Case 1 – Space-Occupying Lesion

Anatomy and Physiology:

Cerebral Circulation:

 Two paired arteries are responsible for blood supply to the brain:
 Internal carotid arteries
 Vertebral arteries
 These arteries arise in the neck and form an anastomotic circle in the cranium known as the Circle
of Willis.
 Branches from this circle supply most of the cerebrum.
 Internal carotid arteries:
 Originate at the bifurcation of the left and right common carotid arteries at the level of
C4.
 Move superiorly through the carotid sheath and enter the brain through the carotid canal.
 After passing through the cavernous sinus, they give rise to the ophthalmic, posterior
communicating, anterior choroidal and anterior cerebral arteries.
 Vertebral arteries:
 Originate from the
subclavian arteries and
ascend through the
transverse foramina of the
cervical vertebrae.
 They enter the cranial
cavity via the foramen
magnum and give off
meningeal branches along
with the anterior and
posterior spinal arteries,
and the posterior inferior
cerebellar arteries.
 After this, the two
vertebral arteries
converge to form the
basilar artery, supplying
the cerebellum and pons,
before terminating when
it bifurcates into the
posterior cerebral arteries.
 The three main arteries that supply the cerebral hemispheres are the anterior, middle and posterior
cerebral arteries, which all arise from the Circle of Willis.
 The posterior inferior cerebellar arteries originate from the vertebral arteries to supply the
cerebellum, along with the anterior inferior cerebellar and superior cerebellar arteries, which
originate from the basilar artery.
Lateralisation and Localisation of Cortical Function:

 Lateralisation:
 There is a tendency for some functions to be lateralised to the left or right hemisphere,
resulting in hemispheric specialisation.
 There are asymmetries in brain function, which means that some functions can be
processed mainly within one hemisphere, eliminating delays caused by long callosal
transmission times.

Functions of Dominant Hemisphere Function of Nondominant Hemisphere

(Usually Left) (Usually Right)
Language Prosody – emotion conveyed by tone of
voice
Praxis – skilled motor formulation Visual-spatial analysis
Arithmetic – sequential and analytical Arithmetic – ability to estimate
calculating skills
Musical ability – analytical skills in trained Musical ability – skill in untrained musicians
musicians or for complex pieces played by trained
musicians
Sense of direction – following a sequence of Sense of direction – finding the way through
instructions spatial awareness

 Localisation:
 Primary Motor Cortex – Brodmann Area 4
 The primary motor cortex confers voluntary control over the movement produced
by skeletal muscles.
 The cortex on each side of the brain controls muscles on the opposite side of the
body.
 Supplementary Motor Area – Brodmann Area 6
 Lies on the medial surface of each hemisphere, anterior to the primary motor
cortex.
 Plays a role in programming complex sequences of movement.
 Premotor Cortex – Brodmann Area 6
 Located on the lateral surface of each hemisphere, anterior to the primary motor
cortex.
 Important in orienting the body and arms toward a specific target.
 Primary Somatosensory Cortex – Brodmann Areas 3, 1 and 2
 Site for initial cortical processing and perception of both somesthetic and
proprioceptive input.
 The cortex on each side of the brain receives sensory input from the opposite side
of the body.
 The awareness of touch, pressure, temperature or pain is detected at a lower level
by the thalamus, but the somatosensory cortex provides the level of intensity of
the stimulus along with spatial discrimination.
 Primary Visual Cortex – Brodmann Area 17
 The primary visual cortex receives visual signals from the eyes via the optic
nerve and associated pathways.
  Broca’s Area – Brodmann Areas 44 and 45
 Region of the brain associated with speech production.
 Damage to this area results in expressive aphasia.
 Wernicke’s Area – Brodmann Area 22
 Region of the brain associated with understanding of written and spoken
language.
 Damage to this area results in receptive aphasia.
 Connected to Broca’s area via the arcuate fasciculus, which can also be damaged
and cause conductive aphasia.

Meninges:
Central Nervous System Glial Cells:
1. Astrocytes
 Biochemical support of endothelial cells that line the blood-brain barrier.
 Maintenance of extracellular ion concentration.
 Provide structure to neurons and play a role in repair and scarring following traumatic
injury.
2. Oligodendrocytes
 Provide support and insulation for axons by creating the myelin sheath.
3. Ependymal cells
 Neuroepithelial cells which line the ventricles of the brain and central canal of the spinal
cord.
 Play an important role in the production and regulation of CSF.
4. Microglia
 Resident macrophage cells, which act as the first and main form of CNS immune
defence.
 Important for brain maintenance as they scavenge for plaque, damaged neurons or
synapses, and infectious agents.
Cerebrospinal Fluid and Ventricles:

 Modified fenestrated ependymal cells form choroid plexuses within the ventricles and produce
CSF.
 The apical surfaces of ependymal cells have cilia to assist in the circulation of CSF and microvilli
for absorption.
 Most CSF is reabsorbed via arachnoid granulations into the dural sinuses.
 Choroid plexuses are found in the lesser curve of the lateral ventricles, the roof of the third
ventricle, and in the fourth ventricle.
 CSF production is regulated by cerebral perfusion pressure.
𝐶𝑒𝑟𝑒𝑏𝑟𝑎𝑙 𝑃𝑒𝑟𝑓𝑢𝑠𝑖𝑜𝑛 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 = 𝑀𝑒𝑎𝑛 𝐴𝑟𝑡𝑒𝑟𝑖𝑎𝑙 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 − 𝐼𝑛𝑡𝑟𝑎𝑐𝑟𝑎𝑛𝑖𝑎𝑙 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒
Visual Fields:

 Information passes from the eyes through the optic nerve and optic chiasm into the optic tract.
 Information from the left visual field is transmitted to the right side of the thalamus,
while information from the right visual field is transmitted to the left side of the thalamus.
 Most of the information is relayed to the lateral geniculate nucleus of the thalamus, which then
sends out optic radiations.
 Meyer’s loop
 Inferior tract which passes through the temporal lobe before synapsing at the
primary visual cortex, carrying information from the superior vision field.
 Baum’s loop
 Superior tract which passes through the parietal lobe before synapsing at the
primary visual cortex, carrying information from the inferior vision field.
Pathology and Pathophysiology:
Brain Tumours:

 A brain tumour is defined as any mass or growth that occurs within the cranium, including the
brain itself, cranial nerves, meninges, bone and glands.
 Primary CNS tumours:
 Arise from abnormal proliferation of cells originating in the CNS.
 Metastatic tumours:
 Arise from neoplasms elsewhere in the body, which spread to the brain.
 The symptoms of a brain tumour depend on its location, size and rate of growth.
 Pathogenesis:
 Proto-oncogenes
 Normal genes involved in mitosis.
 Encode various growth factors, receptor kinases, signal transduction molecules
and DNA transcription regulators.
 Mutation leads to gain of function as it becomes an oncogene and promotes
excessive cell growth, division, vascularisation and loss of adhesion.
 Tumour-suppression genes
 Genes that control the cell cycle and response to DNA damage along with
apoptosis.
 Mutation leads to loss of function as there is an increased risk of uncontrolled
cell growth and division.
 p53
 p53 is a specific tumour suppression gene which signals arrest of the cell cycle
and apoptosis when DNA damage is detected.
 Mutation of this gene increases risk of proliferating damaged cells.
 World Health Organisation Classification:
WHO Classification: Description:
Grade 1 Lesions with low proliferative potential that are non-malignant and
Well differentiated have the possibility of being cured following surgical resection alone
Grade 2 Lesions that are generally infiltrating and have low mitotic activity
Moderately differentiated but recur more frequently
Grade 3 Lesions have histological evidence of active malignancy and
Poorly differentiated anaplasia, and are treated with aggressive adjuvant therapy
Grade 4 Lesions that are mitotically active, necrosis-prone and generally
Undifferentiated associated with rapid progression and fatal outcomes

1. Gliomas
 Astrocytoma – Predominant cell type is an astrocyte
 Account for 80% of adult gliomas and are usually found in the cerebral
hemispheres.
 Grade 1 – Pilocytic astrocytoma – Relatively benign and usually affects children,
with the most common location in the cerebellum
 Grade 2 – Diffuse astrocytoma
 Grade 3 – Anaplastic astrocytoma
 Grade 4 – Glioblastoma
  Oligodendroglioma – Predominant cell type is an oligodendrocyte
 Account for 5-15% of adult gliomas and are usually found in the frontal or
temporal lobes.
 Grade 2 – Well-differentiated oligodendroglioma
 Grade 3 – Anaplastic oligodendroglioma
 Ependymoma – Predominant cell type is an ependymal cell
 Tumour usually arises in the ventricular system near the fourth ventricle.
2. Neuronal cell tumours
 Usually contain neuronal and glial elements.
 Slow growing until glial portion becomes anaplastic.
 Usually present with seizures.
3. Meningiomas
 Predominantly benign tumours which arise from arachnoid meningothelial cells.
 Usually present with vague non-localised symptoms or focal findings referrable to a
compression of the adjacent brain.
4. Primary CNS lymphomas
 Most common CNS neoplasm in immunocompromised individuals.
 Often multifocal within brain.
5. Medulloblastomas
 Occurs predominantly in children and exclusively within the cerebellum.
 Neuronal and glial markers are nearly always expressed, and the tumour is highly
malignant.
6. Pituitary adenomas
 Tumour compressing the pituitary gland, which can lead to endocrine disturbances.
 Can also compress the optic chiasm, leading to bitemporal hemianopia.
 Pathophysiology:
 Tumours can invade, infiltrate and supplant normal parenchymal brain tissue, disrupting
normal function and damaging neural areas and pathways.
 Tumours can also cause obstructive hydrocephalus if they block the cerebral aqueduct
between the third and fourth ventricle, or disrupt the blood-brain barrier by promoting
angiogenesis.
 Depending on the location of the lesion, there will be direct effects due to destruction of
the brain area, along with complications caused by raised ICP and herniation.
 Brain tumours can also cause seizures by destroying small GABAergic neurons, reducing
levels of cortical inhibition and causing hyperexcitability of pyramidal cells.
Seizures:

 Seizures are paroxysmal changes in neurological function due to abnormal electrical activity in
cortical neurons.
 During a seizure, a large group of neurons are activated in a repetitive, unrestricted and
hypersynchronous fashion as synaptic inhibition fails.
 Anyone can experience a seizure under the appropriate pathophysiological conditions, however
Epilepsy refers to an enduring alteration of brain function which facilitates recurrent seizures.
 Focal seizures:
 Simple
 Only one part of the cerebrum is affected so there is no loss or change in
consciousness.
 Symptoms are dependent on the area affected – Can be motor, sensory,
autonomic or psychiatric.
 No post-ictal consciousness impairment, however there can be motor
impairment.
 Complex
 Begins with one part of the cerebrum affected, but there is a spread of discharge
leading to altered consciousness.
 There is usually an olfactory or visual aura.
 Commonly associated with post-ictal confusion, disorientation, fatigue or
agitation.
 Secondary generalisation can occur if there is a sufficient spread in discharge.
 Generalised seizures:
 Tonic-Clonic
 Has a prodrome for hours to days before seizure, including unease or irritability.
 Tonic ictal phase involves muscle rigidity.
 Clonic ictal phase involves repetitive jerking of face and limbs, with frothing
and incontinence.
 In the post-ictal phase, the patient will have flaccid limbs, an extensor plantar
reflex, confusion and aching muscles.
 Myoclonic
 Sudden generalised single body jerk, which can occur in clusters.
 Clonic
 Repetitive rhythmic jerking movements.
 Tonic
 Rigid muscle flexion or extension for a period time.
 Atonic
 Sudden loss of postural tone, leading to a collapse.
 Often causes injury and can be mixed with other seizure types.
 Absence
 Sudden loss of consciousness with preserved postural tone.
 Minimal motor manifestations.
 Typically lasts 15 seconds with no post-ictal phase.
Raised Intracranial Pressure:

 The cranial vault is a fixed space containing brain tissue, blood and CSF, none of which are
compressible.
 Normally, ICP is fairly stable at around 5-15mmHg and ICP requires intervention once it is raised
above 20mmHg.
 A space-occupying lesion can be accommodated for by decreasing CSF production, however if it
grows then this compensation begins to fail.
 Causes of raised ICP:
 Space-occupying lesion
 Brain tumour
 Brain abscess
 Intracranial haemorrhage
 Hydrocephalus
 Obstruction in CSF flow
 Choroid plexus malfunction
 Cerebral oedema
 Head trauma
 Stroke
 Metabolic disorders
 Hypoglycaemia
 Headache:
 Pain receptors are located at the base of the brain in certain structures (not brain
parenchyma)
 Arteries and veins in the meninges and dural folds
 Extracranial vessels and cranial nerves
 Scalp, neck and facial muscles
 Paranasal sinuses, eyes and teeth
 Headaches often arise from irritation of the blood vessels and meninges, being
transmitted via the trigeminal nerve.
 Headaches associated with raised ICP are usually worse in the morning and on coughing,
straining or performing the Valsalva manoeuvre.
 Lying supine causes build up on venous blood in the brain due to gravity,
resulting in cerebral oedema and further increased ICP, worsening the headache
in the morning.
 There is also respiratory depression during sleep, and the build-up of CO2
causes vasodilation of cerebral blood vessels, resulting in blood building up
within the cranial vault, increasing ICP and worsening the headache in the
morning.
 Coughing or straining increases intra-thoracic pressure, reducing drainage from
the jugular vein, which causes a transient increase in blood volume within the
cranium, increasing ICP and severity of headache.
 Nausea and vomiting:
 Nausea and vomiting arise from increased intracranial pressure being transmitted to the
area postrema of the medulla.
 In the case of a brain tumour, vomiting can be triggered by abrupt changes in body
position.
 Mass effect:
 A mass effect is the effect of a growing mass that results in secondary pathological
effects by displacing intracranial structures.
 Results in raised ICP, midline shift, herniations, compression of blood vessels,
compression of reticular formation, and in severe cases when brain herniation is
imminent, the presence of Cushing’s triad.
 Cushing’s triad:
 Respiratory depression
 Caused by compression of the respiratory centre in the medulla, which reduces
frequency of breathing and can result in abnormal breathing patterns.
 Hypertension
 Raised ICP reduces cerebral perfusion, resulting in ischaemic hypoxia and
production of H+ ions.
 This decrease in pH triggers central chemoreceptors, which increase sympathetic
stimulation by increasing cardiac output and causing vasoconstriction, raising
blood pressure.
 Bradycardia
 Baroreceptors detect the increase in blood pressure and increase parasympathetic
output to the heart, lowering heart rate in an effort to counteract the hypertension.
 Brain herniations:
 Uncal
 Herniation of the median temporal lobe, especially the uncus, through the
tentorial notch.
 Can compress the oculomotor nerve (CN III), resulting in an ipsilateral dilated
and unresponsive pupil due to a lack of parasympathetic input.
 Can compress the cerebral peduncles, resulting in contralateral hemiplegia due to
interference in the corticospinal tract.
 Can compress the posterior cerebral artery, damaging the primary visual cortex,
resulting in contralateral homonymous hemianopia.
 Can distort the midbrain reticular formation, impacting level of consciousness.
 Central
 Herniation of the diencephalon and brainstem downwards through the tentorium
cerebelli.
 Can cause traction against the abducens nerve (CN VI), resulting in lateral rectus
paralysis.
 Cingulate
 Cingulate gyrus herniates under the falx cerebri into the opposite side of the
cranial cavity.
 Can compress the anterior cerebral artery, causing infarcts that lead to
contralateral weakness and altered sensation in the lower limb.
 Transcalvarial
 Brain squeezes through a fracture or surgical site in the skull.
 Can occur during a craniectomy.
 Upward cerebellar
 Cerebellum herniates upward due to pressure differential if ventricular drainage
is performed, pushing the midbrain downwards through the tentorium cerebelli.
 Downward cerebellar
 Cerebellar tonsils herniate downwards through the foramen magnum, causing
compression of the lower brainstem and cervical spinal cord.
 Pressure causes dysfunction of respiratory and cardiovascular centres.
 Can occur if a lumbar puncture if done and there is no continuous flow between
the brain and spinal cord CSF as a pressure differential is created.
 Clinical Reasoning and Clinical Science:
Headaches:

 Primary headache:
 Makes up 90% of all headaches and not caused by any identifiable disease process or
structural issue.
 Divided into episodic (<15 headaches per month) and chronic daily (>15 headaches per
month).
 Can also be classified on the basis of length (<4 hours or >4 hours).

Type of Headache: Characteristics: Symptoms: Other Information

Migraine  Can have prodromal symptoms 24-48  Photophobia  Can be either
hours before onset (hyperactivity, euphoria,  Phonophobia episodic or chronic
depression, lethargy, craving, yawning etc.)  Nausea  Affects more
 Can have auras 1-2 hours before onset  Vomiting women than men
(focal neurological dysfunction)  Most prevalent in
 Headache phase consists of 4-72 hours of 25-45 age group
moderate to severe unilateral throbbing  Tends to have a
(frontal or diffuse) strong genetic
 Worsened by change in position and component
exercise
Tension  Tight, pressure-like bilateral pain that is  Usually no  Can be either
mild-moderate occurring in a band region associated episodic or chronic
around the head symptoms  Affects more
 Duration is 30 mins – 1 week women than men
Cluster  Excruciating unilateral pain localised to the  Ipsilateral  Affects more men
orbital, supraorbital or temporal regions lacrimation, than women
 Headaches occur in clusters, with each ptosis and
attack lasting 15 mins – 3 hours, and miosis
usually several months separating each  Nasal
cluster of attacks congestion

 Secondary headache:
 Haemorrhage
 A form of space-occupying lesion that may be an epidural haematoma, subdural
haematoma, subarachnoid haemorrhage or intraparenchymal haemorrhage.
 Causes a very abrupt and intense headache due to the sudden raised ICP.
 Very commonly fatal.
 Giant cell arteritis
 Inflammation of cerebral blood vessels, resulting in stenosis, which may cause
headache among other neurological deficits.
 Usually affects the superficial temporal arteries.
 Cerebral venous thrombosis
 Blood clot in dural sinuses, reducing reabsorption of CSF, potentially leading to
infarction and raised ICP.
 Symptoms can match that of a stroke, including limb weakness, altered vision
and changes in mental status.
  Carotid artery dissection
 A tear in the tunica intima, leading to occlusion of the artery that can be
compensated for through anastomotic bilateral circulation.
 May produce thrombo-emboli which cause stroke.
 Hydrocephalus
 There is too much CSF due to obstruction or dysfunction of arachnoid
granulations or choroid plexuses, resulting in raised ICP.
 Intracranial neoplasm
 Brain tumour which can cause headaches through irritation of CNS components,
destruction of brain parenchyma, and raised ICP.
 Encephalitis
 Acute inflammation of the brain due to infection, resulting in fever, headache,
confusion, drowsiness among other focal neurological deficits.
 Meningitis
 Acute inflammation of the meninges due to infection, resulting in fever,
headache, neck stiffness and confusion.
 Red flag features of headaches:
 Onset at an older age with no previous Hx
 New onset in a specific setting such as with cancer or HIV
 New persistent headache
 Focal neurological deficits
 Headache is progressive
 Visual disturbances
 Systemic effects such as fever or weight loss
 Headache with a rash
 Headache with papilloedema, or triggered by coughing/straining
 Very abrupt and intense headache
 Headache with neck stiffness
 Weakness, ataxia or loss of coordination
Pharmacology:
Anticonvulsants:

 Anticonvulsants are drugs that must be taken regularly to prevent further seizures.
 60% of patients can have their seizures controlled with one drug, but some patients need
combinations to maintain adequate control.
 Seizures that respond to different drugs:
 Partial  carbamazepine
 Tonic-Clonic  carbamazepine
 Absence  valproate
 Sodium channel blockers:
 Inhibition of Na+ channel, meaning the neuron is constantly in a refractory period,
preventing repetitive action potentials, stabilising the neuron.
 GABA enhancers:
 Bind to receptors to inhibit uptake or metabolism of GABA, or increase GABA synthesis.
 GABA then hyperpolarises the neuron by opening Cl- channels, causing an influx, which
means it is more difficult for the cell to reach threshold.