Meninges and cerebrospinal fluid

What it normally 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.

  Explains why the same head knock produces three completely different pictures: arterial blood stripping dura off bone in a tight lens, venous blood spreading freely under the dura in a crescent, and arterial blood bursting straight into the CSF.

• 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).

  Explains why a block anywhere along that one-way pipe dilates everything upstream of it, why scarring of the granulations after blood or pus dilates everything, and why a drug that inhibits carbonic anhydrase turns production down.

• 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.

  Explains the lucid interval, why deterioration when it comes is sudden rather than gradual, the Cushing response, and why dropping blood pressure in a head injury is as dangerous as the clot itself.

• CSF is a clean, immunologically quiet compartment. Tight junctions between choroid plexus epithelial cells (blood-CSF barrier) and between cerebral capillary endothelial cells (blood-brain barrier) keep cells, large molecules and most water-soluble drugs out. Normal CSF has under 5 white cells per microlitre (mostly lymphocytes and monocytes), protein under about 0.45 g/L, glucose around two-thirds of the paired blood value, and is sterile. The immune point is not that the compartment is empty — there are border-associated macrophages in the meninges, perivascular spaces and choroid plexus — but that the CSF itself is a poor place to fight an infection: immunoglobulin and complement concentrations are a tiny fraction of those in plasma, so opsonisation is feeble and circulating neutrophils have to be recruited in from outside.

  Explains why a lumbar puncture reads like a report card — cells, protein, glucose ratio, Gram stain — why bacteria that reach this space multiply almost unopposed until neutrophils are recruited, and why antibiotics have to be chosen and dosed for a compartment they struggle to enter.

What goes wrong

• Bacterial meningitis← from “CSF is a clean, immunologically quiet compartm…”

  Organisms reach the subarachnoid space, usually from the nasopharynx through the bloodstream (Neisseria meningitidis, Streptococcus pneumoniae), sometimes directly through a skull base fracture or from the middle ear. In a compartment with almost no complement or antibody to opsonise them they multiply nearly unchecked before any defence arrives. Cell wall fragments then trigger a cytokine flood (TNF, IL-1); neutrophils are recruited across the now-leaky barrier and fill the subarachnoid space with pus. Three consequences follow from the anatomy above: the exudate blocks the arachnoid granulations and the basal cisterns, so CSF cannot drain (communicating hydrocephalus); the inflamed arteries running through that pus can thrombose, causing stroke; and cerebral oedema plus obstructed CSF raises ICP inside a box that cannot expand.

  Blood cultures, then treat — never delay the first antibiotic dose for a CT or a lumbar puncture; the LP can follow once it is safe. Vaccination has made Haemophilus influenzae type b and serogroup C meningococcal disease rare in Australia rather than abolishing them. Serogroup B now causes the large majority of invasive meningococcal disease, with W and Y making up most of the remainder (W surged in 2016-17 and fell back after MenACWY went onto the National Immunisation Program). Rates of both invasive meningococcal and invasive pneumococcal disease are substantially higher in Aboriginal and Torres Strait Islander people, particularly in central Australia and the Northern Territory — which is why meningococcal B vaccine is funded nationally for Aboriginal and Torres Strait Islander children. Add Listeria cover in the over-50s, pregnant women and the immunosuppressed.

  You would find: Fever, headache, neck stiffness and photophobia, with drowsiness or confusion — the classic triad of fever, neck stiffness and altered mental state is complete in fewer than half. Infants are non-specific: irritable, off feeds, bulging fontanelle. A non-blanching purpuric rash means meningococcaemia until proven otherwise. CSF: hundreds to thousands of neutrophils, protein up, glucose down to under 0.4 of the paired blood glucose (bacteria and neutrophils are consuming it). Viral meningitis gives lymphocytes, mildly raised protein, and a normal glucose ratio.

• Extradural (epidural) haematoma← from “The skull is a rigid box holding brain, blood …”

  A blow to the temple fractures the thin squamous temporal bone and tears the middle meningeal artery running in its groove. Arterial pressure peels the dura off the inner table of the skull — hard work, which is why the collection can enlarge relatively slowly at first and why it stops at the sutures where the dura is fused to bone, giving the tight biconvex lens on CT. While CSF and venous blood are being displaced, pressure hardly rises and the patient can look well: the lucid interval. Once compliance is exhausted the pressure curve goes vertical, the medial temporal lobe is forced through the tentorial notch (uncal herniation) and compresses the third cranial nerve and the midbrain.

  Lens shape, does not cross sutures, arterial, fast, young, lucid interval, same-side blown pupil. This is a surgical emergency measured in hours — the treatment is evacuation, not a drug.

  You would find: Young patient, temporal impact, brief knockout, then talks and deteriorates. The pupil goes first and on the same side as the clot — the parasympathetic fibres sit superficially on the third nerve and are compressed before the motor fibres — then ptosis and a down-and-out eye, then contralateral weakness, then the Cushing response: rising blood pressure, falling pulse, irregular breathing. Biconvex lens on CT that does not cross sutures but may cross the midline.

• Subdural haematoma← from “Three layers, and what matters is the spaces b…”

  Acceleration-deceleration makes the brain move inside the skull while the dural sinuses stay put, shearing the bridging veins as they cross the subdural plane. This is low-pressure venous blood, so it collects slowly and spreads freely under the dura — a crescent that crosses suture lines but is stopped by the dural reflections (the falx at the midline, the tentorium below). In older brains, atrophy has already stretched those veins across a wider gap, so a trivial knock tears them; add an anticoagulant or antiplatelet, or the atrophy of chronic heavy alcohol use, and the bleed can be silent for weeks while a membrane forms around it and the collection slowly expands.

  Crescent, crosses sutures, stops at the falx and tentorium, venous, slow, elderly, anticoagulated. A fluctuating confused older person on warfarin or a DOAC gets a CT head. Burr hole drainage for symptomatic chronic collections; middle meningeal artery embolisation is emerging as an adjunct that reduces recurrence.

  You would find: Acute: rapid deterioration after significant trauma, crescent of fresh hyperdense blood on CT. Chronic: an older person, weeks after a fall nobody thought much of, with headache, fluctuating confusion, drowsiness, or a slowly progressive hemiparesis — commonly mistaken for dementia or a stroke. On CT the chronic collection is dark (hypodense) as the blood breaks down.

• Subarachnoid haemorrhage← from “Three layers, and what matters is the spaces b…”

  The arteries of the circle of Willis run unsupported through the subarachnoid space. A saccular (berry) aneurysm at a branch point ruptures and arterial blood is injected straight into the CSF at systemic pressure, which is why the headache is instantaneous and why ICP can spike enough to cause immediate collapse. Blood in CSF is chemically irritant, giving meningism without infection. Then the delayed problems, all traceable to the same anatomy: blood clogs the arachnoid granulations and basal cisterns, so CSF stops draining and hydrocephalus follows; breakdown products around the bare vessels drive arterial narrowing and microvascular failure from about day 3 to day 14, causing delayed cerebral ischaemia; and rebleeding is the immediate threat until the aneurysm is secured.

  Worst headache of life, instant onset, CT then LP for xanthochromia at 12 hours. Aneurysm secured early by coiling or clipping. Nimodipine to reduce delayed cerebral ischaemia. Watch for hydrocephalus and for hyponatraemia.

  You would find: Thunderclap headache — worst ever, maximal within seconds — often with vomiting, neck stiffness and reduced consciousness. Non-contrast CT within six hours of onset, in a neurologically intact patient and read competently, is close to definitive; beyond that window, an LP at 12 hours or more from onset looks for xanthochromia, the yellow tinge of bilirubin that proves the blood was in the CSF before the needle was (a traumatic tap gives blood that clears between tubes and no xanthochromia). Risk factors that actually come up: hypertension, smoking, family history, autosomal dominant polycystic kidney disease.

• Hydrocephalus and raised intracranial pressure← from “CSF is secreted, not simply filtered. The chor…”

  CSF production is nearly constant and largely pressure-independent; drainage is not. Block the pipe — aqueduct stenosis, a posterior fossa tumour, a colloid cyst at the foramen of Monro — and every space upstream dilates while the ones downstream stay small (obstructive, or non-communicating). Scar the exit filter after meningitis or subarachnoid blood and the whole system dilates together (communicating). Either way, once compliance is spent, ICP climbs, cerebral perfusion pressure falls, and the brain is pushed towards the only exits it has: under the falx, through the tentorial notch, and finally the cerebellar tonsils into the foramen magnum, which compresses the brainstem and stops breathing.

  Papilloedema plus a focal deficit means image before any lumbar puncture — coning risk. The treatment for an obstructed ventricular system is mechanical: an external ventricular drain now, a ventriculoperitoneal shunt later. Drugs only buy time.

  You would find: Infants have open sutures, so the head simply grows: occipitofrontal circumference crossing centiles, a bulging fontanelle, and the sunsetting sign. In adults nothing can expand, so you get headache worse in the morning and on lying flat, vomiting, papilloedema, and a sixth nerve palsy that means nothing about location (a false localising sign — the abducens nerve has a long intracranial course and is tethered where it bends over the petrous ridge into Dorello's canal, so any downward shift of the brain stretches it). Normal pressure hydrocephalus in the elderly is the odd one out: gait apraxia, urinary incontinence and cognitive slowing with big ventricles and near-normal pressure. Cushing response and a falling GCS are late and pre-terminal.

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.