for all of these eye movement patterns

Question 18

Describe what happens if px has a pineal mass and it compresses (Parinaud’s Syndrome)?

Answer 18

• Pineal mass will compress
• Superior colliculi restricting upward saccades  anything sitting near superior colliculus will restrict up-gaze saccades
• Edinger-Westphal Nucleus (Rostral portion of Oculomotor Nerve) causing light near dissociation of pupils
  -Vertical gaze centre is quite ill-defined  not as classically cut as PPRF (for horizontal gaze)
  -If have swollen pineal gland  3rd ventricle will be much more engorged – so they start to develop increased intracranial pressure – mass growing here then affecting up-gaze centres
  -> this area is right beside superior colliculus – this then determines the eye movement pattern that px has

Question 19

Describe pinealoma (Parinaud’s Syndrome)?

Answer 19

• Quite an extensive lesion
• Sometimes pxs can have surgery to debulk this tumour & still have a Parinaud’s Syndrome following surgery  because in act of removing tumour mass – you are still damaging around that area  so px can be left with the Parinaud’s
• Tumour in pineal gland

Question 20

Describe Collier’s sign & sun setting (Parinaud’s syndrome)?

Answer 20

• This px has had a pinealoma
• They’ve had surgery (see sutures on top of head)
• Px still has Collier’s sign & sun setting (eyes are facing downwards)
• Huge lid retraction – upper eyelid quite retracted  top lid should be sitting closer to upper limbus
• Baby is looking down

Question 21

What is the management of Parinaud’s Syndrome?

Answer 21

Medical emergencies – you want them admitted that day – worried that they have a tumour/mass near their pineal gland

Question 22

Describe Progressive Supranuclear Palsy (PSP)?

Answer 22

Very important vertical gaze palsy – loss of downgaze  Fatal within 10 years
* Nasty, degenerative problem – rare
* Degeneration of the Brainstem Reticular Formation – difficulty w/ vertical gaze
* Is a disease of later life
* Also known as Steele-Richardson Syndrome
* The vertical gaze palsy differentiates the condition from other Parkinsonian disorders
o The vertical gaze palsy in this condition is quite unique
* Tremor, falls (mainly backwards)  need someone there with them all time
These pxs often present in practice looking for new glasses as they don’t know what is happening

Question 23

What are the ophthalmic signs of Progressive Supranuclear Palsy (PSP)?

Answer 23

• Impaired/slowing of Vertical saccades – often one of 1st signs
  o They do not have downward saccades
• Usually affecting downgaze initially – affects downgaze saccades
  o Therefore, different to Parinaud’s where lose up-gaze saccades
• Then complete loss of vertical saccades – once disease progresses
• Late stages may have Horizontal gaze disorders
  o With complete Ophthalmoplegia (unable to move eyes at all)
   Brain no longer able to control EOMs – unable to make eye movements
• Frequent square-wave jerks have been noted/saccadic intrusions
  o Px will be looking at object & saccadic intrusion will happen where eyes will make a sudden involuntary saccadic movement – there is then the difficulty where px cannot stop this happening (they often struggle to describe this)
  o When px should follow smooth pursuits but make these saccades
• Difficulty in voluntary opening the eyelids (Apraxia of lid opening) – when disease becomes much more progressive

Question 24

What are the neurological signs of Progressive Supranuclear Palsy (PSP)?

Answer 24

• History of early falls – so then think there is something wrong with their glasses
  o Especially backwards
  o Looks like Parkinson on walking
• Dysphagia with choking – pxs may then struggle to speak
• Symmetrical akinetic rigidity – where they are rigid & unable to move freely
• Absence of tremor
• Frontal Lobe Deficits – affects personality
  o Px may have been gregarious/outgoing – they are falling now/losing confidence, no longer able to speak clearly, may be choking on food
  o Px may become v angry, dramatic change in personality – personality disorder
• Pxs complain of difficulty seeing food on their plate – if they cannot look down
• Trouble walking downstairs – can be an early sign
• Combination of vertical gaze palsy (can’t make the quick movement to see next step when walking downstairs) and axial rigidity limiting neck movement
• Sadly, dementia and death usually occur approx. 10yrs after onset
  o Fatal

Question 25

Describe chronic progressive external ophthalmoplegia (CPEO)?

Answer 25

• Myogenic condition – NOT QUITE SUPRANUCLEAR
  o Px ends up with having an inability to move eyes completely
• Mitochondrial disorder
• Associated w/ Kearns Sayre Syndrome

Question 26

What are the clinical features of chronic progressive external ophthalmoplegia (CPEO)?

Answer 26

• Progressive symmetrical loss of motility
• Usually up-gaze is 1st to be affected
  o Ptosis & orbicularis weakness will also be affected
• Normal pupils & accommodation
  o Takes it away from supranuclear
• Diplopia is not usually complained of as this is a symmetrical problem & v slowly progressive
  o This is NOT a gaze palsy
• Final stage: have virtually no eye movements w/ +ve FDT (Force Duction Test – eye is physically moved) due to secondary fibrosis (this is why unable to move eye)

Question 27

Describe Kearns Sayre Syndrome?

Answer 27

• In a child who has difficulty with eye movements: ptosis, really extreme inability to look L & R
  o MUST LOOK FOR THIS CONDITION
• CPEO (in childhood)
• Fine pigmentary retinopathy
• Heart conduction block

Question 28

What is the differential diagnosis of CPEO?

Answer 28

• Myasthenia Gravis
• Graves’ Thyroid Eye Disease
• Supranuclear Gaze Palsy
• Multiple Nerve Palsies

Question 29

What is the management of CPEO?

Answer 29

• Fundoscopy – looking for pigmentary retinopathy
  o Must be sent for ECG immediately
• ECG
• Orthoptic assessment to include UFOF (uniocular field of fixation)
• Ptosis Props/Fresnels
• These pxs are v difficult to manage because it is a progressive condition that does not get better
  o Management may change depending on px – just aiming for them to be symptom free as much as possible