25th June 2023

Cranial Nerve Neuroanatomy

Rule of Four

The cranial nerves consist of twelve paired nerves that can be characterised as follows:

They can be structurally abstracted as part of the Rule of 4:

• 4 cranial nerves are situated above the pons: CN 1 and 2 in cerebrum, CN 3 and 4 in midbrain
• 4 cranial nerves are situated within the pons: CN 5, 6, 7, and 8
• 4 cranial nerves are situated below the pons: CN 9, 10, 11, and 12
• 4 motor cranial nerve nuclei are in the midline: CN 3, 4, 6 and 12, which are associated with three other important structures – the corticospinal tract (motor pathway), medial lemniscus (vibration and proprioception), and medial longitudinal fasciculus.
• 4 cranial nerve nuclei are in the lateral brainstem: CN 5, 7, 9 and 10, which are associated with three other important structures – the spinocerebellar pathway, spinothalamic pathway, and sympathetic pathway.
• 4 cranial nerves are closely related at the cerebellopontine angle – CN 5, 6, 7, 8, and the cerebellum. Tumours at that area, e.g. a vestibular schwannoma, are likely to cause ipsilateral CN 5,6,7 and 8 palsies with ataxia.

Decussations and bilateral innervation

A cranial nerve (i.e. the axon to and from its lower motor neuron nuclei) does not decussate, i.e. cross over to the opposite side, with the exceptions of the trochlear nerve (CN 4), and the medial fibres of the optic nerve (CN 2).

CN 2, 4, 7, and 12 cranial nerve nuclei receive bilateral innervation from upper motor neuron cortical inputs; therefore, cortical lesions can affect tracts to the cranial nuclei and subsequently result in an observed disorder of cranial nerve function, despite the lesion not affecting the cranial nerve directly.

Lower motor cranial nerve nuclei disorders will always result in an ipsilateral disorder except for CN 2 and CN 4, while lesions that affect upper motor cranial nuclei will result in bilateral or contralateral manifestations. The common examples of these will be discussed in the following sections.

Anatomical Relevance

In general, isolated disorders of the cranial nerve itself, i.e. lower motor neuron lesions of the cranial nerve, are less common than pathology affecting cortical/supranuclear pathways contributing to the relevant cranial nerves or pathology that will generally affect several nerves, e.g. generalised neuropathy. There are several common aetiologies that can affect any distribution of nerves and also affect supranuclear contributions to cranial nerves.

In general:

• Any physical impediment along the course of a cranial nerve can result in loss of function; this is commonly due to traumatic causes or neoplastic causes
• Neuroinflammatory conditions, e.g. multiple sclerosis, Lyme disease can affect any distribution of nerves and, while less common, can cause isolated cranial nerve palsies.
• Ischaemia and infarction; a macrovascular infarction, i.e. stroke, can cause supranuclear or lower motor nuclear manifestations.
  • As per the rule of 4, infarctions above the level of the involved cranial nerve nuclei would result in an upper motor neuron manifestation of cranial nerve dysfunction, while lesions at the level of the nuclei cause lower motor neuron manifestations.
  • For example, a pontine stroke due to posterior circulation infarction can cause an ipsilateral complete facial palsy (lesion at level of CN 7 nuclei ) with possible pseudobulbar palsy (above the level of CN 9, 10 and 12 nuclei), while a cortical anterior circulation infarction would cause a contralateral forehead sparing facial palsy (being above the level of CN 7 etc.)
• Microvascular changes, e.g. in diabetes mellitus, can cause ischaemia to any nerve, including cranial nerves.

False localising signs

A neurological sign is described as a false localising sign if it reflects dysfunction distant from the actual pathology. It commonly arises due to space-occupying lesions and diseases that cause raised intracranial pressure, including idiopathic intracranial hypertension. Extracranial false localising signs arise mainly due to spinal cord lesions.

Some anatomical considerations to consider are:

• Cranial nerve with the longest intracranial course is CN 4 – more vulnerable to head trauma
• Cranial nerve with the longest intradural course is CN 6 – most likely to be affected by raised intracranial pressure, vulnerable to stretching, classic example of false localising signs.
• CN 3 passes close to the tentorium and is vulnerable to uncal herniation/pressure effects at that level – vulnerable to false localisation

Not necessarily related to false localising signs but of interest :

• Cranial nerve with the longest intraosseous course is CN 7 – making it vulnerable to infection, trauma and congenital conditions with craniofacial craniosynostosis. Note its descent in the petrous part of the temporal bone which makes it vulnerable to facial fractures.
• Cranial nerve with longest extracranial course is CN 10 –vulnerable to traction and compression in the cervical area
• Cranial nerves in the cavernous sinus are CN 6, CN 3, CN 4, CN 5a – targets for cerebral venous sinus thrombosis.