Cranial nerves

What it normally does

• Three nerves move the eye and one of them does most of the work. The sixth (abducens) pulls the eye outward (lateral rectus). The fourth (trochlear) supplies the superior oblique, which intorts the eye and depresses it - and it depresses most powerfully when the eye is already adducted, which is why it is tested looking down and in, even though the muscle itself abducts rather than adducts. The third (oculomotor) does everything else - the other four eye muscles (superior, inferior and medial rectus, and inferior oblique), the lid lifter (levator palpebrae superioris), and the parasympathetic fibres that constrict the pupil and focus the lens. Those parasympathetic fibres run near the outer surface of the third nerve, fed by pial vessels on its surface; the fibres to muscle run in the core, fed by tiny vessels inside the nerve (vasa nervorum). The sixth nerve has a long and sharply angled intracranial course, draped over the petrous ridge of the temporal bone and tethered as it passes beneath the petroclinoid ligament.

  squeezing from outside - an aneurysm at the posterior communicating artery, or the temporal lobe herniating over the tentorium - takes out the pupil first, while a small-vessel infarct inside the nerve in a person with diabetes strangles the core and spares the pupil; a fourth nerve palsy leaves the eye sitting slightly high and extorted, with vertical double vision worst looking down and the head tilted away from the bad side; and a sixth nerve palsy can appear from raised pressure anywhere in the skull, pointing nowhere in particular.

• The seventh nerve (facial) is the motor nerve of the face, and it carries three passengers: a twig to stapedius, the muscle that damps the ossicles against loud sound; taste from the front two-thirds of the tongue (chorda tympani); and parasympathetic fibres to the tear gland and to the submandibular and sublingual salivary glands. It reaches the face through a narrow bony tunnel in the skull base (facial canal) with no room to swell. Above the nucleus, the cortex sends fibres to the forehead half from BOTH hemispheres, and to the lower-face half from the opposite hemisphere only.

  a lesion of the nerve itself weakens the whole half of the face and can add uncomfortably loud hearing, a dry eye and loss of taste, whereas a stroke in one hemisphere spares the forehead - one sign separates Bell palsy from a stroke at the bedside.

• Swallowing, speech and airway protection run on the lower nerves out of the medulla (the bulb). The ninth (glossopharyngeal) carries sensation from the back of the throat - the 'something is there' limb of the gag. The tenth (vagus) lifts the palate, drives the pharyngeal squeeze, and through the recurrent laryngeal nerve moves the vocal cords; it is also the efferent limb of the gag. The twelfth (hypoglossal) moves the tongue, each genioglossus pushing the tongue toward the opposite side. Like the forehead, the nucleus ambiguus (palate, pharynx, larynx) takes cortical input from both hemispheres; the hypoglossal nucleus is largely bilateral too, except for the part supplying genioglossus, which is driven mainly by the opposite hemisphere.

  one damaged nerve gives one specific sign - the uvula pulls away from the weak side, the tongue pokes toward it - while damage to the nuclei themselves (bulbar) or to both sets of descending cortical fibres (pseudobulbar) makes swallowing unsafe; and because that input is bilateral, one stroke rarely does that, two do. The genioglossus exception is why a single cortical stroke can still push the tongue away from the side of the lesion, but without the wasting and fasciculation of a nerve or nuclear lesion.

• Every cranial motor nerve ends the same way. The nerve terminal releases packets of acetylcholine into the gap, they bind nicotinic receptors on the muscle, the receptors open and the muscle fires; acetylcholinesterase in the gap destroys the transmitter within milliseconds. Normally far more receptors open than are needed to reach threshold - a safety margin. During sustained firing each impulse releases slightly less transmitter than the one before, and the small, fast, constantly working muscles of the eyelids, eyes and throat have the thinnest safety margin of all. The pupil is not part of this system: the sphincter pupillae is smooth muscle driven by muscarinic receptors.

  when receptors are lost the safety margin disappears and weakness appears with use - a lid that droops through the day, a voice that goes nasal as the sentence goes on - while the pupil stays normal, which is how fatigable ptosis is told apart from a third nerve palsy.

What goes wrong

• Third nerve palsy← from “Three nerves move the eye and one of them does…”

  The nerve stops holding the eye up and in and stops lifting the lid, so the two muscles it does not supply - lateral rectus and superior oblique - drag the eye down and out while the lid falls. Where the damage sits decides the pupil. Something pressing from outside (a posterior communicating artery aneurysm, or the medial temporal lobe squeezing over the tentorium as intracranial pressure rises) crushes the superficial parasympathetic fibres first, so the pupil dilates early and stops reacting. A microvascular infarct from diabetes or hypertension damages the core of the nerve and leaves the surface fibres working, so the pupil still reacts.

  Pupil involved means compression - image the vessels today. Pupil spared in someone with vascular risk factors is usually microvascular and recovers over about three months. Two caveats on the pupil-sparing rule: it is only reassuring when the external ophthalmoplegia is otherwise complete, and it does not apply to a young person with no vascular risk factors, to a partial palsy, or to one that progresses or fails to improve - image those. Type 2 diabetes runs at several times the rate in Aboriginal and Torres Strait Islander Australians and starts a decade or more younger, so microvascular palsies turn up younger too.

  You would find: Droopy lid, eye sitting down and out, double vision. Lift the lid and look at the pupil. A dilated unreactive pupil with a third nerve palsy is an aneurysm until CT angiography says otherwise, and pain does not settle the argument - the diabetic one hurts too. A drowsy patient with an enlarging pupil is herniation, not an eye problem.

• Bell palsy← from “The seventh nerve (facial) is the motor nerve …”

  The seventh nerve becomes inflamed and swells inside its bony canal - reactivation of herpes simplex in the geniculate ganglion is the best-supported hypothesis, though it is not proven - and bone does not give, so the nerve is compressed against it and stops conducting. Everything the nerve carries fails together: all the muscles of that half of the face, stapedius, taste at the front of the tongue, and tear production.

  Roughly 20 to 30 per 100 000 per year, and most recover fully. It is a diagnosis of exclusion: look in the ear (chronic suppurative otitis media and cholesteatoma cause facial palsy and are far more common in remote Aboriginal and Torres Strait Islander communities), check whether it is bilateral (Guillain-Barre, sarcoidosis, HIV, and in a returned traveller Lyme disease - which is not acquired in Australia), and check the other cranial nerves and the limbs. The eye is the emergency - it does not close and the cornea will ulcer.

  You would find: Onset over hours to about three days. One whole half of the face is weak - they cannot wrinkle the forehead or bury the eyelashes, and the eyeball rolls up as they try to shut the eye (Bell phenomenon). The mouth droops, food collects in that cheek, sound is uncomfortably loud on that side and taste is off. If the forehead still moves, it is not Bell palsy - look for a stroke. Vesicles in the ear canal or on the pinna make it Ramsay Hunt syndrome (varicella zoster), which recovers less well.

• Bulbar and pseudobulbar palsy← from “Swallowing, speech and airway protection run o…”

  Bulbar: the medullary nuclei or the nerves themselves are destroyed - motor neurone disease, brainstem stroke, Guillain-Barre - so the swallowing and speech muscles go floppy. Pseudobulbar: the nuclei are intact but both sets of descending cortical fibres are damaged (two strokes, multiple sclerosis, motor neurone disease), so the same muscles become stiff and slow and lose voluntary control while their reflexes stay brisk. Because the cortical input is bilateral, it takes damage on both sides to do this.

  Watch them drink a glass of water. A wet gurgly voice after the swallow and a delayed cough mean an unsafe swallow whatever the imaging says. The gag reflex is a poor test on its own - it is absent in a fair proportion of normal people and present in some who aspirate. Stroke is the commonest cause, and Aboriginal and Torres Strait Islander Australians have stroke at roughly twice the rate and considerably younger.

  You would find: Floppy version: wasted, fasciculating tongue that cannot be pushed out, nasal speech, fluid coming back down the nose, weak wet cough, reduced or absent gag. Stiff version: small tight tongue that will not move side to side, slow strangled speech, brisk jaw jerk, and crying or laughing the patient cannot stop and that does not match how they feel (pseudobulbar affect). Both cough on thin fluids. That cough is aspiration, and aspiration pneumonia is what kills these patients.

• Myasthenia gravis← from “Every cranial motor nerve ends the same way. T…”

  Antibodies bind the nicotinic acetylcholine receptor, cross-link and internalise it, fix complement and flatten the folds of the endplate. A smaller group instead carry antibodies to MuSK, the muscle-specific kinase that clusters the receptor at the endplate; these are IgG4, so they do not fix complement - they break up the clustering itself. The safety margin is gone. The normal small fall in transmitter release with each successive impulse now drops the endplate below threshold, so the muscle works at first and fails with use - and the muscles with the thinnest margin, the eyelids, the eye muscles and the throat, fail first.

  Anti-AChR antibodies (anti-MuSK if negative), repetitive nerve stimulation showing a decrement or single-fibre EMG, CT chest for thymoma. Drugs that impair neuromuscular transmission - aminoglycosides, macrolides, fluoroquinolones, magnesium, some beta blockers - can tip a stable myasthenic into crisis, so check the list before you prescribe.

  You would find: Ptosis and double vision worse at the end of the day or after 60 seconds of sustained upgaze, recovering after rest or an ice pack on the lid. Voice going nasal and quiet as they count aloud to 50. Ptosis with normal pupils and no pain. In crisis the diaphragm goes - measure the forced vital capacity, because oxygen saturation stays normal until they are close to respiratory arrest.

• Sixth nerve palsy from raised intracranial pressure← from “Three nerves move the eye and one of them does…”

  Pressure rises anywhere inside the skull, the brain shifts down slightly, and the long thin sixth nerve is stretched and angled over the petrous ridge. The lateral rectus weakens and the eye will not turn outward. It is a false localising sign: it tells you the pressure is up, not where the lesion is.

  An isolated sixth nerve palsy earns three checks: the optic discs, the blood pressure, the glucose. In idiopathic intracranial hypertension it is vision, tracked on formal visual fields, not the diplopia, that is at stake.

  You would find: Horizontal double vision, worse looking toward the affected side and worse in the distance; the eye sits slightly turned in. Then look at the discs. Swollen optic discs (papilloedema) with headache that is worse lying flat, worse in the morning and worse on coughing, plus pulsatile whooshing in the ears, is idiopathic intracranial hypertension - typically a young woman with recent weight gain, and diagnosed only after imaging (including venography to exclude venous sinus thrombosis) and a high opening pressure with normal CSF. The same picture with any other focal sign means image the head.

What we give, and how it works

Open a drug to see what it binds, what that does to the cell, and what you then see in the patient.