Meningeal Haemorrhage

Anatomical Background

• Extradural space - between the inner skull and dura mater
• Subdural space - between the dura and arachnoid mater
• Subarachnoid space - between the arachnoid and pia mater (normally filled with CSF)

1. Extradural (Epidural) Haemorrhage

Definition and Frequency

Mechanism and Source

• Almost always traumatic and strongly associated with skull fracture (except in infants/children, where the dura is more firmly adherent)
• Classical cause: rupture of the middle meningeal artery, most often its anterior branch, at the point it exits the bony canal at the pterion (temporal bone)
• Can also arise from posterior branch of the middle meningeal artery, anterior meningeal vessels (fracture of anterior fossa), internal maxillary artery, or dural venous sinuses
• Acute epidural haemorrhage: arterial in origin (middle meningeal artery rupture)
• Subacute epidural haemorrhage: from torn dural sinuses, middle meningeal veins, or diploic veins; symptoms appear 3+ days after injury
• High-pressure arterial blood progressively strips the dura from the skull, accumulating a haematoma. A minimum of ~35 ml is needed before clinical signs appear, though 100 ml is typically associated with fatalities

Classic Clinical Course (Lucid Interval)

1. Initial concussion - loss of consciousness immediately after trauma
2. Lucid interval - patient regains consciousness; the dura is slowly stripped by accumulating blood, but ICP remains normal as CSF is displaced into the spinal canal
3. Confusion and irritability as ICP rises
4. Deteriorating consciousness progressing to coma
5. Contralateral motor signs: twitching then paralysis progressing face → arm → leg (as clot spreads over motor cortex from below upwards)
6. Ipsilateral pupil: initially constricts then dilates (3rd nerve compression from uncal herniation through tentorial hiatus)
7. Eventually bilateral fixed dilated pupils and decerebrate rigidity (midbrain cone)

Note: The classical lucid interval picture is actually not common in acute cases. The more frequent presentation is severe head injury with skull fracture and stupor progressing to deep coma.

Localising the Side

• Side of skull fracture
• Boggy swelling beneath the temporal muscle (ipsilateral)
• Side of initial pupil dilatation

Key Features - S Das, Manual on Clinical Surgery:

• Supratentorial haemorrhage causes uncal herniation through the tentorial hiatus → midbrain compression
• Infratentorial haemorrhage (far less common): elevated BP, slow pulse, irregular respiration, ataxia, nystagmus, lower cranial nerve palsies

Medicolegal Significance

1. Good prognosis with prompt surgical drainage (burr hole or craniotomy), but a contralateral haematoma must always be excluded
2. Patient may be discharged during the lucid interval and die at home - risk of medical negligence charge
3. Clinical picture may resemble drunkenness, leading to missed diagnosis (patient may die in police custody)
4. Heat haematoma - a forensic artefact that mimics extradural haemorrhage: blood extruded from diploe/venous sinuses into extradural space during fire; honeycombed, brown, friable, pink due to high carboxyhaemoglobin; distinguishable by comparing COHb levels in haematoma vs peripheral blood

2. Subdural Haemorrhage

Definition and Frequency

Mechanism and Source

• Results from rapid deceleration of the head, tearing bridging (communicating) veins that connect cortical veins to the dural venous sinuses (especially the superior sagittal sinus)
• These thin, unsupported veins traverse both the subarachnoid and subdural spaces and are particularly vulnerable to rotational movement
• Less often due to cortical vein laceration or injury to dural sinuses
• Not necessarily associated with skull fracture
• Blood accumulates at lower venous pressure than in EDH, so onset is slower

Location

Classification

• Occurs in elderly and chronic alcoholics with cerebral atrophy - the brain can oscillate within the now-oversized skull, stretching bridging veins
• Often follows trivial or forgotten trauma
• Symptoms: mild confusion, forgetfulness, emotional disorder - easily misdiagnosed as schizophrenia (in young) or dementia (in elderly)
• The haematoma does not resolve because the subdural space lacks mesothelial lining; it becomes encased by inner and outer fibrous membranes
• Susceptible to re-expansion by recurrent bleeding (membrane vessels are thin and poorly endothelialised) and osmotic fluid absorption
• Unsuspected chronic subdural haematoma is a known cause of sudden unexplained death in alcoholics

Gross Appearance by Age

Histological Dating (Dikshit's Forensic Medicine)

3. Subarachnoid Haemorrhage (SAH)

Definition

Causes

1. Rupture of a berry (saccular) aneurysm - most common non-traumatic cause; aneurysms typically occur at bifurcations of the Circle of Willis or its major branches, due to developmental defects in the vessel media
2. Arteriosclerotic changes in vessel media, associated with hypertension (in older persons)
3. Leaking intracerebral haemorrhage
4. Disease states: purpuric states, leukaemia, angioma

1. Cerebral contusions or lacerations
2. Explosive blast
3. Asphyxia by strangulation
4. Traumatic asphyxia
5. Damage to vertebral arteries (e.g., fracture of upper cervical vertebrae, blows to the neck)
6. Prolonged hyperextension of the head (e.g., during bronchoscopy - may result in SAH over the base of the brain, raising concern for malpractice)

Comparison: Extradural vs. Subdural Haemorrhage

Treatment

• Extradural haemorrhage: Surgical emergency - burr hole or craniotomy for evacuation. Must always exclude a contralateral haematoma.
• Subdural haemorrhage: Surgical drainage for symptomatic acute/subacute cases; chronic SDH may be managed conservatively or with burr hole drainage.
• Subarachnoid haemorrhage: Supportive management, aneurysm clipping or coiling for berry aneurysm rupture, nimodipine to prevent vasospasm.

Space-Occupying Lesions (SOL) Within the Skull

The Monro-Kellie Doctrine

1. Brain tissue (~80%)
2. Blood (~10%)
3. CSF (~10%)

Classification of Intracranial SOLs

1. Neoplasms (Tumours)

Primary Brain Tumours

Secondary (Metastatic) Tumours

• Lung (most common), Breast, Melanoma, Renal cell carcinoma, Colorectal cancer

2. Haematomas

3. Cerebral Abscess

• Direct spread from frontal sinusitis, otitis media/mastoiditis, dental infections
• Haematogenous spread (infective endocarditis, pulmonary AVM)
• Post-traumatic (compound skull fractures)

4. Other SOLs

• Chronic subdural haematoma (can behave as a slow-growing mass)
• Cerebral oedema (diffuse or focal)
• Hydrocephalus (increased CSF volume with ventricular enlargement)
• Arachnoid cysts
• Parasitic cysts (e.g., neurocysticercosis)

Clinical Features

(a) Focal/Localising Symptoms

• Epileptic fits arising for the first time in an adult should always be suspected as tumour until proven otherwise; hallucinations of taste/smell suggest uncinate process involvement
• Twitching/paresis starting in both feet spreading to one side: parasagittal meningioma of the opposite side
• Incoordination ipsilateral to tumour + nystagmus: cerebellar hemisphere tumour
• Personality change, memory loss, poor concentration: frontal lobe tumour
• Progressive focal deficit (as opposed to sudden vascular onset) is highly suggestive of tumour

(b) Symptoms of Raised ICP

• Midline and posterior fossa tumours: symptoms appear earliest (they partially obstruct CSF outflow causing internal hydrocephalus)
• Temporal and parietal lobe tumours: moderate delay
• Frontal lobe tumours: symptoms appear latest (push ventricles back rather than obstructing them)

1. Headache - the most constant symptom; classically worst in the early morning on getting out of bed and on coughing/straining (raised hydrostatic pressure); occipital headache radiating down the neck = subtentorial growth; bitemporal headache = pituitary tumour; unilateral headache = ipsilateral tumour
2. Vomiting - projectile, usually morning, before breakfast, not preceded by nausea; aggravated by coughing and straining
3. Dimness of vision / papilloedema - optic disc swelling with blurred margins on fundoscopy; occurs early in subtentorial and inferior frontal/temporal tumours
4. Bradycardia - due to raised ICP (Cushing's reflex - also includes hypertension and irregular respirations)
5. Diplopia - from VIth nerve (abducent) palsy, a "false localising sign" as it is stretched over the petrous ridge with raised ICP
6. Drowsiness and slowed mentation

In infants (before skull suture fusion): raised ICP presents with increasing head circumference, prominent scalp veins, bulging fontanelle, and sunsetting sign (loss of upgaze = Parinaud's syndrome). - Bailey & Love's

(c) Symptoms of Cone (Herniation) Formation

1. Drowsiness progressing to coma
2. Slow pulse rate
3. Neck stiffness
4. Paroxysmal (plateau) headache
5. Pupillary dilatation (ipsilateral - from 3rd nerve compression)

Herniation Syndromes

1. Subfalcine (Cingulate) Herniation

• Unilateral/asymmetric hemisphere expansion pushes the cingulate gyrus under the falx cerebri
• Can compress the anterior cerebral artery (ACA), causing medial frontal/parietal infarcts

2. Transtentorial (Uncal) Herniation

• Medial temporal lobe (uncus) is compressed against the free margin of the tentorium cerebelli
• Compresses CN III → ipsilateral pupil dilation, ptosis, ophthalmoplegia
• Compresses posterior cerebral artery (PCA) → contralateral homonymous hemianopia
• With large herniation, the contralateral cerebral peduncle is compressed against the opposite tentorial edge → Kernohan's notch phenomenon (ipsilateral hemiparesis - a "false localising sign")
• Duret haemorrhages: secondary flame-shaped midline/paramedian brainstem bleeds from distortion/tearing of penetrating vessels supplying the upper brainstem; indicate severe, often fatal herniation

3. Tonsillar Herniation

• Cerebellar tonsils are displaced downward through the foramen magnum
• Life-threatening - compresses the medullary respiratory and cardiac centres
• Results in bradycardia, respiratory arrest, and death

Investigation

Management

Immediate/Emergency

1. Airway and ventilation - controlled hyperventilation lowers PaCO₂ → cerebral vasoconstriction → reduces ICP acutely
2. Head elevation to 30° - reduces hydrostatic pressure at cranial vault
3. Mannitol 0.5-1 g/kg IV - osmotic diuresis draws free water from brain; effect delayed ~20 minutes; lasts 4-6 hours
4. Hypertonic saline - alternative osmotherapy
5. Emergency CT + neurosurgical referral

Specific

Anticonvulsants are used for seizure management but prophylactic anticonvulsants are not recommended in brain tumour patients without prior seizures. - Bailey & Love's

Key Points Summary

• A chronic SOL produces symptoms after a silent growth phase, appearing first as focal/localising signs, then raised ICP symptoms, and finally herniation signs
• The triad of brain tumour presentation: raised ICP + seizures + focal neurological deficit
• Epilepsy of new onset in an adult must be treated as tumour until excluded
• Lumbar puncture is contraindicated until SOL is excluded by imaging
• Herniation (coning) is the final common pathway to death: subfalcine → transtentorial → tonsillar
• Metastases are the most common intracranial tumours overall; lung and breast are the most frequent primaries

Note on Sources: Snell's Clinical Neuroanatomy is not available in this textbook library. The explanation below draws from the three most authoritative equivalents available: Histology: A Text and Atlas (Ross & Pawlina, 8th Ed.), Neuroscience: Exploring the Brain (Bear, Connors & Paradiso, 5th Ed.), and Medical Physiology (Boron & Boulpaep). The content closely parallels Snell's own coverage of these topics.

Neurons and Neuroglia

Part I: The Neuron

Definition and Overview

Neuron Doctrine

Structure of the Neuron

1. Cell Body (Soma / Perikaryon)

• Microtubules (25 nm diameter): composed of tubulin dimers; serve as tracks for axonal transport (kinesin for anterograde, dynein for retrograde)
• Neurofilaments (10 nm): intermediate filaments unique to neurons; provide structural support and regulate axon calibre; accumulation seen in Alzheimer's disease (neurofibrillary tangles of hyperphosphorylated tau)
• Microfilaments / actin filaments (8 nm): anchored to the inner membrane; regulate synaptic structure and dendritic spine morphology

2. Dendrites

• Most neurons have many dendrites, which dramatically increase the receptive surface area
• Contain dendritic spines - small protrusions that form the postsynaptic site of the majority of excitatory synapses
• Dendritic spines contain a postsynaptic density with clusters of neurotransmitter receptors (mainly glutamate receptors for fast excitatory transmission), voltage-gated Na⁺ and K⁺ channels, and an actin cytoskeleton
• Unlike axons, dendrites can contain polyribosomes (allowing local protein synthesis near synapses, critical for synaptic plasticity)
• Dendritic spine morphology is crucial for learning and memory; abnormal spines (long, thin, immature) are associated with intellectual disability and autism - Neuroscience: Exploring the Brain

3. Axon

• Each neuron has only one axon (but may have many collateral branches)
• Begins at the axon hillock, which tapers into the initial segment - the site where action potentials are initiated (highest concentration of voltage-gated Na⁺ channels)
• No rough ER in the axon; proteins must be synthesised in the cell body and transported down
• Membrane composition is fundamentally different from the soma membrane
• Terminates in axon terminals (boutons terminaux / synaptic knobs) which form synapses with the next neuron or effector cell
• Axonal Transport:
  • Anterograde (soma → terminal): Kinesin motors carry vesicles, organelles, and newly synthesised proteins down the axon
  • Retrograde (terminal → soma): Dynein motors return used membrane, organelles, and trophic signals back; this pathway is exploited by herpes virus and tetanus toxin to reach the CNS

4. Synapse

Classification of Neurons

A. By Number of Processes (Morphological)

B. By Function

C. By Axon Length

• Golgi Type I (Projection neurons): Long axons extending to distant brain regions (e.g., pyramidal cells)
• Golgi Type II (Local circuit neurons): Short axons that do not extend beyond the local area (e.g., cortical stellate cells)

Impulse Conduction

1. Voltage-gated Na⁺ channels at the initial segment open → Na⁺ influx → depolarisation (resting potential of -70 mV rises to +30 mV)
2. Na⁺ channels inactivate; voltage-gated K⁺ channels open → K⁺ efflux → repolarisation
3. Local current flows to adjacent membrane, propagating the action potential

• Myelin acts as an insulator; voltage reversal (depolarisation) can only occur at the nodes of Ranvier (gaps in the myelin sheath with high densities of voltage-gated channels)
• The impulse "jumps" from node to node - this is saltatory conduction (Latin: saltus = to jump)
• Saltatory conduction is much faster than continuous conduction in unmyelinated fibres
• Conduction velocity increases with axon diameter and myelin thickness

Part II: Neuroglia (Glial Cells)

Only the nuclei of glial cells are visible in routine H&E-stained sections. Special heavy metal staining (e.g., gold sublimate) or immunocytochemistry (e.g., anti-GFAP for astrocytes) is required to visualise the full cell shape. - Histology: A Text and Atlas

Distribution of All Glial Cell Types in Brain

Central Neuroglia (CNS)

1. Astrocytes

1. Structural scaffolding: During development, radial glial cells (derived from astrocytes) guide neuronal migration; some astrocytes span the entire brain thickness
2. Blood-brain barrier (BBB) maintenance: Astrocyte endfeet (perivascular feet) wrap around all brain capillaries and are integral to the tight junctions forming the BBB; regulate glucose uptake, store it as glycogen, and supply neurons with lactate
3. Potassium spatial buffering: Astrocyte membranes have abundant K⁺ pumps and channels; they absorb excess extracellular K⁺ released during neural activity, maintaining the microenvironment and preventing excessive neuronal excitability
4. Neurotransmitter regulation: Astrocytes take up and remove excess glutamate and other neurotransmitters from synaptic clefts; confine neurotransmitters to the synaptic space
5. Synapse formation and pruning: Signal neurons to initiate synapse growth (during development) and actively phagocytose excess synapses (synaptic pruning) to establish precise neural circuitry
6. Glia limitans: Protoplasmic astrocytes extend subpial feet to the pia mater, forming the glia limitans - a relatively impermeable barrier surrounding the CNS
7. Reactive gliosis: After injury, astrocytes proliferate and form a glial scar that walls off the damaged area but also impedes axonal regeneration
8. Phagocytosis: Reactive astrocytes can phagocytose myelin debris when microglia are overwhelmed

Tumours from fibrous astrocytes = Astrocytomas - account for ~80% of adult primary brain tumours; GFAP-positive on immunostaining. - Histology: A Text and Atlas

2. Oligodendrocytes

• Each oligodendrocyte gives off several tongue-like processes; each process wraps itself around a segment of a nearby axon, forming one internode of myelin
• A single oligodendrocyte can myelinate up to 40 different axons simultaneously (unlike Schwann cells, which myelinate only one axon segment each)
• The nucleus-containing cell body may be at some distance from the axons it myelinates

• CNS myelin: Proteolipid protein (PLP), Myelin oligodendrocyte glycoprotein (MOG), Oligodendrocyte myelin glycoprotein (OMgp)
• PNS myelin: P0, PMP22 (expressed by Schwann cells)

3. Microglia

• Phagocytosis: Primary phagocytic cells of the brain; remove cellular debris, dead neurons, pathogens, and excess synapses
• Immune surveillance: Constantly survey the brain parenchyma with motile processes; activated by injury, infection, or disease
• Antigen presentation: Can present antigens during CNS inflammation
• Neuroprotection and neurotoxicity: Can be neuroprotective (clearing debris) or contribute to neuronal damage if chronically activated

4. Ependymal Cells

• Single layer of cells; lack an external lamina (unlike true epithelia)
• Apical surface: cilia (for CSF circulation) + microvilli (for CSF absorption)
• Bound by junctional complexes at their apical surfaces
• Basal surface: numerous infoldings that interdigitate with adjacent astrocyte processes

• Choroid plexus cells: Modified ependymal cells associated with capillary loops; responsible for producing CSF by active transport and secretion
• Tanycytes: Specialised ependymal cells in the floor of the third ventricle; lack cilia; have a long basal process projecting into brain parenchyma; involved in transporting substances between CSF and hypothalamic portal circulation; sensitive to glucose levels (possible role in energy balance regulation)

Peripheral Neuroglia (PNS)

5. Schwann Cells

6. Satellite Cells

• Surround neuronal cell bodies in peripheral ganglia (analogous to astrocytes in the CNS)
• Provide metabolic support and regulate the microenvironment around ganglion cells

7. Other Peripheral Neuroglia

• Terminal (perisynaptic) Schwann cells (teloglia): Cover axon terminals at the neuromuscular junction; regulate synaptic transmission
• Enteric glial cells: Associated with ganglia in the wall of the alimentary canal (enteric nervous system)
• Müller cells: Radial glial cells of the retina; support retinal neurons and photoreceptors

Summary Comparison Table

Neuron vs. Nerve

The Neuron - The Individual Cell

• Cell body (soma/perikaryon) - contains the nucleus and organelles
• Dendrites - multiple branching processes that receive incoming signals
• Axon - a single long process that transmits impulses away from the cell body
• Synaptic terminals - where the neuron communicates with the next cell

"A peripheral nerve is a bundle of nerve fibers held together by connective tissue." - Histology: A Text and Atlas (Ross & Pawlina)

The Nerve - A Bundle of Axons

Structure of a Peripheral Nerve

Key Differences at a Glance

An Analogy

• Each individual wire inside the cable = one axon (part of one neuron)
• The rubber insulation around each wire = myelin sheath + endoneurium
• Each sub-bundle of wires = a fascicle (surrounded by perineurium)
• The outer plastic jacket of the whole cable = epineurium
• The neuron itself = the wire + the power source (the cell body back at the wall) combined

One Important Note

• Inside the CNS (e.g., anterior horn motor neurons, brainstem nuclei), or
• In peripheral ganglia (e.g., dorsal root ganglia for sensory neurons, autonomic ganglia for postganglionic autonomic neurons)