• Ptosis (levator palpebrae dysfunction)
• Affected eye deviated to a “down and out position” (unopposed lateral rectus and superior oblique)
• Diplopia
  • Patients don’t usually complain of diplopia due to ptosis but worst when looking up and out
• Fixed, dilated pupil (parasympathetic nerve fibres from ciliary ganglion affected)

• IIIrd nerve palsy
  • Down and out eye + fixed dilated pupil
• Horner’s syndrome
  • Ptosis + anhidrosis + miosis
• Myaesthenia Gravis
  • Bilateral facial weakness + proximal weakness with fatiguability + weak voice
• Congenital

• Myaesthenia Gravis
• Myotonic dystrophy
  • Frontotemporal balding + cataracts + wasting of facial/temporalis + small muscles of hand + distal weakness + depressed deep tendon reflexes
• Bilateral Horner’s syndrome
• Neurosyphilis
• Congenital

• “Medical”: pupil sparing (and painless)
• “Surgical”: pupil fixed and dilated
• Pathology
  • Parasympathetic fibres are situated on the periphery of the 3rd nerve trunk and so are the first to be affected by compression resulting in a fixed and dilated pupil.
  • The classic cause of a “surgical” 3rd nerve palsy is a posterior communicating artery aneurysm. The vaso vasorum which supplies the 3rd nerve starts from the centre and supplies out radially.
  • In “medical” 3rd nerve palsies the centre of the 3rd nerve is affected first leaving the parasympathetic fibres and therefore pupillary constriction intact until the end.

Pupil sparing in a third nerve palsy

Difference between a medical vs surgical 3rd nerve palsy

• Compression from a posterior communicating artery aneurysm
• Vascular occlusion (atheroma/diabetes)
• Midbrain infarct / tumour
• Temporal lobe coning

• Disruption of the sympathetic nervous supply to the face resulting in:
  • Ptosis: unilateral partial drooping of eyelid
  • Miosis: unilaterally constricted pupil
  • Anhidrosis: unilateral loss of sweating
  • Normal light and accommodation reflexes/eye movements

Click here for the clinical signs of Horner’s syndrome

• Pathology in Horner’s syndrome
  • In Horner’s syndrome there is only partial ptosis since control of the upper eyelid is controlled by two sets of nerves: the IIIrd nerve supplies the levator palpebrae superioris and sympathetic fibres supply the Muller muscle.
  • In Horner’s syndrome, despite the weakness owing to a dysfunctional Muller muscle, the IIIrd nerve is still intact meaning the ptosis is not complete. Interestingly, voluntary upward gaze overcomes the partial ptosis.
  • IIIrd nerve palsies and Myaesthenia gravis are two important differentials of Horner’s syndrome to exclude.
  • Presentation of Horner’s is dependent on the site of the lesion due to the anatomy of the sympathetic supply to the face. Sympathetic supply to the face is composed of the connection of three separate neurons:
  • First order neurone: Hypothalamus → Brainstem → Cervical Cord à T1 root ganglion
  • Second order neurone: T1 root ganglion → cervical sympathetic chain → superior cervical ganglion
  • Third order neurone: Superior cervical ganglion → Muller muscles + pupil + sweat glands
  • Central lesions affect the First order neurones and Peripheral lesions are those which affect the Second (pre-ganglionic) and Third (post ganglionic) order neurones. The ganglion is the superior cervical ganglion. Locating the lesion is dependent on identifying the pattern of anhidrosis:

• Third order neurone damage results in sweating being unaffected since the sympathetic fibres supplying the face branch off prior to the superior cervical ganglion.

• Can be classified based on site of lesion:
• First Order Neurone lesion:
  • Brainstem demyelination (MS)
  • Brainstem tumour
  • Brainstem infarct (lateral medullary infarct) /haemorrhage
  • Syringomyelia (cysts forming in spinal cord) – bilateral Horner’s
  • Arnold-Chiari malformation
  • Neck trauma
• Second Order Neurone lesion:
  • Apical lung tumour – classically Pancoast tumour
  • Apical TB
  • Cervical rib
  • Brachial plexus trauma
  • Iatrogenic: Central venous catherisation / Cardiothoracic + Neck surgery
  • Dissections + aneurysms of carotid and subclavian artery
  • Birth trauma
• Third Order Neurone lesion:
  • Herpes Zoster
  • Internal carotid artery dissection

• Mnemonic
  • SO₄ = Superior oblique is supplied by Trochlear nerve (4th)
  • LR6 = Lateral rectus is supplied by Abducens (6th)
• Presentation of 4^th nerve palsy:
  • A 4th nerve palsy results in the patient being unable to look down and in, towards their nose, making reading especially difficult.
  • On inspection of the patient the affected eye will be slightly raised compared to the unaffected eye.
  • Diplopia, experienced as images at an angle (angulated diplopia), is worst when looking down and in.
  • To counteract the diplopia patients are commonly seen raising the level of the affected eye by tilting their head away from the side of the lesion i.e. a patient with a right 4th nerve palsy will tilt their head away such that, when looking at the patient, their right ear is higher than their left ear.

Video on left Trochlear (4th) nerve palsy

Note when patient is asked to look to the right the left eye looks slightly upwards due to the unopposed action of the intact inferior oblique muscle

• Presentation of sixth nerve palsy
  • VI nerve palsy is can be a “false localising” sign.
  • Due to the long course of the 6th nerve it is easily affected, for example in patients with raised intracerebral pressure.
  • Diplopia is experienced as parallel images and is greatest when looking towards the affected side.

Video on Abducens (6th) nerve palsy

• Lesion to the medial longitudinal fasciculus
• Medial longitudinal fasciculus (MLF) is a collection of neuronal fibres which connect the Oculomotor (III), Trochlear (IV), Abducens (VI) nuclei in the brainstem to allow conjugate eye movement.
• For example, the ipsilateral VIth nuclei (controlling the lateral rectus muscle) is connected, through the MLF, to the contralateral IIIrd nuclei (controlling medial rectus muscle) to allow coordinated movement of both eyes laterally (lateral gaze).

• Eyes do not move together – dissociative conjugate movements
• Impaired adduction of the ipsilateral eye
• Nystagmus in the abducting contralateral eye
• A patient with a MLF lesion when asked to look to the left will be able abduct their left eye but will have impaired adduction of their right eye as the connection between the left VIth nerve nucleus (left lateral rectus) and the right IIIrd nerve nucleus (medial rectus) is not functioning.
• The abducting eye (in this case the left) will also show signs of nystagmus. This is sign may or may not be present.
• Nystagmus occurs since the brain, noticing that gaze is divergent due to the impaired adduction of the right eye, tried to correct the gaze of the abducted left eye back toward the nose. This flicking between the left eye abducting and correcting results in a lateral nystagmus.
• Patient with an INO still have normal convergence as both 3rd nerve nuclei (medial rectus) are both intact.
• Importantly when the contralateral abducting eye is covered the adduction of ipsilateral eye is normal.

Video on Internuclear opthalmoplegia (INO)

• MS: cerebellar signs + afferent pupillary defect + optic atrophy + pyramidal + dorsal column signs)
• Brainstem infarcts/tumours (pontine glioma) /aneurysms
• Wernicke’s encephalopathy: signs of alcohol abuse/vitamin B12 deficiency
• SLE
• Overdose on phenytoin / TCAs / Barbituates

• Nystagmus is the characteristic flicking/shaking of the eyes caused by a slow drift in one direction with a fast correction in the opposite direction.
• Usually the nystagmus is described in the direction of the fast phase
• Nystagmus can be physiological (oculokinetic nystagmus i.e. when looking out the window of a fast train) or caused by pathology in the cerebellar or vestibular systems.

• D = Dysdiadokinesis (impaired rapid alternating movements) + dysmetria (past-pointing when at full stretch)
• A = Ataxia
• N = Nystagmus (fast component is towards the side of the lesion)
• I = Intention tremor (gets worse as finger approaches the target)
• S = Slurred speech
• H = Hypotonia