Neuroanatomy — Brainstem, Cranial Nerves & Spinal Cord

Overview

The brainstem houses the vital cardiorespiratory centres, the cranial nerve nuclei, and the ascending and descending tracts. Its anatomy underpins the neurological examination of coma (which cranial nerve sign localises the lesion) and the bedside reflexes used in brain-death testing.[1]

This topic covers the central nervous system from the cortex down to the conus: the four cortical lobes and their functions, the basal ganglia and their motor loops, the thalamus and hypothalamus, the limbic system, the brainstem and its cranial nerves, the cerebellum, the ventricular system and the flow of cerebrospinal fluid, the Circle of Willis and the cerebral arterial territories, the three long spinal tracts and their blood supply, the blood-brain barrier, and the autonomic nervous system. The exam asks for structure (name it), function (what does it do), and the clinical correlate (what sign does a lesion produce) - so each section below is built around that triad. [1]

The cerebral cortex

The cerebral cortex is the 2-4 mm grey-matter mantle of the cerebrum, thrown into gyri and sulci that triple its surface area. It is organised into four paired lobes (frontal, parietal, temporal, occipital) plus the insula (deep within the lateral sulcus) and the limbic lobe. Function is localised to gyri, so a focal lesion produces a focal deficit - the basis of cortical localisation.[1]

The cortex is built on the columnar principle: vertically oriented arrays of neurons (the cortical columns) are the functional units. The neocortex (six layers) makes up 90 per cent; the older allocortex (hippocampus, olfactory cortex) is three-layered. Brodmann mapped 52 cytoarchitectonic areas; the handful an intensivist must know are the primary motor (area 4, precentral gyrus), the primary somatosensory (areas 3, 1, 2, postcentral gyrus), the primary visual (area 17, calcarine cortex), the primary auditory (areas 41, 42, superior temporal), Broca's motor speech (areas 44, 45, inferior frontal, dominant hemisphere) and Wernicke's receptive language (area 22, posterior superior temporal, dominant hemisphere).[1]

The motor and sensory homunculi (Penfield's somatotopic maps) are exam staples. Both are drawn on the central sulcus: motor on the precentral, sensory on the postcentral. The body is inverted - the leg and foot are on the medial surface (paracentral lobule), the arm and hand over the convexity, the face and tongue most laterally and inferiorly. The areas devoted to the hand, lips and tongue are vastly enlarged relative to their size (cortical magnification), reflecting the density of their innervation. This map predicts the deficit: a small cortical stroke over the hand area weakens only the hand (a pure motor monoparesis that the unwary may attribute to a peripheral nerve).[1]

The basal ganglia

The basal ganglia are a group of deep grey-matter nuclei that initiate and smooth voluntary movement, control muscle tone and posture, and contribute to procedural (habit) learning. They do not themselves produce movement; they modulate the cortical motor areas through the thalamus in a loop (cortex → striatum → globus pallidus → thalamus → cortex).[1]

The components are: the striatum (caudate nucleus + putamen), the globus pallidus (internal and external segments, GPi and GPe), the subthalamic nucleus, and the substantia nigra (pars compacta SNc, pars reticulata SNr). The putamen + globus pallidus together form the lentiform nucleus. The caudate and putamen are the input zone (they receive from cortex); the GPi and SNr are the output zone (they inhibit the thalamus). [1]

The clinical payoff: Parkinson disease is degeneration of the SNc dopaminergic neurons - dopamine is lost, so the indirect pathway runs unchecked and the direct pathway is underactive; movement is globally suppressed (bradykinesia, rigidity, tremor). Huntington disease is degeneration of the striatal neurons of the indirect pathway (the GABA-ergic medium spiny neurons); suppression is lost, so excess, unwanted movement appears (chorea). A lesion of the subthalamic nucleus (classically a lacunar stroke) releases the most violent form - hemiballismus, wild flinging of the contralateral limb. Wilson disease (copper deposition in the basal ganglia, especially the putamen) gives a parkinsonian or choreiform picture with the pathognomonic copper ring at the corneoscleral limbus (the Kayser-Fleischer ring).[1]

The thalamus and hypothalamus

The thalamus is the great sensory and motor relay of the brain. It is a paired egg-shaped mass of grey matter that forms the lateral wall of the third ventricle (the two thalami are joined across the midline by the interthalamic adhesion). Every major sensory modality except olfaction synapses in the thalamus before reaching the cortex, and the cerebellum and basal ganglia relay through it on their way to the motor cortex. The intensivist must know the functional nuclei: [1]

• VPL (ventral posterolateral): body sensation (the medial lemniscus and spinothalamic tract terminate here) - the relay for contralateral body touch, pain, temperature, proprioception.
• VPM (ventral posteromedial): face sensation - the relay for the trigeminal system.
• VL (ventral lateral) and VA (ventral anterior): motor - the relay for the cerebellum and basal ganglia to the motor cortex.
• Lateral geniculate nucleus (LGN): vision (optic tract).
• Medial geniculate nucleus (MGN): hearing (inferior colliculus).
• Anterior nucleus: limbic (memory, emotion; part of the Papez circuit).
• Dorsomedial (DM) nucleus: prefrontal / executive. [1]

A unilateral thalamic lesion classically gives a thalamic (Dejerine-Roussy) syndrome: transient contralateral hemiparesis, then a distressing, persistent, treatment-resistant contralateral pain (thalamic pain) with allodynia, dysaesthesia and hemisensory loss.[1]

The hypothalamus is the master homeostatic regulator, sitting below the thalamus and forming the floor and walls of the third ventricle. Its nuclei control the autonomic nervous system, body temperature (the anterior hypothalamus dissipates heat - sweating, vasodilation; the posterior conserves it - shivering, vasoconstriction), hunger and satiety (ventromedial = satiety; lateral = hunger), thirst and water balance (supraoptic and paraventricular nuclei make ADH, via the supraopticohypophyseal tract to the posterior pituitary), the sleep-wake cycle and circadian rhythm (suprachiasmatic nucleus), and the endocrine axis (releasing hormones to the anterior pituitary via the hypophyseal portal system; oxytocin and ADH to the posterior pituitary). Hypothalamic lesions therefore cause a bewildering catalogue - diabetes insipidus (ADH loss), SIADH, poikilothermia or hyperthermia, hyperphagia and obesity, insomnia or somnolence, and (when severe) hypothalamic coma with autonomic storms, hyperthermia and cardiovascular instability.[1]

The limbic system

The limbic system is the ring of cortex and deep nuclei around the corpus callosum and diencephalon that governs emotion, motivation, memory and olfaction. Its core is the Papez circuit, the closed loop that encodes emotional memory: hippocampal formation → fornix → mammillary body → anterior nucleus of the thalamus → cingulate gyrus → parahippocampal gyrus → back to the hippocampus.[1]

The components to name: the hippocampal formation (dentate gyrus, hippocampus proper, subiculum) - consolidation of new declarative memory; the amygdala - fear and emotional valence; the mammillary bodies (on the floor of the hypothalamus); the anterior thalamic nucleus; the cingulate gyrus (above the corpus callosum); the parahippocampal gyrus (medial temporal); the fornix (the C-shaped output fibre bundle of the hippocampus); and the septal area. Olfaction is the only sensory modality that bypasses the thalamus on its first synapse - it reaches the cortex (the piriform cortex) directly, which is why smell has such immediate emotional power. [1]

The clinical correlates are exam favourites: Korsakoff syndrome (damage to the mammillary bodies and dorsomedial thalamus from thiamine deficiency in alcoholism) gives anterograde amnesia with confabulation; temporal lobe epilepsy arises in the hippocampus; Kluver-Bucy syndrome (bilateral amygdala damage) gives hyperphagia, hypersexuality, visual agnosia and emotional blunting; and hippocampal sclerosis is the commonest pathology in mesial temporal lobe epilepsy.[1]

The brainstem

• Midbrain - contains the cerebral peduncles, the substantia nigra, the red nucleus, and cranial nerves III and IV nuclei. The Edinger-Westphal nucleus (parasympathetic to the pupil) lies here.[1]
• Pons - contains CN V, VI, VII and VIII nuclei and the corticospinal fibres before they decussate.[1]
• Medulla - contains CN IX, X, XI and XII nuclei and the cardiorespiratory control centres (the dorsal respiratory group, ventral respiratory group, and the nucleus tractus solitarius), plus the pyramidal decussation of the corticospinal tracts.[1]

Each brainstem level carries a signature cluster of cranial nerve nuclei, which is why a brainstem lesion localises to its level on the cranial nerve examination alone: [1]

The cranial nerves

A CN III palsy gives a "down and out" eye with a dilated pupil (parasympathetic loss); an abducens (VI) palsy gives failure of abduction (a false-localising sign in raised intracranial pressure).[1]

A useful grouping for the viva: CN I and II are not true peripheral nerves - they are extensions (tracts) of the brain, myelinated by oligodendrocytes and wrapped in meninges, which is why multiple sclerosis (an oligodendrocyte disease) commonly causes optic neuritis. CN III, IV, VI, XI (motor) and the motor branch of V are the somatic motor group. CN V (sensory), VII, IX, X carry the branchial arch derivatives. CN VII, IX, X are the parasympathetic secretomotor group (lacrimal, salivary and thoracic/abdominal viscera). [1]

Brainstem reflexes (coma and brain-death assessment)

• Pupillary light reflex (afferent CN II, efferent CN III) - tests midbrain and the third nerve; a fixed dilated pupil suggests third-nerve compression (uncal herniation).[1]
• Corneal reflex (afferent CN V, efferent CN VII) - tests pons.[1]
• Gag reflex (afferent CN IX, efferent CN X) and cough reflex (CN X) - test medulla.[1]
• Oculocephalic (doll's-eye) reflex (afferent CN VIII, efferent CN III, IV, VI) - absent in brainstem injury; preserved in metabolic coma with an intact brainstem.[1]

[5]

The cerebellum

The cerebellum ("little brain") sits in the posterior cranial fossa beneath the tentorium, comprising only 10 per cent of brain volume but more than half of all its neurons. It does not initiate movement and is not consciously perceived; it coordinates and calibrates movement and posture by comparing the intended movement (from the cortex, via the pontine nuclei) with the actual movement (via the spinocerebellar proprioceptive input), then correcting the cortex and the descending motor tracts.[1]

Anatomically it has a midline vermis and two hemispheres, divided by the primary fissure into an anterior lobe and a much larger posterior lobe, with the small flocculonodular lobe (the vestibulocerebellum) tucked underneath. Three fibre bundles connect it to the brainstem: the superior cerebellar peduncle (the main outflow, to the red nucleus and thalamus - carries the dentatorubrothalamic tract), the middle cerebellar peduncle (the main inflow, the corticopontocerebellar fibres), and the inferior cerebellar peduncle (spinocerebellar and vestibulocerebellar inflow). [1]

Functionally there are three longitudinal zones: the vestibulocerebellum (flocculonodular - balance, eye movement; lesion = truncal ataxia and nystagmus), the spinocerebellum (vermis and paravermis - posture, gait and limb synergy; lesion = gait and trunk ataxia, dysmetria), and the cerebrocerebellum (the lateral hemispheres - planning and timing of skilled movement; lesion = dysmetria, dysdiadochokinesia, intention tremor, decomposition of movement). The cerebellar cortex has three layers - molecular, Purkinje, granular - and the deep cerebellar nuclei (fastigial, interposed, dentate) give the output. Every cerebellar pathway is double-crossed - the input crosses once to reach the cerebellum and the output crosses again to reach the thalamus - so a cerebellar lesion gives ipsilateral signs.[1]

The cerebellar sign cluster (the exam answer): ataxia (wide-based, staggering gait), dysmetria (past-pointing on finger-nose and heel-shin), intention tremor (worse as the target is approached), dysdiadochokinesia (impaired rapid alternating movement), nystagmus (coarse, toward the side of the lesion), scanning (staccato) dysarthria, rebound phenomenon (the outstretched limb swings wildly when released), and hypotonia with pendular reflexes. The lateral signs are ipsilateral; midline (vermian) lesions give truncal and gait ataxia out of proportion to the limbs. [1]

The ventricular system and CSF flow

The ventricular system is the cerebrospinal-fluid (CSF)-filled cavity within the brain, lined by ependyma. CSF is produced by the choroid plexus (the highly vascular tuft in the roofs of the lateral and fourth ventricles) at about 0.3-0.4 mL/min (roughly 500 mL/day); the total volume in the system at any moment is only about 150 mL (30 mL in the ventricles, 120 mL in the subarachnoid space), so it turns over about three times a day.[1]

The blockages that matter: obstruction within the ventricular system (aqueduct, fourth ventricle outlets, posterior fossa tumour) causes non-communicating (obstructive) hydrocephalus - the ventricles proximal to the block dilate and intracranial pressure rises. Block at the level of the arachnoid granulations (after subarachnoid haemorrhage, meningitis, or tumour) causes communicating hydrocephalus. The special syndrome to know is normal-pressure hydrocephalus - a communicating hydrocephalus with intermittently raised pressure - whose triad (gait apraxia, dementia, urinary incontinence) is potentially reversible by a ventricular shunt.[1]

The Circle of Willis

The Circle of Willis is the polygonal anastomotic ring at the base of the brain that interconnects the anterior (internal carotid) and posterior (vertebrobasilar) circulations. It sits in the interpeduncular cistern, surrounding the optic chiasm and the pituitary stalk. When complete it provides collateral flow: an occlusion of one feeding vessel can be offset by flow around the ring. [1]

The ring is complete in only about half of people - the ACoA, PCoA or one PCA is hypoplastic or absent in the rest. The named sites of aneurysm formation (where the bifurcation haemodynamics stress the wall) are, in descending order of frequency, the anterior communicating artery (the single commonest site, classically presenting with a bitemporal hemianopia from chiasmal compression), the posterior communicating artery (the classic surgical third-nerve palsy - the dilated pupil and ptosis, because the parasympathetic fibres ride on the surface of CN III where the PCoA aneurysm compresses them), and the middle cerebral artery bifurcation (M1-M2, the commonest site for an embolic stroke).[1][6]

The small perforating vessels off the circle supply the deep structures and are themselves high-yield: the medial and lateral lenticulostriate arteries (off the MCA and ACA) supply the basal ganglia and the internal capsule; the recurrent artery of Heubner (off the ACA) supplies the head of the caudate and the anterior limb of the internal capsule; the thalamoperforating and thalamogeniculate arteries (off the PCA) supply the thalamus; and the anterior choroidal artery (off the ICA) supplies the posterior limb of the internal capsule, the optic tract and the hippocampus - its occlusion gives the classic triad of hemiplegia, hemisensory loss and homonymous hemianopia. [1]

The cerebral artery territories

The cortical territory each artery supplies predicts the deficit from its occlusion, which is why the vascular map is examined as hard as the cortical map. The internal carotid terminally divides into the ACA and the MCA; the vertebrobasilar system ends in the two PCAs.[1]

The arterial territories explain why the time-critical treatments work the way they do: a proximal large-vessel occlusion in the MCA (M1) or internal carotid is the lesion amenable to mechanical thrombectomy, because the clot is retrievable and the territory is large; small-vessel (lacunar) occlusions deep in the basal ganglia are not. Reperfusion in the right window rescues the ischaemic penumbra (the hypoperfused but not yet infarcted tissue around the core).[1][2][3][4]

Spinal cord tracts

• Lateral corticospinal tract (motor): fibres cross in the medullary pyramidal decussation, so a cord lesion causes ipsilateral upper-motor-neuron weakness below the level.[1]
• Spinothalamic tract (pain and temperature): fibres cross within one or two segments at the cord level, so a lesion causes contralateral loss of pain and temperature below the level (Brown-Sequard pattern in hemi-cord injury).[1]
• Dorsal (posterior) columns (proprioception, vibration, fine touch): fibres cross in the medulla (the medial lemniscus), so a cord lesion causes ipsilateral loss below the level.[1]

In cross-section the cord is an H-shaped (butterfly) core of grey matter surrounded by white matter. The grey matter has a posterior (dorsal) horn (sensory, where the dorsal roots synapse) and an anterior (ventral) horn (lower motor neurons, where the ventral roots exit); the lateral horn (T1-L2) carries the sympathetic preganglionic neurons. The white matter is divided into dorsal columns (gracile fasciculus medially for the lower limb, cuneate laterally for the upper limb), the lateral columns (corticospinal laterally, spinothalamic anterolaterally, plus the spinocerebellar tracts), and the ventral columns. There are 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal); note there are 8 cervical roots but only 7 cervical vertebrae (C1 exits above C1; C8 exits below C7; below that every root exits below its vertebra). [1]

Cord blood supply

• The anterior spinal artery (from the vertebrals) supplies the anterior two-thirds of the cord, including the corticospinal and spinothalamic tracts - so anterior spinal artery syndrome spares the dorsal columns (proprioception and vibration intact) but causes bilateral motor and pain/temperature loss.[1]
• Two posterior spinal arteries supply the posterior third (the dorsal columns).[1]
• The artery of Adamkiewicz (a large segmental feeder, usually left, T9-L2) reinforces the anterior supply to the lower two-thirds; injury during aortic surgery or aortic dissection can infarct the cord.[1]
• The adult cord ends as the conus medullaris at L1-L2; below this the cauda equina is a collection of lumbosacral roots (a lumbar puncture below L3 avoids the cord).[1]

The classic cord syndromes, each a distinct lesion pattern:

• Complete cord transection - loss of everything (motor, sensory, autonomic) below the level, with initial spinal shock (flaccidity, areflexia) then spasticity.
• Anterior spinal artery syndrome - motor and pain/temperature lost bilaterally, dorsal columns spared (vibration and proprioception intact); usually vascular (aortic surgery, dissection, hypotension).
• Brown-Sequard (hemicord) syndrome - ipsilateral motor (corticospinal) and proprioception (dorsal columns) loss, contralateral pain and temperature loss (spinothalamic); the textbook lesion of a stab wound or hemitumour.
• Central cord syndrome - the commonest incomplete cord injury; weakness greater in the arms than the legs (the arm fibres lie centrally in the corticospinal tract), with variable sensory loss and bladder dysfunction; typically a hyperextension injury in an older patient with cervical spondylosis.
• Posterior cord syndrome - rare; isolated loss of proprioception and vibration (the dorsal columns), as in B12 deficiency (subacute combined degeneration) or tabes dorsalis. [1]

The blood-brain barrier

The blood-brain barrier (BBB) is the specialised interface that strictly limits what crosses from the blood into the brain extracellular fluid. Its structural basis is the tight junctions (zonulae occludentes) between the cerebral capillary endothelial cells - these seal the paracellular space and force solutes to cross the cells themselves. The endothelium is invested by a basement membrane, by pericytes (contractile cells that regulate flow and permeability), and by the astrocyte end-feet that ensheath over 99 per cent of the capillary surface. It is the tight junction, not the astrocyte, that is the barrier itself - but the astrocytes induce and maintain it.[1]

What crosses and what does not:

• Crosses freely: gases (oxygen, carbon dioxide), water, small lipophilic molecules (most anaesthetic agents, ethanol, barbiturates), and substances carried by specific transporters - glucose (GLUT1), amino acids (L-type for large neutral amino acids such as L-DOPA, the basis of Parkinson therapy since dopamine itself does not cross).
• Excluded: large, polar, or charged molecules; plasma proteins; most drugs that are highly protein-bound; many antibiotics (penicillin enters poorly and is concentrated only when the meninges are inflamed). [1]

A handful of circumventricular organs sit outside the barrier - the area postrema (the chemoreceptor trigger zone that initiates vomiting, e.g. to opioids and digoxin), the organum vasculosum of the lamina terminalis (the osmoreceptor), the subfornical organ, the median eminence and posterior pituitary (for hormone release into blood), and the pineal gland. These need to sample the blood directly, so their capillaries are fenestrated.[1]

Clinically, the BBB matters in three ways: (1) drug delivery - you must design a drug to cross it (levodopa for Parkinson, prodrugs such as enalapril, or bypass it by intrathecal injection of, say, baclofen or methotrexate); (2) meningeal inflammation opens the barrier, which is why penicillin reaches therapeutic CSF levels in bacterial meningitis but not in health, and why gadolinium contrast enhances an abscess or tumour ring; and (3) breakdown underlies cerebral oedema in infection, tumour, ischaemia and trauma - the vasogenic oedema that raises intracranial pressure. [1]

The autonomic nervous system

The autonomic nervous system (ANS) is the involuntary motor division that controls smooth muscle, cardiac muscle and glands. It has three parts: the sympathetic (thoracolumbar), the parasympathetic (craniosacral), and the enteric (the intrinsic plexuses of the gut).[1]

The sympathetic outflow is thoracolumbar - the preganglionic neurons lie in the lateral horn of the spinal cord from T1 to L2/L3. Their fibres exit via the ventral roots, enter the sympathetic chain (paravertebral ganglia) via the white ramus communicans, and there either synapse (at the same level, a higher level, or a lower level) or pass straight through to a prevertebral (collateral) ganglion (the coeliac, superior mesenteric and inferior mesenteric). The result is the classic "fight or flight" response: tachycardia, increased contractility, bronchodilation, pupillary dilation, sweating, piloerection, splanchnic vasoconstriction, hepatic glycogenolysis and adrenal medullary secretion. The preganglionic fibre is short (it synapses close to the cord), the postganglionic fibre is long (it travels to the target). The adrenal medulla is a modified sympathetic ganglion: it is driven directly by preganglionic fibres and secretes adrenaline (~80%) and noradrenaline (~20%) directly into the blood.[1]

The parasympathetic outflow is craniosacral. The cranial part travels in CN III (the Edinger-Westphal pupillary constrictor), CN VII (lacrimal and submandibular/sublingual salivary), CN IX (parotid) and the mighty CN X (vagus), which supplies the heart, the airways and most of the gut down to the splenic flexure. The sacral part arises from S2-S4 (the pelvic splanchnic nerves) and supplies the distal colon, bladder and the pelvic viscera. The preganglionic fibre is long (it runs all the way to a ganglion in or near the target organ) and the postganglionic fibre is short.[1]

The receptor pharmacology is the bridge to the drugs the intensivist uses every day. Alpha-1 (Gq-coupled) causes vasoconstriction, mydriasis, prostatic contraction - phenylephrine, noradrenaline. Alpha-2 (Gi-coupled, presynaptic) inhibits further noradrenaline release - clonidine, dexmedetomidine. Beta-1 (Gs-coupled) increases heart rate and contractility and renin release - isoprenaline, dobutamine. Beta-2 (Gs-coupled) bronchodilates, uterine-relaxes and shifts potassium into cells - salbutamol. The muscarinic receptors (M2 slows the heart, M3 contracts the bladder and gut and bronchoconstricts) are the targets of atropine (antagonist) and neostigmine (indirect, via acetylcholinesterase inhibition). The enteric nervous system - the myenteric (Auerbach) plexus between the longitudinal and circular muscle and the submucosal (Meissner) plexus in the submucosa - is the brain of the gut, capable of peristalsis even when denervated; the vagus and the splanchnic sympathetic fibres merely modulate it.[1]

[1]

Exam practice — SAQs

[1] [1]

Clinical pearls

Evidence and trials

[1] [2] [3] [4] [6] [5]

Red flags

References

1. [1]National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group Tissue plasminogen activator for acute ischemic stroke N Engl J Med, 1995.PMID 7477192
2. [2]Hacke W, Kaste M, Bluhmki E, et al (ECASS Investigators) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke N Engl J Med, 2008.PMID 18815396
3. [3]Nogueira RG, Jadhav AP, Haussen DC, et al (DAWN Investigators) Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct N Engl J Med, 2018.PMID 29129157
4. [4]Albers GW, Marks MP, Kemp S, et al (DEFUSE 3 Investigators) Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging N Engl J Med, 2018.PMID 29364767
5. [5]Wijdicks EF, Varelas PN, Gronseth GS, Greer DM (American Academy of Neurology) Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology, 2010.PMID 20530327
6. [6]Molyneux A, Kerr R, Stratton I, et al (ISAT Collaborative Group) International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial Lancet, 2002.PMID 12414200