Rule of 4 of the brainstem

Dr Henry Knipe and Rohit Sharma et al.

The rule of 4 of the brainstem was devised by Peter Gates, an Australian neurologist, in 2003 in order to simply explain the anatomy of the brainstem and basis of brainstem stroke syndromes to the non-neurologist and medical student 1-3. This article summarises Gates' four rules, associated important clinical deficits, important exceptions, and provides two examples of their clinical utility.

There are 4 cranial nerves from above the pons (including 2 from the midbrain), 4 from the pons, and 4 from the medulla oblongata

  • from above the pons:
    1. CN I (olfactory nerve): not from the midbrain, essentially a peripheral outpost of the central nervous system
    2. CN II (optic nerve): not from the midbrain, essentially a peripheral outpost of the central nervous system
    3. CN III (oculomotor nerve): from the midbrain, involvement leads classic 'down and out’ appearance with the eye resting in abduction, slight depression and intorsion due to paralysis of adduction, elevation and depression, pupil is often not involved (see oculomotor nerve palsy)
    4. CN IV (trochlear nerve): from the midbrain, involvement leads to the eye unable to look down when the eye is looking inferomedially (e.g. walking down stairs, reading, etc.), there is also head tilt away from affected eye
  • from the pons:
    1. CN V (trigeminal nerve): involvement leads to ipsilateral loss of pain and temperature on the face, also ipsilateral weakness of muscles of mastication
    2. CN VI (abducens nerve): involvement leads to ipsilateral weakness of abduction of the eye (see abducens nerve palsy)
    3. CN VII (facial nerve): involvement leads to ipsilateral facial weakness, loss of taste in the anterior two-thirds of the tongue, and hyperacusis
    4. CN VIII (vestibulocochlear nerve): involvement leads to ipsilateral deafness
      • importantly, the vestibular nucleus is located in the lateral medulla oblongata, involvement of which leads to vertigo, vomiting and nystagmus 4, although intractable vomiting can also occur due to damage to the area postrema in the dorsomedial aspect of the medulla oblongata 5
  • from the medulla oblongata:
    1. CN IX (glossopharyngeal nerve): involvement leads to ipsilateral loss of sensation of the tonsils, pharynx, middle ear, and posterior one-third of the tongue, there may be weakness in swallowing
    2. CN X (vagus nerve): involvement leads to ipsilateral palatal weakness and associated deviation of the uvula, loss of the gag reflex may also be present
    3. CN XI (accessory nerve): involvement leads to ipsilateral weakness in head rotation and elevation of shoulder (sternocleidomastoid and trapezius muscles respectively)
    4. CN XII (hypoglossal nerve): involvement leads to ipsilateral weakness of the tongue (deviates to side of lesion)

The 4 cranial nerve motor nuclei that are in the mid-line (actually paramedian) are those that divide equally into 12 except CN I and II:

  • mid-line (actually paramedian) 4 motor nuclei: those of CN III, IV, VI, and XII
  • lateral motor nuclei: those of CN V, VII, IX, X, and XI
  • no motor nuclei: CN I, II, VIII

There are 4 ‘mid-line’ (i.e. medial, but actually paramedian) structures beginning with ‘m’:

  1. motor pathway (corticospinal tract): involvement leads to contralateral loss of power of the limbs
  2. medial lemniscus (extension of dorsal columns): involvement leads to contralateral loss of vibration and proprioception of the limbs 
    • importantly, in the midbrain the medial lemniscus is located more lateral than in the pons and comes together with the spinothalamic pathway 4
  3. medial longitudinal fasciculus: involvement leads to ipsilateral internuclear ophthalmoplegia 
    • importantly, does not extend down to the medulla oblongata in any clinical relevance 4
  4. motor nucleus: involvement leads to ipsilateral loss of the cranial nerve motor nucleus (III, IV, VI, or XII) that is affected depending on level of the brainstem (see first rule) 

There are 4 ‘side’ (i.e. lateral) structures beginning with ‘s’:

  1. spinocerebellar pathway (extension of the spinocerebellar tract): involvement leads to ipsilateral ataxia of the limbs
    • an important caveat to this is in the midbrain, where involvement of the red nucleus (a medial midbrain structure) can also cause ataxia (albeit contralateral) and choreoathetosis (compare medial midbrain stroke syndromes Benedikt syndrome or Claude syndrome that involve the red nucleus with Weber syndrome that does not) 4
  2. spinothalamic pathway (extension of the lateral spinothalamic tract): involvement leads to contralateral loss of pain and temperature affecting the limbs
  3. sensory nucleus of CN V: involvement leads to ipsilateral loss of pain and temperature on the face in the distribution of CN V
    • importantly, does not extend up into the midbrain, and thus lesions of the midbrain spinothalamic pathway will cause total contralateral loss of pain, temperature, vibration, and proprioception (due to the medial lemniscus fibres also being more lateral in the midbrain) 4
  4. sympathetic pathway: involvement leads to ipsilateral Horner syndrome

Although Gates' rules simplify the anatomy of the brainstem, they are still very useful when approaching brainstem stroke syndromes 1-3. Furthermore, these rules can also be applied to clinical features developed as a result other brainstem lesions, such as demyelination, external brainstem compressions (e.g. cerebellopontine angle masses), and brainstem tumours 1,-3.

Importantly, not all of the features as suggested by the rule of 4 of the brainstem may be present in every brainstem stroke syndrome, as evident in many midbrain stroke syndromes in particular (as seen in above exceptions), but often only some are needed to localise the lesion 4. Furthermore, if both medial and lateral brainstem signs are detected clinically, then lesions such as a basilar artery occlusion (for pontine and midbrain syndromes) or hemimedullary syndrome from proximal vertebral artery occlusion should be suspected 1-4.

Working backwards for the sake of demonstration, if a patient is considered, using Gates' rule of 4 of the brainstem, with a known left-sided medial medullary syndrome (Dejerine syndrome).

  1. only medial motor CN nuclei can be affected: CN III, IV, VI, XII all have their nuclei medially
  2. however, only those in the medulla oblongata can be affected in this syndrome: leaving only the motor nuclei of CN XII
  3. being a medial syndrome, three of the four 'm' structures are present in the medulla oblongata: the motor pathway (spinothalamic tract), medial lemniscus, and the aforementioned CN XII motor nucleus
  4. being a known medial syndrome, 's' structures are not relevant

Thus, a patient with left-sided Dejerine syndrome is likely to present with right-sided limb weakness, right-sided loss of limb vibration and proprioception, and left-sided tongue weakness and atrophy.

Working to make a diagnosis as in real-life, if a patient is considered, using Gates' rule of 4 of the brainstem, presenting with right-sided deafness, ataxia, Horner syndrome, paralysis of the face, loss of pain and temperature from the face, and left-sided loss of pain and temperature in the limbs.

  1. given that the nuclei of CN VII and CN VIII (accounting for right-sided deafness) are involved, this must be a right-sided pontine lesion; it is uncertain if the lesion is medial or lateral at this stage
  2. given that the motor nucleus of CN VII (accounting for the right-sided facial paralysis) is involved, and this number does not divide equally into 12, this must then also be a lateral lesion; although use of further rules may not be necessary at this stage it is a good exercise in understanding
  3. mid-line 'm' structures are not relevant as this is clearly a 'side' (i.e. lateral) lesion
  4. involvement of the 's' structures, namely the spinothalamic pathway (accounting for left-sided loss of pain and temperature in the limbs), spinocerebellar pathway (accounting for right-sided ataxia), descending sympathetic pathway (accounting for right-sided Horner syndrome), and the sensory nucleus of CN V (accounting for right-sided loss of pain and temperature from the face), provide further confirmation of localisation to the right lateral pons

Thus, this constellation of clinical features is consistent with a right-sided lateral pontine syndrome (Marie-Foix syndrome).

Share article

Article information

rID: 54269
Sections: Anatomy, Gamuts
Synonyms or Alternate Spellings:
  • Brainstem rule of 4's
  • Gates' rule of 4 of the brainstem
  • Gates' brainstem rule of 4's

Support Radiopaedia and see fewer ads

Cases and figures

  • Drag
    Figure 1: brainstem nuclei
    Drag here to reorder.
  • Drag
    Figure 2: brainstem nuclei
    Drag here to reorder.
  • Drag
    Figure 3: brainstem motor nuclei
    Drag here to reorder.
  • Drag
    Figure 4: brainstem sensory nuclei
    Drag here to reorder.
  • Drag
    Figure 5: brainstem vascular territories
    Drag here to reorder.
  • Updating… Please wait.
    Loadinganimation

    Alert accept

    Error Unable to process the form. Check for errors and try again.

    Alert accept Thank you for updating your details.