Brainstem Rules of 4

 

In 2005, Peter Gates published a superb paper titled:

‘The rule of 4 of the brainstem: a simplified method for understanding brainstem anatomy and brainstem vascular syndromes for the non-neurologist’.

Gates described a simplified method for answering the question ‘Where is the lesion?’ using only the parts of the brainstem that we actually examine during a clinical examination to understand brainstem vascular syndromes.

Firstly, a quick review of the blood supply of the brainstem. Simply put the blood supply comes from:

1. paramedian branches
2. long circumferential branches (SAP)

• superior cerebellar artery (SCA)
• anterior inferior cerebellar artery (AICA)
• posterior inferior cerebellar artery (PICA)

And occlusion of these two groups of vessels results in two distinct types of brainstem syndrome:

1. medial (or paramedian) brainstem syndromes ( due to para-median branch occlusion)
2. lateral brainstem syndromes ( due to occlusion of the circumferential branches, also occasionally seen in unilateral vertebral occlusion)

And now the rules. If you can remember these rules the  diagnosis of brainstem vascular syndromes becomes a pitifully simple exercise (?!) - here’s how it works:

In the rule of 4 there are 4 rules

1. There are 4 structures in the ‘midline‘ beginning with M
2. There are 4 structures to the ‘side‘ (lateral) beginning with S
3. There are 4 cranial nerves in the medulla, 4 in the pons and 4 above the pons (2 in the midbrain)
4. The 4 motor nuclei that are in the midline are those that divide equally into 12 except for 1 and 2, that is 3, 4, 6 and 12
   (5, 7, 9 and 11 are in the lateral brainstem)

The 4 medial structures and the associated deficits are:

1. Motor pathway (or corticospinal tract):
   contralateral weakness of the arm and leg
2. Medial Lemniscus:
   contralateral loss of vibration and proprioception in the arm and leg
3. Medial longitudinal fasciculus:
   ipsilateral inter-nuclear ophthalmoplegia
   (failure of adduction of the ipsilateral eye towards the nose and nystagmus in the opposite eye as it looks laterally)
4. Motor nucleus and nerve:
   ipsilateral loss of the cranial nerve that is affected (3, 4, 6 or 12)

The 4 ’side’ (lateral) structures and the associated deficits are:

1. Spinocerebellar pathway:
   ipsilateral ataxia of the arm and leg
2. Spinothalamic pathway:
   contralateral alteration of pain and temperature affecting the arm, leg and rarely the trunk
3. Sensory nucleus of the 5th cranial nerve:
   ipsilateral alteration of pain and temperature on the face in the distribution of the 5th cranial nerve
   (this nucleus is a long vertical structure that extends in the lateral aspect of the pons down into the medulla)
4. Sympathetic pathway:
   ipsilateral Homer’s syndrome, that is partial ptosis and a small pupil (miosis)

According to Gates:

These pathways pass through the entire length of the brainstem and can be likened to ‘meridians of longitude‘ whereas the various cranial nerves can be regarded as ‘parallels of latitude‘. If you establish where the meridians of longitude and parallels of latitude intersect then you have established the site of the lesion.

The 4 cranial nerves in the medulla are CN9-12:

1. Glossopharyngeal (CN9):
   ipsilateral loss of pharyngeal sensation
2. Vagus (CN10):
   ipsilateral palatal weakness
3. Spinal accessory (CN11):
   ipsilateral weakness of the trapezius and stemocleidomastoid muscles
4. Hypoglossal (CN12):
   ipsilateral weakness of the tongue

The 12th cranial nerve is the motor nerve in the midline of the medulla. Although the 9th, 10th and 11th cranial nerves have motor components, they do not divide evenly into 12 (using our rule) and are thus not the medial motor nerves.

The 4 cranial nerves in the pons are CN5-8:

1. Trigeminal (CN5):
   ipsilateral alteration of pain, temperature and light touch on the face back as far as the anterior two-thirds of the scalp and sparing the angle of the jaw.
2. Abducent (CN6):
   ipsilateral weakness of abduction (lateral movement) of the eye (lateral rectus).
3. Facial (CN7):
   ipsilateral facial weakness.
4. Auditory (CN8):
   ipsilateral deafness.

The 6th cranial nerve is the motor nerve in the medial pons.
The 7th is a motor nerve but it also carries pathways of taste, and using the rule of 4 it does not divide equally in to 12 and thus it is not a motor nerve that is in the midline.
The vestibular portion of the 8th nerve is not included in order to keep the concept simple and to avoid confusion. Nausea and vomiting and vertigo are often more common with involvement of the vestibular connections in the lateral medulla.

The 4 cranial nerves above the pons are CN1-4:

1. Olfactory (CN1):
   not in midbrain.
2. Optic (CN2):
   not in midbrain.
3. Oculomotor (CN3):
   impaired adduction, supradduction and infradduction of the ipsilateral eye with or without a dilated pupil.
   The eye is turned out and slightly down.
4. Trochlear (CN4):
   eye unable to look down when the eye is looking in towards the nose (superior oblique).

The 3rd and 4th cranial nerves are the motor nerves in the midbrain.

Thus a medial brainstem syndrome will consist of the 4 M’s and the relevant motor cranial nerves, and a lateral brainstem syndrome will consist of the 4 S’s and either
the 9-11th cranial nerve if the lesion is in the medulla, or the 5th, 7th and 8th cranial nerve if the lesion is in the pons.

Handy tip:
If there are signs of both a lateral and a medial (paramedian) brainstem syndrome, then one needs to consider a basilar artery problem, possibly an occlusion.

I’ll let you mull over these rules until the next ‘brainstem’ post, where you’ll be able to test drive ‘Gates’ Brainstem Rules of 4′ on some clinical scenarios.

Scenario 1

• You are examining a patient with sudden onset left-sided weakness. These are your clinical examination findings:
  weakness of the left upper and lower limbs, with sparing of the face.
  tongue deviation to the right, with no ophthalmoplegia.
  loss of vibration and proprioception in the left upper and lower limbs.
• 
• Where is the lesion?
  weakness of the left upper and lower limbs, with sparing of the face:
  motor (corticospinal pathway) localises the lesion to the contralateral medial brainstem
  (sparing of the face (CN7) means the lesion must be below the upper pons)
  tongue deviation to the right, with no ophthalmoplegia:
  tongue deviation indicates CN12 involvement, localising the lesion to the ipsilateral medulla
  (sparing of CN3 and CN6 means the midbrain and pons are not involved)
  loss of vibration and proprioception in the left upper and lower limbs:
  confirms localisation of the lesion to the contralateral medial brainstem
• Site of the lesion: right medial medulla. Sometimes, due to the peculiar pattern of blood supply to the medulla, bilateral infarction may occur.

Scenario 2

• You are examining a patient with sudden onset right-sided weakness. These are your clinical examination findings:
  weakness of the right face, upper and lower limbs.
  the left eye is turned “down and out” and the pupil is dilated.
• Where is the lesion?
  weakness of the right face, upper and lower limbs:
  motor (corticospinal pathway) localises the lesion to the contralateral medial brainstem
  (involvement of the face means the lesion must be at or above the upper pons)
  the left eye is turned “down and out” and the pupil is dilated:
  CN3 involvement, localising the lesion to the ipsilateral midbrain
  (sparing of CN6 and CN12 means the pons and medulla are not involved)
• Site of the lesion: left medial midbrain. A CN3 palsy (from damage to the CN3 nerve fascicle) and contralateral hemiplegia is known as Weber’s syndrome (”basal” infarction)  - which can be difficult to distinguish from ‘coning’ if you don’t have a CT scanner available.

Scenario 3

• You are examining a patient with vertigo, vomiting, and nystagmus. These are your clinical examination findings:
  left-sided limb ataxia.
  left-sided alteration of pain and temperature on the face.
  left-sided ipsilateral Homer’s syndrome.
  right-sided alteration of pain and temperature affecting the arm and leg.
  dysarthria and decreased gag reflex on the left, with the palate pulling up on the right-side.
• 
• Where is the lesion?
  left-sided limb ataxia:
  spinocerebellar pathway localises the lesion to the ipsilateral lateral brainstem.
  left-sided alteration of pain and temperature on the face:
  Sensory nucleus of the 5th cranial nerve localises the lesion to the ipsilateral lateral brainstem.
  left-sided ipsilateral Homer’s syndrome:
  Sympathetic pathway localises the lesion to the ipsilateral lateral brainstem.
  right-sided alteration of pain and temperature affecting the arm and leg:
  Spinothalamic pathway localises the lesion to the contralateral lateral brainstem.
  dysarthria and decreased gag reflex on the left, with the palate pulling up on the right-side:
  localises the lesion to the medulla affecting the ipsilateral  CN9 and 10.
• Site of the lesion: left lateral medulla. Also known as Wallenberg’s syndrome, caused by a left vertebral or left posterior inferior cerebellar artery occlusion (blood supply is variable to this region).

Scenario 4

• You are examining a patient with right-sided deafness, that was preceded by tinnitus. These are your clinical examination findings:
  right-sided limb ataxia (predominantly affecting the right upper limb).
  right-sided facial numbness with loss of the corneal reflex.
  right-sided hemi-facial spasms.
• Where is the lesion?
  right-sided limb ataxia (predominantly affecting the right upper limb):
  spinocerebellar pathway localises the lesion to the ipsilateral lateral brainstem.
  right-sided facial numbness with loss of the corneal reflex:
  Sensory nucleus of the 5th cranial nerve localises the lesion to the ipsilateral lateral brainstem.
  right-sided hemi-facial spasms:
  the lesion involves the pons affecting the ipsilateral CN7.
• Site of the lesion: The findings indicate a lesion affecting the right lateral pons with evidence of spinocerebellar involvement. In this case the lesion was not vascular in origin but in fact an example of a cerebropontine angle lesion - an acoustic neuroma (or schwannoma). This demonstrates the the broader utility of Gates’ Brainstem Rules of 4.

Scenario 5

• You are examining a patient with sudden onset right-sided weakness. These are your clinical examination findings:
  weakness of the right face, upper and lower limbs.
  failure of abduction of the left eye.
  loss of vibration and proprioception in the right upper and lower limbs.
• Where is the lesion?
  weakness of the right face, upper and lower limbs:
  motor (corticospinal pathway) localises the lesion to the contralateral medial brainstem
  (involvement of the face means the lesion must be at or above the upper pons)
  failure of abduction of the left eye:
  indicates CN6 involvement, localising the lesion to the ipsilateral pons.
  (sparing of CN3 and CN12 means the midbrain and medulla are not involved)
  loss of vibration and proprioception in the right upper and lower limbs:
  confirms localisation of the lesion to the contralateral medial brainstem
• Site of the lesion: left medial pons. Interestingly, the facial nerve runs a strange course - it loops around medial to the CN6 nucleus from its own laterally situated CN7 nucleus. Thus a CN7 palsy tends to coexist with a CN6 lesion despite the CN7 nucleus being in the lateral pons.

Scenario 6

• You are examining a patient with sudden onset intermittent double vision (diplopia). These are your clinical examination findings:
  failure of adduction past the midline (movement towards the nose) of the left eye and leading eye (right) nystagmus on looking laterally to the right. Normal eye movements on looking to the left.
  The patient is hypertensive. There is no hemiparesis and further examination is unremarkable.
• Where is the lesion?
  This finding  suggests a unilateral left-sided internuclear ophthalmoplegia, which localises the lesion to the ipsilateral medial longitudinal fasciculus (MLF). The MLF connects CN3 in the midbrain and the contralateral CN6 in the pons.
  The MLF is not usually affected when there is hemiparesis as it lies further back in the brainstem relative to the motor (corticospinal) pathway.
  Unilateral internuclear ophthalmoplegia can result from a lacunar infarct.
  (Always remember the possibility of multiple sclerosis)
• Site of the lesion: left medial longitudinal fasciculus (connects CN3 in the midbrain and contralateral CN6 in the pons).

Scenario 7

• You are examining a patient with a right-sided Horner’s syndrome. These are your clinical examination findings:
  right-sided Horner’s syndrome.
  right-sided limb ataxia.
  left-sided total loss of sensation.
• Where is the lesion?
  right-sided Horner’s syndrome:
  sympathetic pathway localises the lesion to the ipsilateral lateral brainstem.
  right-sided limb ataxia:
  spinocerebellar pathway localises the lesion to the ipsilateral lateral brainstem.
  left-sided total loss of sensation:
  Spinothalamic pathway localises the lesion to the contralateral lateral brainstem (in the midbrain the medial lemniscal pathway is actually situated more laterally, ventral to the spinothalamic pathway - ie. the two pathways come together… an exception to the Rule of 4!).
• Site of the lesion: Right dorsolateral midbrain. An extensive lesion that also involves CN3 is known by the delightful name of Nothnagel’s syndrome.

Scenario 8

• You are examining a patient with a ‘down and out’ right eye with pupillary dilatation. These are your clinical examination findings:
  right-sided impaired adduction, supradduction and infradduction of the ipsilateral eye with a dilated pupil.
  left-sided limb ataxia.
• Where is the lesion?
  right-sided impaired adduction, supradduction and infradduction of the ipsilateral eye with a dilated pupil:
  CN3 lesion localises the lesion to the ipsilateral medial midbrain.
  left-sided limb ataxia:
  usually this indicates ipsilateral spinocerebellar pathway involvment (a lateral structure). However, in this case we know that the midbrain is affected (CN3 palsy) and the red nucleus lies in the medial midbrain just lateral to the CN3 nerve fascicle. Damage to the red nucleus interrupts the ‘dentatorubrothalamic tract’ from the opposite cerebellar hemisphere causing cerebellar signs in the limbs opposite to the CN3 lesion.
• Site of the lesion: Right medial midbrain. The clinical manifestations of this lesion (affecting the CN3 nucleus or its fascicle as well as the red nucleus) is known as Benedikt’s syndrome.

 

Taken from: Life in the Fast Lane