Brainstem
A thumb-sized stalk carrying every motor and sensory tract between brain and body, holding the nuclei of cranial nerves three to twelve, the switch that keeps you awake, and the centres that drive breathing and blood pressure — so a lesion the size of a pea can kill you.
What it normally does
Long tracts run through the brainstem and cross over at set levels — motor fibres cross low in the medulla (pyramidal decussation), so the body is controlled from the opposite side. Cranial nerve nuclei, by contrast, serve the face and head on their own side (the trochlear nucleus is the exception — its fibres cross before leaving the brainstem to supply the opposite superior oblique).
A single brainstem lesion gives weakness or numbness of the face on one side and the body on the other — crossed signs — which no cortical stroke can do.
A diffuse net of neurons runs the length of the brainstem core and projects up through the thalamus to the whole cortex, keeping it awake and alert (the reticular activating system).
Damage to the brainstem core, or pressure on it, causes coma — the cortex may be intact but nothing is switching it on.
The medulla holds the respiratory centres (with modulation from the pons), which sense arterial CO2 indirectly through the pH of the surrounding brain and cerebrospinal fluid and set the rate and depth of breathing automatically, without conscious input.
Medullary damage or drug suppression stops breathing while the patient is unconscious and cannot compensate.
The medulla also holds the vasomotor centre, which sets baseline sympathetic tone to blood vessels and the heart. Its baroreceptor input arrives from the carotid sinus via the glossopharyngeal nerve and from the aortic arch via the vagus, both terminating in the nucleus tractus solitarius.
Losing this output causes shock with a slow heart rate, and rising pressure on the brainstem produces the hypertension-plus-bradycardia of the Cushing reflex — the bradycardia being the baroreflex answering the hypertension.
What goes wrong
- Lateral medullary stroke (Wallenberg syndrome)← from “Long tracts run through the brainstem and cros…”
The vertebral artery, or less often the posterior inferior cerebellar artery, blocks, killing the outer wedge of the medulla. That wedge contains the spinothalamic tract carrying pain and temperature from the opposite side of the body, the spinal trigeminal nucleus and tract carrying pain and temperature from the same side of the face, the vestibular nuclei, the nucleus ambiguus (motor supply to pharynx and larynx), the inferior cerebellar peduncle, and the descending sympathetic fibres.
Crossed sensory loss plus dysphagia plus Horner equals lateral medulla. Nil by mouth until a formal swallow assessment: aspiration pneumonia is the leading early complication and the main reason these patients deteriorate in the first week.
You would find: Loss of pain and temperature on one side of the face and the other side of the body, with vertigo, nystagmus, hoarse voice, ipsilateral limb ataxia, inability to swallow safely, and a droopy lid with a small pupil on the lesion side (Horner syndrome). Touch, vibration and power are preserved — the dorsal columns and the corticospinal tract sit medially, outside the infarct — which surprises students.
- Locked-in syndrome← from “A diffuse net of neurons runs the length of th…”
The basilar artery occludes and infarcts the base of the pons. Every descending motor fibre to the body and to the lower cranial nerves is destroyed, but the reticular activating system sits dorsally, behind the lesion, and survives, as do the midbrain circuits for vertical eye movement.
Test vertical gaze in every unresponsive patient. Consciousness sits in the brainstem core, motor output sits in front of it, and a pontine infarct can take one without the other.
You would find: The patient is fully awake and fully aware but cannot move or speak. The only preserved movements are vertical gaze and blinking — so you ask them to look up for yes. Easily and disastrously mistaken for coma.
- Uncal herniation from raised intracranial pressure← from “A diffuse net of neurons runs the length of th…”
An expanding mass — extradural haematoma, large hemispheric stroke, tumour — pushes the medial temporal lobe (uncus) over the tentorial edge onto the midbrain. It compresses the third cranial nerve, whose parasympathetic pupil-constricting fibres run superficially and go first, then squashes the reticular activating system and the corticospinal fibres in the cerebral peduncle.
Blown pupil plus dropping conscious state equals herniation until proved otherwise. Cushing reflex is a late and pre-terminal sign, not something to wait for.
You would find: A dilated unreactive pupil on the side of the mass, a falling Glasgow Coma Scale, then weakness on the opposite side. Later the Cushing reflex — rising blood pressure with a slowing pulse and irregular breathing — as the brainstem is compressed.
- Central respiratory depression← from “The medulla holds the respiratory centres (wit…”
Opioids, benzodiazepines or a medullary lesion suppress the CO2-sensing respiratory neurons. The drive to breathe falls, CO2 rises, and the rising CO2 fails to produce the usual increase in ventilation because the sensor itself is switched off. Hypercapnia then further depresses conscious state.
Saturation monitors miss this — they measure oxygenation, not ventilation. Count the respiratory rate and score the sedation level; that is what detects opioid-induced ventilatory impairment early. Naloxone and a bag-valve-mask should be at hand wherever parenteral opioids are given.
You would find: Slow shallow breathing, pinpoint pupils in the case of opioids, rousable then unrousable, and oxygen saturation that stays deceptively normal if supplemental oxygen is running. The gas shows a high CO2 with a respiratory acidosis.
- Neurogenic shock← from “The medulla also holds the vasomotor centre, w…”
Brainstem or high cervical cord injury cuts the descending sympathetic pathway from the medullary vasomotor centre. Arterioles lose their baseline constriction and dilate, and because the cardiac sympathetic outflow (T1-T4) is cut off as well, vagal supply to the heart is unopposed and the heart cannot speed up to compensate.
Hypotension plus bradycardia plus warm skin equals neurogenic, not haemorrhagic — but in a trauma patient you exclude bleeding before you accept that diagnosis, and the two can coexist. Fluid alone will not fix it, because the tank got bigger rather than emptier.
You would find: Hypotension with a slow heart rate and warm dry pink peripheries — the opposite of the cold clammy tachycardic patient in haemorrhagic shock. Trauma context: motorbike crash, diving injury, fall from a horse.
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.
- Binds
- Fibrin-bound plasminogen. Alteplase binds fibrin in the clot and the plasminogen stuck to it.
- Which does
- Converts plasminogen to plasmin on the clot surface. Plasmin chews up the fibrin mesh holding the thrombus together.
- So you see
- The basilar artery reopens, perfusion returns to pons and midbrain, and the deficit can reverse. Time matters brutally here — brainstem tissue with poor collateral supply dies fast.
- And the same mechanism causes
- Intracranial haemorrhage. The drug cannot tell a pathological clot from a useful haemostatic plug, so any small vessel that was quietly sealed can reopen and bleed — and in the brainstem a few millilitres of blood is catastrophic.
- Handling
- A non-contrast CT to exclude haemorrhage comes before the drug, always. Bleeding in a stroke unit means stopping the infusion, not adjusting it. Thrombolysis is not the end of the pathway: basilar occlusion is also an endovascular thrombectomy indication, so the CT angiogram and the call to the neurointerventional service happen in parallel, not after. Tenecteplase (single bolus) is an accepted alternative to alteplase in current Australian stroke guidelines; the choice and the dose belong to the stroke protocol, not to memory.
- Binds
- No receptor. Mannitol is an inert sugar alcohol that stays in the vascular compartment because the intact blood-brain barrier will not let it through.
- Which does
- Raises plasma osmolality, so water moves osmotically out of brain interstitium and cells into blood. Brain volume falls, so intracranial pressure falls.
- So you see
- Pupil may re-react, conscious state may lift, and the cone of temporal lobe pressing on the midbrain eases — for a few hours.
- And the same mechanism causes
- Mannitol is then filtered at the glomerulus and not reabsorbed, so it drags water and electrolytes into the urine — an osmotic diuresis that causes hypovolaemia and hypotension. Drop the blood pressure and you drop cerebral perfusion pressure, undoing the benefit. The same osmotic load explains the other two problems: mannitol that leaks into injured brain where the barrier is broken can pull water back in as plasma osmolality falls (rebound swelling), and heavy repeated dosing risks osmotic nephrosis and acute kidney injury.
- Handling
- Hypertonic saline is generally preferred when the patient is already hypovolaemic or hypotensive, because mannitol's diuresis worsens both. Monitor serum sodium and osmolality and keep the patient euvolaemic. Either agent only buys hours — the definitive treatment is removing or decompressing the mass, so the neurosurgical referral is made at the same time as the drug is given.
- Binds
- Mu opioid receptor, a Gi-coupled G protein receptor on medullary respiratory neurons.
- Which does
- Gi activation opens potassium channels and closes calcium channels, hyperpolarising the neuron. It fires less, and it becomes deaf to rising CO2.
- So you see
- Respiratory rate falls, breaths become slow and shallow, CO2 climbs. Pinpoint pupils come from the same drug acting in the midbrain, where mu agonists disinhibit the Edinger-Westphal nucleus and drive parasympathetic pupillary constriction.
- And the same mechanism causes
- Respiratory arrest. The analgesia and the apnoea are the same receptor in two places, so you cannot have one without risking the other.
- Handling
- Naloxone is a competitive mu antagonist — it displaces the opioid and breathing resumes, but its duration of action is shorter than that of most opioids, so the patient can re-sedate and needs observation and often repeat doses or an infusion. Titrate to respiratory rate, not to full reversal, in a patient who needs analgesia.
- Binds
- Alpha-1 adrenoceptors on vascular smooth muscle (noradrenaline also has beta-1 activity at the heart; phenylephrine is essentially pure alpha-1).
- Which does
- Gq coupling raises intracellular calcium in smooth muscle, so the arteriole constricts. Systemic vascular resistance rises.
- So you see
- Blood pressure rises and cerebral and spinal cord perfusion is restored in a patient whose own vasomotor centre has stopped driving the vessels.
- And the same mechanism causes
- The same constriction in gut, renal and skin beds — mesenteric ischaemia, digital necrosis, and tissue necrosis if a peripheral line extravasates. Squeezing every arteriole raises the pressure but starves the beds you were not aiming at. A pure alpha-1 agonist also raises afterload without any chronotropic support, so the baroreflex can slow an already bradycardic heart further.
- Handling
- Vasoconstrictors do not fix the bradycardia of neurogenic shock — that needs atropine, or a chronotropic agent or pacing if it is refractory — because the problem there is loss of cardiac sympathetic outflow leaving vagal tone unopposed. Noradrenaline, which supports rate as well as tone, is usually the agent of choice for this reason. Give it centrally where possible and only after volume status is addressed.
Crossed signs — face on one side, body on the other — localise the lesion to the brainstem and nowhere else. Then use the pupils: a fixed dilated pupil with a falling conscious state is uncal herniation squeezing cranial nerve three against the midbrain, and it earns an immediate CT and a neurosurgical call, not a routine neurology referral.
Now test whether it stuck
Reading this through is not the same as being able to reconstruct it. Every question in the bank is free, with a full debrief on each option.