Nervous system

The cortex is a map with an artery draped over it. Read the deficit backwards and it tells you which lobe, which side and which vessel — and when that same sheet of neurons fires together instead of in pattern, you get a seizure whose appearance is nothing more than the job of the patch that started it.

What it does

The cortex is a map, and so is its blood supply. Motor cortex runs down the front lip of the central sulcus (precentral gyrus), sensory cortex down the back lip (postcentral gyrus), with the body laid out upside down and badly out of proportion — face and hand occupy more strip than the whole trunk (the homunculus). Draped over that map: the middle cerebral artery (MCA) feeds the lateral convexity — face, hand, arm and the language cortex; the anterior cerebral artery (ACA) feeds the medial strip where the leg and foot sit; the posterior cerebral artery feeds the occipital lobe and visual cortex. The frontal eye field, in the caudal middle frontal gyrus, drives the eyes to the opposite side and sits in MCA territory too.

Language lives in one hemisphere: the left in about 95% of right-handed people and around 70% of left-handers (dominance). Two nodes and a cable. The inferior frontal gyrus (Broca) assembles the output and sits immediately next to the motor strip for face and hand. The posterior superior temporal gyrus (Wernicke) decodes what is heard and sits next to auditory cortex. The arcuate fasciculus joins them. All of it is MCA territory.

Attention to space is not shared evenly between the hemispheres. The left hemisphere attends mainly to the right half of the world; the right parietal cortex, especially the temporoparietal junction, attends to both halves. Together they give you a seamless field you never have to think about.

What goes wrong

Cortical stroke — reading the artery off the patientAphasia — Broca, Wernicke, conduction, globalHemispatial neglect and anosognosiaFocal seizure from cortex, with or without spread to bilateral tonic-clonicTodd paresis — the seizure that looks like a stroke

What we give

Thrombolysis — recombinant tissue plasminogen activatorsAntiplatelet agentsSodium-channel blocking anti-seizure medicinesLevetiracetam

Two neurones in series carry the command to move: the first crosses in the medulla and hands over in the cord. Where you break the chain decides whether the limb ends up stiff and brisk or floppy and wasted.

What it does

The command runs through two neurones in series. The upper motor neurone arises chiefly from the motor strip of the frontal lobe (precentral gyrus), with contributions from premotor, supplementary motor and parietal cortex, runs down through the internal capsule and brainstem and ends in the cord, mostly on interneurones rather than directly on the motor neurone. The lower motor neurone starts in the anterior horn, leaves through the nerve root and peripheral nerve, and ends on muscle. Only the lower one touches muscle — it is the final common pathway.

Around 85% of corticospinal fibres cross to the other side in the lower medulla (pyramidal decussation) and run down the side of the cord as the lateral corticospinal tract; most of the small uncrossed remainder descends as the anterior corticospinal tract and crosses at segmental level. So the left cortex drives the right side of the body, but by the time the tract is in the cord it is already on the same side as the muscles it serves.

The descending motor system does not only excite. Acting through inhibitory interneurones in the cord, it holds the cord's own reflex circuits in check and damps the stretch reflex — and this restraint comes mainly from the reticulospinal and other brainstem pathways that travel alongside the corticospinal tract, not from the pyramidal fibres themselves. The spinal reflex arc is intact and ready to run without it.

What goes wrong

Ischaemic stroke of the internal capsule (lacunar pure motor stroke)Spinal cord compression (metastasis, trauma, cervical spondylotic myelopathy)Motor neurone disease (amyotrophic lateral sclerosis)Nerve root compression (radiculopathy) — the pure lower motor neurone lesion

What we give

Alteplase / tenecteplase (thrombolytics, recombinant tissue plasminogen activator)Baclofen (central antispasticity agent, GABA-B agonist)Botulinum toxin type A (focal chemodenervation)Riluzole (glutamate-modulating neuroprotective agent)

Two sensory highways run up the spinal cord and cross the midline in different places, which is why one lesion can wipe out pin and temperature down one side of the body while vibration is lost down the other.

What it does

Fine touch, vibration and joint position sense (proprioception) enter the cord and run straight up the back of it on the SAME side, only crossing the midline far higher up, in the lower medulla, as the internal arcuate fibres leaving the gracile and cuneate nuclei (dorsal column-medial lemniscus pathway).

Pain and temperature fibres enter the cord, travel only one or two segments up or down in Lissauer's tract, then synapse in the dorsal horn. The second neurone crosses the midline and ascends on the OPPOSITE side (spinothalamic or anterolateral pathway).

Those crossing pain and temperature fibres squeeze through the middle of the cord, just in front of the central canal (anterior white commissure).

What goes wrong

Brown-Sequard syndrome (hemisection of the cord)Syringomyelia (fluid cavity in the centre of the cord)Subacute combined degeneration (vitamin B12 deficiency)Anterior spinal artery occlusion (anterior cord syndrome)Diabetic peripheral neuropathy (length-dependent, small and large fibre)

What we give

Vitamin B12 replacement (hydroxocobalamin)Tricyclic antidepressant (amitriptyline)Gabapentinoid (pregabalin)Corticosteroid (dexamethasone)

A dopamine-tuned loop that decides how much movement gets through: starve it of dopamine and the patient freezes, take away its brake and the patient writhes.

What it does

The substantia nigra pars compacta sends dopamine to the striatum (the nigrostriatal pathway). Dopamine excites the go pathway through D1 receptors and inhibits the stop pathway through D2 receptors. Both actions point the same way: dopamine turns movement on.

Two pathways run through the loop. The direct pathway releases the thalamus from inhibition and lets a movement out (go). The indirect pathway runs through the subthalamic nucleus, which drives the globus pallidus interna to clamp the thalamus shut (stop). This loop tunes movement; it does not carry the command, which stays in the corticospinal tract.

Cholinergic interneurons inside the striatum release acetylcholine, which opposes dopamine. What matters is not the dopamine level alone but the dopamine-to-acetylcholine ratio (a balance, not a number).

What goes wrong

Parkinson diseaseDrug-induced parkinsonism (and acute dystonic reaction)Tardive dyskinesiaHuntington diseaseHemiballismus

What we give

Levodopa with a peripheral decarboxylase inhibitor (carbidopa or benserazide)Dopamine agonistsAntimuscarinics (central anticholinergics)Tetrabenazine (VMAT2 inhibitor)

The cerebellum does not start movements — it checks them, comparing what the cortex ordered against what the body actually did and correcting the difference thousands of times a second; break it and power and sensation are untouched, so what you see is clumsiness on the same side as the lesion, and what kills is that all of this sits in a rigid box in front of the brainstem.

What it does

The cerebellum does not initiate movement and carries no command to any muscle. It receives a copy of every motor plan from the cortex (relayed through the pontine nuclei) and, at the same moment, a running report of what the body actually did — from muscle spindles, tendon organs, the vestibular apparatus and the eyes. It compares the two and sends a correction back through the deep nuclei to the thalamus and motor cortex [the Purkinje cells are the sole output of the cerebellar cortex and they inhibit the deep nuclei, which are themselves the output of the cerebellum as a whole].

The wiring crosses twice. A cerebellar hemisphere talks to the opposite motor cortex — the output crosses in the superior cerebellar peduncle — and that cortex drives the opposite side of the body, crossing again in the medulla. Two crossings cancel out.

The cerebellum is divided by function down its length. The midline strip (vermis) and the small lobe tucked under it (flocculonodular lobe) run the trunk, stance, walking and eye movements, wired mainly to the vestibular nuclei. The two big lateral hemispheres run the limbs — especially fast, fine, distal movement — wired to the cerebral cortex.

What goes wrong

Cerebellar infarct — posterior circulation strokeMalignant cerebellar swelling — space-occupying infarct and hypertensive cerebellar haemorrhageAlcohol-related cerebellar degeneration, and Wernicke encephalopathyDrug-induced cerebellar toxicityMidline lesions — vermis and flocculonodular lobe

What we give

Thiamine (vitamin B1)Antiplatelet — aspirin, with short-term clopidogrel added early after minor stroke or high-risk TIAVestibular sedative and antiemetic — prochlorperazine (a phenothiazine blocking D2, H1 and muscarinic receptors)Sodium channel blocking antiseizure drug — phenytoin (carbamazepine blocks the same channel, but is handled quite differently by the body)

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 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 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).

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.

What goes wrong

Lateral medullary stroke (Wallenberg syndrome)Locked-in syndromeUncal herniation from raised intracranial pressureCentral respiratory depressionNeurogenic shock

What we give

Alteplase (recombinant tissue plasminogen activator, tPA)Hyperosmolar agentsOpioids (mu agonists)Vasopressors (alpha-1 agonists)

Twelve pairs of nerves leaving the brain and brainstem to run the eyes, the face, the swallow and the voice - each testable in a couple of minutes at the bedside, and each with a palsy that looks like nothing else.

What it 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.

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.

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.

What goes wrong

Third nerve palsyBell palsyBulbar and pseudobulbar palsyMyasthenia gravisSixth nerve palsy from raised intracranial pressure

What we give

Corticosteroid (glucocorticoid)Antimuscarinic (anticholinergic) for secretionsAcetylcholinesterase inhibitorCarbonic anhydrase inhibitor

A segmented cable that ends at L1 — where the lesion sits in cross-section tells you exactly what the patient has lost, and whether you are calling a surgeon tonight.

What it does

The cord tapers and stops at the L1-L2 level in an adult (conus medullaris). Below that the canal holds only a loose bundle of lumbar and sacral nerve roots floating in CSF (cauda equina).

Three tracts matter, and they cross in three different places. Movement comes down the side of the cord having already crossed in the medulla (lateral corticospinal tract). Fine touch, vibration and joint position run up the back of the cord on the same side and cross in the medulla (dorsal columns, via the internal arcuate fibres to the medial lemniscus). Pain and temperature cross inside the cord itself within a segment or two, through the anterior white commissure, then run up the opposite anterolateral quadrant (spinothalamic tract).

Fibres are stacked by body part. In the lateral corticospinal and spinothalamic tracts the sacral fibres lie furthest out and the cervical/arm fibres closest to the centre (somatotopic lamination), and the pain and temperature fibres decussate in the anterior white commissure, just in front of the central canal.

What goes wrong

Metastatic (malignant) spinal cord compressionCauda equina syndromeSyringomyeliaSubacute combined degeneration (B12 deficiency)Spinal shock, then spasticity and autonomic dysreflexia

What we give

Glucocorticoid (dexamethasone)GABA-B agonist (baclofen)Vitamin B12 replacement (hydroxocobalamin)Gabapentinoid (pregabalin)

A peripheral nerve is a bundled cable of axons wrapped in myelin: the axon is the wire, carrying the impulse and fed entirely from a cell body that may be a metre away, and the myelin is the insulation that makes it fast. Almost every neuropathy you will meet is one of those two failing — the longest wires starving, the insulation attacked, or the cable squashed in a tunnel — and which one it is decides what you find, what the tests show and what you can do about it.

What it does

A nerve fibre has two parts that fail separately. The axon is the conducting wire. The myelin is insulation, made by Schwann cells that each wrap one segment of one axon, with bare gaps between them (nodes of Ranvier) where the sodium channels are packed. The impulse jumps node to node (saltatory conduction), so a large myelinated fibre conducts at about 40 to 70 m/s while a bare unmyelinated fibre manages about 1 m/s. Strip the myelin and the impulse must crawl along the membrane, or stop altogether (conduction block); cut or starve the axon and the wire is simply gone, and the muscle and skin it supplied are denervated.

The axon builds almost none of its own protein. Mitochondria, channels and structural protein are made in the cell body (anterior horn cell for motor, dorsal root ganglion for sensory) and shipped down the axon by motor proteins running on microtubules (axonal transport), fast anterograde transport moving at a few hundred millimetres a day. The axon running from an L5 dorsal root ganglion to the tip of the great toe is close to a metre long. Its oxygen and glucose come from small vessels in and along the nerve (vasa nervorum); these anastomose along its length, but there are watershed zones with little reserve once many small vessels are diseased at once.

Not all fibres are the same size, and size decides both what they carry and whether a machine can see them. Large myelinated fibres carry motor output to muscle, vibration, joint position sense and light touch, and they are the afferent limb of the tendon reflexes. Thinly myelinated and unmyelinated fibres carry pain, temperature, and the postganglionic sympathetic output that drives sweating and vascular tone. Nerve conduction studies only record from the large myelinated fibres.

What goes wrong

Diabetic distal symmetrical polyneuropathyGuillain-Barre syndromeEntrapment neuropathy — carpal tunnel and its cousinsNeuropathic pain from a damaged nerve

What we give

Glycaemic control, with metformin as the usual first agentIntravenous immunoglobulin, or plasma exchangeGabapentinoidsTricyclic antidepressants, and the SNRI duloxetine — same idea, different collateral

The single synapse between the nervous system and voluntary muscle: the nerve terminal releases acetylcholine, a receptor on the muscle turns that chemical signal back into an electrical one, and an enzyme wipes the cleft clean within a millisecond — three steps, and almost every disease on this page breaks exactly one of them while almost every drug acts at one of the three.

What it does

An action potential arriving at the motor nerve terminal opens voltage-gated calcium channels of the P/Q type in the terminal membrane. Calcium rushes in and makes vesicles already docked at the release sites fuse with the membrane and dump their acetylcholine (ACh) into the cleft. The docking and fusion machinery is a set of proteins called SNAREs — SNAP-25, syntaxin and synaptobrevin (VAMP). Release is quantal: one vesicle is one packet of roughly 5000 to 10000 molecules, and a single impulse releases many packets at once (estimates vary with species and method; human quantal content is usually measured in the tens).

ACh diffuses about 50 nm across the cleft and binds nicotinic ACh receptors, packed at enormous density on the crests of the junctional folds. Two ACh molecules must bind (at the two sites formed by the alpha subunits) before the receptor — which is itself an ion channel gated by the ligand — opens; it is a non-selective cation channel, and the net inward current is carried mainly by sodium, producing a local depolarisation (the endplate potential). Voltage-gated sodium channels sitting in the depths of the folds convert that into a muscle action potential. Normal release generates an endplate potential three to five times larger than is needed to reach threshold. That margin is called the safety factor.

Acetylcholinesterase (AChE) sits anchored in the basal lamina of the cleft, working close to the physical limit of how fast an enzyme can work. It splits ACh into choline and acetate within about a millisecond, before most molecules get the chance to bind a second receptor; the choline is pulled back into the terminal and rebuilt into ACh. Because the transmitter is cleared this fast, and because of the safety factor, one nerve impulse produces one muscle fibre action potential — the transmitter itself does not accumulate in the cleft from one impulse to the next. (Mechanical tension in the whole muscle does summate at high firing rates — that is tetanus — but it summates in the contractile apparatus, not at this synapse.)

What goes wrong

Myasthenia gravisLambert-Eaton myasthenic syndromeBotulismCholinergic crisis and organophosphate poisoningResidual neuromuscular blockade after anaesthesia

What we give

Acetylcholinesterase inhibitorsImmunosuppression and antibody removal for myasthenia gravisNon-depolarising neuromuscular blockersSuxamethonium (a depolarising blocker)

The two-neuron motor system that runs everything you do not think about — heart rate, vessel tone, pupils, sweat, gut, bladder — using essentially two transmitters, acetylcholine and noradrenaline, sorted into receptor subtypes that decide which organ responds to which drug.

What it does

Both halves run through two neurons in series with a ganglion between them. Sympathetic fibres leave the cord from T1 to L2 (thoracolumbar), the first neuron is short and the ganglion sits close to the spine in the sympathetic chain, so the second neuron is long. Parasympathetic fibres leave in cranial nerves III, VII, IX and X and from S2 to S4 (craniosacral), the first neuron is long and the ganglion sits in or near the target organ, so the second neuron is very short. Every first neuron in both systems releases acetylcholine onto nicotinic receptors in the ganglion (Nn). The adrenal medulla is the exception that proves the rule: its chromaffin cells are modified second neurons that never grew axons, so instead of a synapse they release catecholamines straight into the blood — roughly 80 per cent adrenaline, the rest noradrenaline.

The second synapse is where the receptor subtypes live, and they are the whole map. Sympathetic second neurons release noradrenaline onto alpha-1 (vascular smooth muscle, bladder neck and prostate, pupil dilator, the small Muller muscle that helps hold the upper lid up), alpha-2 (mostly on the nerve terminal itself as a brake on further release, and in the brainstem), beta-1 (SA node, AV node, ventricle, renin-releasing cells of the kidney), beta-2 (bronchial smooth muscle, skeletal muscle arterioles, uterus, liver) and beta-3 (bladder detrusor, fat). Parasympathetic second neurons release acetylcholine onto muscarinic receptors: M1 in stomach and brain, M2 on the SA and AV nodes and atria, M3 on glands and on smooth muscle everywhere — pupillary sphincter, ciliary muscle, bronchi, gut, detrusor. Sweat glands break the pattern: they are sympathetic but their nerves release acetylcholine onto muscarinic receptors.

What each receptor does to the cell is fixed and short. Alpha-1 is Gq: it raises intracellular calcium and the smooth muscle contracts. Beta receptors are Gs: they raise cyclic AMP, which in cardiac muscle means faster and harder, and in smooth muscle means relax. M2 is Gi: it lowers cyclic AMP and opens potassium channels, so the SA node cell hyperpolarises, drifts to threshold more slowly and the heart slows, and AV conduction drags. M3 is Gq again: contraction and secretion.

What goes wrong

Diabetic autonomic neuropathyHorner syndromeAnticholinergic (antimuscarinic) effects and anticholinergic burdenVasovagal (reflex) syncopeOrganophosphate poisoning (cholinergic crisis)

What we give

Muscarinic antagonists (antimuscarinics)Alpha-1 agonistBladder antimuscarinics versus beta-3 agonistsTopical alpha agonist used diagnostically

Two sensory pathways wired so orderly that the shape of what the patient has lost tells you where the lesion is before any scan: for the eye, whether the defect respects the vertical midline and whether both eyes lose the same half of the world; for the ear, whether sound cannot get in or the cochlea cannot code it.

What it does

Split each retina down the middle. The half nearer the nose (nasal retina) looks out at the outer half of the world (temporal field) and its fibres cross at the optic chiasm. The half nearer the temple (temporal retina) looks at the inner field and stays on its own side. So there are three zones: in front of the chiasm a nerve carries one eye only; at the chiasm the crossing fibres of both eyes are bundled together in the middle; behind it every fibre carries the opposite half of the visual world from both eyes at once.

The map stays orderly all the way back, but it is upside down and it splits. Fibres from the lower retina (which see the upper field) swing forward around the temporal horn before turning back (Meyer loop); fibres from the upper retina (lower field) run straight back through the parietal white matter. Both end in the calcarine cortex of the occipital lobe, where the macula is given a huge area at the occipital pole, and that pole is fed by both the posterior and the middle cerebral artery.

The pupil light reflex is a separate loop that never reaches the cortex. Light in one eye runs up the optic nerve, and the pupil fibres leave the optic tract BEFORE the lateral geniculate to reach the pretectal nucleus in the midbrain, which drives BOTH Edinger-Westphal nuclei; parasympathetic fibres then ride on the outside surface of the third cranial nerve to constrict both pupils — the lit one (direct) and the other one (consensual).

What goes wrong

Pituitary tumour compressing the optic chiasmOptic neuritisHomonymous hemianopia and quadrantanopia after strokeConductive hearing loss: otitis media with effusion and chronic suppurative otitis mediaSensorineural hearing loss

What we give

Dopamine agonistsCorticosteroids, high-doseAntiplatelet agentsTopical fluoroquinolone ear drops, with aural toilet

Three membranes wrap the brain and the fluid between them floats it, cushions it and buys space — so every disease here is either something growing in a space that should not have anything in it, or fluid that cannot get out of a box that will not stretch.

What it does

Three layers, and what matters is the spaces between them. The dura is tough and adherent to the inner table of the skull, most firmly at the sutures; the middle meningeal artery runs in a groove on the inner table beneath the thin squamous temporal bone at the pterion — outside the dura, between dura and bone. The arachnoid sits against the inner face of the dura with no real gap — only a potential cleavage plane (the subdural space) that the bridging veins cross on their way from the cortex to the dural venous sinuses. The pia is applied directly to the brain surface. The only genuine space is the one between arachnoid and pia (subarachnoid space): it holds the CSF, and the big arteries of the circle of Willis and their branches run through it, bathed in fluid rather than supported by tissue.

CSF is secreted, not simply filtered. The choroid plexus in each ventricle actively pumps sodium into the ventricle using Na/K-ATPase on its apical (CSF-facing) membrane, with carbonic anhydrase supplying the bicarbonate and hydrogen ions that drive the exchangers; water follows osmotically. About 500 mL is made a day against a total volume of only about 150 mL, so the whole pool is replaced three or four times daily. It flows lateral ventricles to third (through the foramina of Monro), down the cerebral aqueduct to the fourth, out through the foramina of Luschka and Magendie into the subarachnoid space, then over the convexities to be absorbed passively down a pressure gradient through the arachnoid granulations into the dural venous sinuses (with a further share leaving along cranial nerve sheaths and meningeal lymphatic routes).

The skull is a rigid box holding brain, blood and CSF, and the three volumes must add to a constant (Monro-Kellie doctrine). Add a fourth thing — a haematoma, a tumour, oedema — and CSF is displaced into the spinal sac and venous blood is squeezed out first, so pressure barely moves. Once those buffers are spent, compliance is gone and the curve turns near-vertical: a few more millilitres now costs a large jump in pressure. Normal intracranial pressure in a supine adult is roughly 5-15 mmHg, and what perfuses the brain is the difference between the pressures either side of it — cerebral perfusion pressure = mean arterial pressure minus ICP.

What goes wrong

Bacterial meningitisExtradural (epidural) haematomaSubdural haematomaSubarachnoid haemorrhageHydrocephalus and raised intracranial pressure

What we give

Third-generation cephalosporinsCorticosteroids (glucocorticoids)Osmotherapy (hyperosmolar agents)Dihydropyridine calcium channel blocker

Two pairs of arteries feed the brain - the internal carotids in front, the vertebrals behind - and they join at the base of the brain in a ring, the circle of Willis, that can reroute flow between them; beyond that ring each branch waters its own patch of brain, with only thin surface anastomoses between territories and none at all for the deep perforators, so where the blockage sits tells you which part of the patient stops working.

What it does

The brain has two inflows. The internal carotids (anterior circulation) each give off the ophthalmic artery to the eye, then divide into the anterior cerebral artery (ACA) and the middle cerebral artery (MCA). The vertebral arteries run up through the transverse foramina of the cervical vertebrae, join to form the basilar artery (posterior circulation), and supply the brainstem and cerebellum through their own branches (pontine perforators, PICA, AICA and the superior cerebellar arteries) and the thalami and occipital lobes through the posterior cerebral arteries (PCA). The circle of Willis joins the two systems: the anterior communicating artery bridges the two ACAs, and a posterior communicating artery on each side runs from the internal carotid back to the PCA. A complete, well-formed ring is the exception rather than the rule - anatomical series put it at roughly a fifth to a half of people, with hypoplastic or absent communicating segments in the rest. Every one of those junctions is a branch point where the vessel wall is structurally weakest.

Beyond the ring each artery waters a fixed map. The cortical branches are functional end arteries: they are linked only by thin leptomeningeal (pial) anastomoses over the surface, enough to keep tissue alive for a while but not enough to prevent infarction. The deep perforators have no anastomoses at all and are true end arteries. The ACA runs over the corpus callosum and supplies the medial surface of the hemisphere - the leg and foot part of the motor and sensory strip. The MCA fans out over the lateral convexity: face and arm on the strip, the language areas of the dominant hemisphere (usually left), the attention networks of the non-dominant hemisphere, and the optic radiation passing beneath. The PCA supplies the occipital cortex and the thalamus. The brainstem gets tiny perforators straight off the basilar, and there the long tracts (already crossed or about to cross) sit millimetres from cranial nerve nuclei that have not crossed.

The brain is about 2 percent of body weight, takes about 15 percent of the cardiac output and consumes about 20 percent of the body's oxygen, at roughly 50 mL of blood per 100 g of brain each minute. It stores no oxygen and only a trivial amount of glucose as astrocytic glycogen. Small arteries constrict when pressure rises and dilate when it falls, holding flow steady across a mean arterial pressure of roughly 60 to 150 mmHg (autoregulation - the classic figures; the plateau is narrower and more variable between individuals than the textbook curve suggests); carbon dioxide is the most potent physiological cerebral vasodilator. Below about 20 mL/100 g/min neurons stop firing but stay alive - this is the penumbra, kept going by collateral trickle. Below about 10 mL/100 g/min they die. Chronic hypertension shifts the whole autoregulatory range upward.

What goes wrong

Middle cerebral artery territory infarct (embolic or thrombotic)Posterior circulation stroke (vertebrobasilar)Lacunar infarct (small vessel disease)Watershed (border zone) infarctionAneurysmal subarachnoid haemorrhage

What we give

Fibrinolytics (thrombolysis)Antiplatelet agentsOral anticoagulantsNimodipine (dihydropyridine calcium channel blocker)

A sheet of capillary endothelium sealed by tight junctions that decides what reaches the brain — and therefore why some drugs work centrally and others cannot, why CNS infection is hard to treat, and how the brain swells.

What it does

Brain capillaries have no gaps. The endothelial cells are welded edge to edge by tight junctions (claudin-5, occludin) and have almost no pores and very little vesicle traffic, so nothing slips between cells — everything must be taken through them.

To cross a cell you must be small and fat-soluble (lipophilic) — oxygen, carbon dioxide, alcohol, anaesthetic gases, ammonia — or have a carrier: glucose on GLUT1, large neutral amino acids and levodopa on LAT1.

The blood-facing (luminal) membrane is studded with efflux pumps (P-glycoprotein) that catch lipophilic molecules that did get in and throw them back into the blood.

What goes wrong

Bacterial meningitisVasogenic oedema around a tumour, metastasis or abscessHepatic encephalopathyCNS sanctuary — treatment fails behind an intact barrierIschaemic stroke: cytotoxic oedema, then barrier breakdown

What we give

Third-generation cephalosporin (ceftriaxone or cefotaxime), plus benzylpenicillin or amoxicillin when Listeria is a riskDexamethasone (corticosteroid)Osmotic therapy — mannitol or hypertonic salineLevodopa with carbidopa (a peripheral decarboxylase inhibitor)

Intracranial pressure is the pressure inside a sealed bone box that holds brain, blood and cerebrospinal fluid; because the box cannot expand, anything new inside it has to push something else out, and once the box runs out of give the pressure climbs fast and squeezes the brain against the only exits it has.

What it does

The adult skull is a rigid container of roughly 1700 mL holding three things: brain tissue (about 1400 g), blood (about 150 mL) and cerebrospinal fluid (about 150 mL). Their volumes must add up to the same total at all times, so if one grows, another must shrink (the Monro-Kellie doctrine). Normal intracranial pressure in a supine adult is about 7-15 mmHg. Measured at lumbar puncture in the lateral decubitus position, normal opening pressure is about 6-20 cm H2O; 20-25 cm H2O is borderline and 25 cm H2O or more is accepted as raised (this is the threshold used in the diagnostic criteria for idiopathic intracranial hypertension).

The give comes from two things that can be pushed out: CSF, squeezed down into the spinal sac and reabsorbed faster, and venous blood, drained out of the compliant cerebral veins and sinuses. Those buffers are small and they run out. Plot pressure against volume and the line is nearly flat at first, then it turns a corner and goes almost vertical: the same extra millilitre that did nothing early raises pressure enormously late (falling compliance).

The brain has no fuel reserve and needs continuous flow. What drives that flow is cerebral perfusion pressure = mean arterial pressure − intracranial pressure (CPP = MAP − ICP), with roughly 60-70 mmHg the usual target. Arterioles autoregulate flow across a MAP of about 50-150 mmHg, and they are exquisitely sensitive to carbon dioxide: a rising PaCO2 dilates them and adds blood volume, a falling PaCO2 constricts them and takes blood volume away.

What goes wrong

Raised intracranial pressure — the box is fullDecompensation — the extradural haematoma and its lucid intervalCushing reflex — the brainstem's last resortHerniation — brain forced through the gapsIdiopathic intracranial hypertension

What we give

Hyperosmolar therapy — mannitol (and hypertonic saline as its alternative)Corticosteroid — dexamethasoneIntravenous anaesthetic sedation — propofolCarbonic anhydrase inhibitor — acetazolamide