Brain Tumours

• Primary brain tumours are rare: ~6 per 100,000 per year ^[2].
• Brain tumours account for 1–2% of all malignancies but 13% of all malignancy-related deaths — disproportionately lethal because of the critical, unforgiving location ^[3].
• Secondary (metastatic) tumours are far more common than primary tumours: secondary tumours are approximately 6–10× more common than primary ones ^[3]. Metastatic disease complicates ~25% of extracranial malignancies, and incidence is rising as systemic anticancer therapy improves patient lifespan (the brain becomes a "sanctuary site" behind the blood–brain barrier) ^[1][2].
• Pituitary adenomas account for 6–18% of all brain tumours and are found in 12–22% at autopsy ^[4][5].

Tumour locations and types depend on age ^[3]:

• Meningiomas: Female > Male (~2:1), due to progesterone/oestrogen receptor expression on tumour cells.
• Glioblastoma (GBM): Male > Female (~1.6:1).
• Medulloblastoma: Male > Female in children.

The brain is enclosed in the rigid skull (Monro-Kellie doctrine: total intracranial volume of brain + CSF + blood is fixed). Any added mass must displace one of these components or intracranial pressure (ICP) rises.

Supratentorial compartment (above tentorium cerebelli):

• Cerebral hemispheres (frontal, parietal, temporal, occipital lobes)
• Basal ganglia, thalamus
• Lateral and 3rd ventricles
• Sellar/parasellar region (pituitary, optic chiasm, cavernous sinus)

Infratentorial compartment / Posterior fossa (below tentorium cerebelli):

• Cerebellum
• Brainstem (midbrain, pons, medulla)
• 4th ventricle
• Cerebellopontine angle (CPA)

Pathology: Secondary tumours are 6–10× more common than primary tumours ^[3].

Commonest intracranial tumour in adults ^[2]. Key points:

Route of spread: Haematogenous or direct invasion — NOT lymphatic, because the brain does not have conventional lymphatic drainage ^[2].

Sites of metastasis: ~80% cerebral hemisphere, ~15% cerebellum, ~5% brainstem ^[2]. The commonest location is the watershed area between major arterial supplies and the grey-white junction — because blood vessel diameter decreases at this point, acting as a "trap" for tumour cell clumps ^[2].

• Nasopharyngeal carcinoma (NPC): endemic in Hong Kong, can invade the skull base directly (through foramen lacerum) and cause cranial nerve palsies. While not a "brain tumour" per se, NPC with intracranial extension is a common differential in the Hong Kong context ^[8].
• Lung cancer: the leading cause of brain metastases in Hong Kong due to high incidence of both smoking-related and EGFR-mutant lung cancers.
• Hepatocellular carcinoma (HCC): while the most common primary cancer in Hong Kong, brain metastases from HCC are relatively uncommon but do occur ^[9].
• Primary CNS lymphoma: increasingly recognised, especially with immunosuppressed patients (post-transplant, HIV). EBV-driven.

Brain tumours produce symptoms through several distinct pathophysiological mechanisms. Understanding these is essential because different mechanisms respond to different treatments.

High-grade diseases tend to present with subacute onset of signs and symptoms of raised ICP ^[2].

The Monro-Kellie doctrine states that the cranial vault is a fixed-volume container. ICP rises when the total volume of brain + CSF + blood exceeds the compensatory capacity of the system.

Mechanisms of raised ICP in brain tumours ^[3]:

Low-grade diseases tend to present with slowly progressive focal neurological symptoms ^[2].

Focal deficits arise from ^[1][2]:

• Neuronal destruction — direct tumour infiltration kills neurons (irreversible)
• Pressure effect — compression displaces but does not yet kill neurons (partially reversible with surgery)
• Oedema — vasogenic oedema compresses surrounding tissue (reversible with steroids — this is why dexamethasone can dramatically improve neurological deficits in brain tumours) ^[1]
• Loss of neuronal function — disconnection syndromes (white matter tract disruption)

The focal deficit is location-specific, which enables clinical localisation of the lesion ^[1]. If clinical deficits do not correlate with neuroimaging, consider the possibility of other concomitant pathologies ^[2].

Epilepsy affects 50–80% of primary tumours and 10–20% of secondary tumours ^[2].

Why are brain tumours epileptogenic?

• Peri-tumoural cortex is irritated by oedema, ischaemia, neurotransmitter imbalances (excess glutamate released by glioma cells), altered local ion concentrations, and blood products (from micro-haemorrhages).
• The irritated cortex fires abnormally → seizure.

Key points about tumour-related epilepsy ^[2]:

• Site: always supratentorial — infratentorial (cerebellar) cortex is inhibitory in nature and does not generate seizures.
• Types: typically repetitive and stereotyped in a given patient — focal seizures (simple or complex) ± secondary generalisation.
• Low-grade gliomas (especially oligodendrogliomas and WHO grade II astrocytomas) have the highest seizure rates because they infiltrate cortex without destroying it, creating a large area of peri-tumoural irritation.

When ICP rises asymmetrically, brain tissue shifts from high-pressure to low-pressure compartments ^[1]:

• Hypersecretion: Functioning pituitary adenomas autonomously secrete hormones (prolactin, GH, ACTH, TSH) ^[4][5].
• Hyposecretion: Non-functioning adenomas or craniopharyngiomas compress normal pituitary tissue and/or the pituitary stalk, causing hypopituitarism. The classical order of hormone loss reflects differential sensitivity: GH → FSH/LH → ACTH → TSH ^[4][5]. (GH-producing cells are the most abundant and peripherally located, hence most vulnerable to compression.)
• Stalk effect: Compression of the pituitary stalk interrupts dopamine delivery from the hypothalamus → loss of tonic inhibition of prolactin secretion → mild hyperprolactinaemia (typically < 100 ng/mL, unlike true prolactinomas where prolactin is usually > 200 ng/mL).

The current WHO classification (5th edition, 2021) integrates both histological features and molecular markers — a paradigm shift from the purely morphological classifications used previously. Key grading parameters include:

• Mitotic activity
• Invasiveness (infiltration into surrounding brain)
• Microvascular proliferation
• Necrosis (especially pseudopalisading necrosis in GBM)

WHO Grading: Grades I–IV (applicable to gliomas):

Distinguishing "benign" vs "malignant" (metastasises outside CNS) is less important for brain tumours ^[3]. Instead, classification by the following three parameters is more clinically useful:

1. Histological features: mitosis, invasiveness, vascular proliferation, necrosis ^[3]
2. Anatomical location: risk of fatal or severe neurological consequences ^[3]
3. Possibility of surgical removal: risk of recurrence ^[3]

As discussed above under Aetiology, this is the most important imaging distinction:

• Intra-axial: Gliomas, metastases, primary CNS lymphoma
• Extra-axial: Meningiomas, schwannomas, pituitary adenomas, craniopharyngiomas

Brain tumours present through three cardinal mechanisms ^[1][2]:

1. Raised ICP — subacute onset headache, vomiting, papilloedema (high-grade tumours)
2. Focal neurological deficits — slowly progressive, location-specific (low-grade tumours)
3. Epilepsy — supratentorial tumours, especially low-grade gliomas

Additionally: 4. Hormonal dysfunction — pituitary adenomas, craniopharyngiomas 5. Incidental finding — increasingly common with widespread CT/MRI use 6. Pituitary apoplexy — neurosurgical emergency

Pituitary tumours may present as incidental findings on:

• Skull X-ray: double-flooring of sella turcica (due to asymmetrical enlargement of the pituitary fossa)
• CT/MRI brain performed for other reasons (e.g., head injury, headache work-up)

CN VI palsy is a famous "false localising sign" of raised ICP — it does not localise the tumour itself. CN VI has the longest intracranial course and is stretched over the clivus/petrous ridge when ICP rises diffusely. Therefore, a posterior fossa tumour can cause bilateral CN VI palsies even though the tumour is nowhere near CN VI.

Other causes of CN VI palsy that may overlap with brain tumour presentations ^[11]:

• Pontine lesion (infarction, demyelination, tumour)
• Microvascular disease (most common overall cause in adults with vascular risk factors)
• Petrous bone pathology (petrositis — Gradenigo syndrome)
• Cavernous sinus pathology (infection, ICA aneurysm, CST)
• Orbital pathology (tumours, cellulitis)

In Hong Kong, NPC (nasopharyngeal carcinoma) with skull base invasion is an important cause of CN VI palsy in young patients ^[11]. Always consider this in the local context.

Slowly growing tumours (especially frontal meningiomas, low-grade gliomas) can present insidiously with personality change, cognitive decline, and apathy — mimicking neurodegenerative dementia (especially frontotemporal dementia). Conversely, FTD can be mistaken for a tumour. Neuroimaging is essential to distinguish these.

The clinical presentation raises suspicion. The three cardinal presentations from the previous section are:

• Raised ICP: Subacute progressive headache (worse in morning), vomiting, papilloedema
• Focal neurological deficit: Progressive, location-specific
• Seizures: New-onset in an adult, especially focal with secondary generalisation

Red flags that should trigger urgent neuroimaging:

• New-onset seizure in an adult
• Progressive focal neurological deficit
• Headache with features of raised ICP (morning headache, vomiting, papilloedema)
• Personality/cognitive change with no other explanation
• Known cancer patient with new neurological symptoms

CT brain ± contrast is often the first-line imaging in the acute or emergency setting ^{[2][5][7][13][14]}:

Why CT first?

• Widely available, fast (seconds), no sedation needed
• Detects acute blood (hyperdense), calcification, mass effect, hydrocephalus
• Adequate to detect large lesions and guide emergency management (e.g., herniation requiring urgent intervention)

What to look for on CT ^[5][13]:

Functional imaging is used for pre-operative planning ^[2]:

The definitive diagnosis of a brain tumour requires tissue — obtained by either surgical resection or stereotactic biopsy ^[1][2].

Principles of brain tumour surgery ^[1]:

• Obtain histological diagnosis
• Maximal safe removal
• Preserve life
• Preserve function
• "Resection margin" is difficult in neurosurgery

Surgical approaches ^[2]:

• Craniotomy: Flap of bone cut and reflected — for resection of accessible tumours
• Burr hole: Often for stereotactic biopsy
• Craniectomy: Burr hole + removal of surrounding bone — for decompression
• Transsphenoidal (transnasal or sublabial): For pituitary tumours ^[2]
• Transoral: For anterior foramen magnum/upper cervical lesions

Stereotactic biopsy ^[2]:

• Usually for non-resectable tumours (e.g., pontine gliomas) or lymphoma (which is not treated by surgery — biopsy only) ^[1][2]
• Uses frameless stereotaxy or frame-based systems with image guidance to precisely target lesion

Tissue is processed for ^[2]:

1. Histopathology: H&E staining → assess mitosis, necrosis, microvascular proliferation, cellular atypia
2. Immunohistochemistry: GFAP (astrocytic marker), synaptophysin (neuronal), EMA (meningioma), Ki-67 (proliferation index), CD20 (B-cell lymphoma)
3. Molecular pathology (essential in WHO CNS5, 2021):
   • IDH1/2 mutation status (most important prognostic marker in diffuse gliomas)
   • 1p/19q co-deletion (defines oligodendroglioma)
   • MGMT promoter methylation (predicts temozolomide response in GBM)
   • H3K27M mutation (defines diffuse midline glioma)
   • ATRX loss (associated with IDH-mutant astrocytoma)
   • BRAF V600E (seen in pleomorphic xanthoastrocytoma, some paediatric gliomas — actionable target)
   • TERT promoter mutation (associated with GBM)

A systemic malignancy screen should be performed if the clinical or radiological picture suggests metastatic disease ^[2]:

Steroids (e.g., dexamethasone) ^[1][2]:

Mechanism: Dexamethasone reduces vasogenic oedema by restoring blood–brain barrier (BBB) integrity. It decreases capillary permeability and reduces VEGF expression by tumour cells. The result is a rapid decrease in peri-tumoural oedema → reduction in mass effect → improvement in neurological symptoms, sometimes dramatically within hours.

Why dexamethasone specifically? Dexamethasone is preferred over other corticosteroids because:

• It has minimal mineralocorticoid activity (does not cause salt/water retention → less cerebral oedema exacerbation)
• Long half-life (~36 hours) → convenient dosing
• High glucocorticoid potency

Dosing ^[2]:

• PO (or IV if severe) dexamethasone 10 mg loading then 4 mg Q4h or 8 mg BD

Indications ^[1]:

• ↓ Cerebral oedema and relieve symptoms
• Peri-operative use (to reduce surgical swelling)
• Palliation (in inoperable tumours)
• Raised ICP due to CNS infections and brain tumours ^[15]

Contraindications/Cautions ^[1][2]:

• Exclude infection first — steroids will immunosuppress and worsen CNS infections (e.g., abscess, TB) ^[1]
• C/I: suspected CNS lymphoma → steroid causes acute lysis of lymphocytes → ↓ diagnostic yield on biopsy (the "ghost tumour" phenomenon) ^[2]
• Avoid in cerebral infarction or haemorrhage — steroids worsen outcomes in stroke ^[15]

Side effects ^[1][2]:

• DM (diabetes mellitus) — glucocorticoid-induced hyperglycaemia
• Immunosuppression — increased infection risk
• Peptic ulcer — need PPI prophylaxis
• Proximal myopathy (chronic use), osteoporosis, Cushingoid features, psychosis

Anticonvulsants (e.g., phenytoin, levetiracetam) ^[1][2]:

Mechanism: Brain tumours cause seizures via peri-tumoural cortical irritation (glutamate excitotoxicity, ionic imbalances, oedema). Anticonvulsants stabilise neuronal membranes or modulate neurotransmitter activity.

Levetiracetam (Keppra) is the most commonly used in the brain tumour setting ^[2]:

• Favourable drug interaction profile (does not induce hepatic CYP450 enzymes, unlike phenytoin or carbamazepine — important because chemotherapy agents like temozolomide are hepatically metabolised)
• Fewer side effects than older agents
• No need for therapeutic drug monitoring

Indications ^[1][2]:

• Prophylaxis or treatment (if patient has already had a seizure)
• Not for infratentorial lesions ^[1] — because the cerebellar cortex is inhibitory and does not generate seizures ^[2]
• Usually not for primary prophylaxis in patients who have never had a seizure ^[2] — evidence does not support routine prophylactic AEDs in brain tumour patients without prior seizures (AAN guidelines)

Exceptions where primary prophylaxis may be considered:

• Peri-operative period (perioperative seizure prophylaxis for supratentorial craniotomy — typically for 7 days post-op)
• Melanoma brain metastases (higher seizure risk)

Tranexamic acid — perioperatively to reduce bleeding ^[1].

Tranexamic acid (from Latin trans = across + amine + acid) is an antifibrinolytic — it inhibits plasminogen activation, preventing the breakdown of fibrin clots. Used during craniotomy to reduce intraoperative blood loss.

For acute raised ICP due to brain tumour with mass effect ^[15]:

Principles of brain tumour surgery ^[1]:

• Obtain histological diagnosis
• Maximal safe removal — remove as much tumour as possible without causing new neurological deficits
• Preserve life
• Preserve function
• "Resection margin" is difficult in neurosurgery — unlike extracranial surgery, you cannot take wide margins around brain tumours because surrounding tissue is functional ^[1]

Key surgical decisions ^[1]:

• Whether/When to resect?
• How to resect?
• How much to resect?

Spectrum of surgical intervention by tumour type ^[1]:

Modern neurosurgery employs several adjunctive technologies to maximise safe resection:

Rehabilitation is a critical component of post-operative care ^[2]:

• Physiotherapy, occupational therapy, speech therapy, clinical psychology

Radiosurgery for brain metastasis ^[1]:

• Size limit ~2.5–3 cm but can treat multiple lesions ^[1]
• Radiation necrosis can occur as a complication ^[1]
• Now more preferred over WBRT as adjuvant RT after surgery ^[2]
• Alternative to surgery if small/inoperable, or for small oligometastases ( < 3 cm) ^[2]

Treatment for malignant glioma (WHO III or IV) ^[1]:

• Maximal safe surgical removal where feasible
• Chemoirradiation with temozolomide (TMZ)
  • Standard therapy
  • TMZ is an alkylating agent — it adds alkyl groups to DNA bases (particularly O6-guanine), causing DNA mismatch → triggers apoptosis in tumour cells
  • Concomitant TMZ + ERT, then adjuvant TMZ ^[1] — this is the Stupp protocol (TMZ given daily during 6 weeks of RT, then 6 cycles of adjuvant TMZ, 5 days per 28-day cycle) ^[2]
• Anti-angiogenesis agents — e.g., bevacizumab ^[1] — a monoclonal antibody against VEGF (vascular endothelial growth factor). By blocking VEGF, it reduces tumour angiogenesis and vasogenic oedema. Used as second-line therapy or at recurrence.
• Tumour Treating Fields (TTF) ^[1] — a novel modality using alternating electric fields delivered via adhesive transducer arrays on the shaved scalp. The electric fields disrupt mitotic spindle formation in dividing tumour cells, selectively inhibiting rapidly dividing cells. Approved as adjuvant treatment alongside TMZ.

MGMT promoter methylation — a critical molecular biomarker:

• MGMT (O6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that removes alkyl groups from O6-guanine — directly reversing the damage caused by TMZ.
• If the MGMT promoter is methylated (silenced), the tumour cannot repair TMZ-induced DNA damage → better response to TMZ and improved survival.
• If MGMT is unmethylated → the tumour repairs TMZ damage efficiently → poorer response.

Primary CNS lymphoma is treated with high-dose methotrexate (HD-MTX)-based chemotherapy (typically ≥ 3.5 g/m²) ± whole brain RT:

• Methotrexate at standard doses does not cross the BBB — high doses are required to achieve therapeutic CNS concentrations.
• RT alone leads to high relapse rates and neurocognitive toxicity — combination chemo-RT improves outcomes.
• In elderly patients, HD-MTX alone (without RT) may be preferred to avoid RT-induced cognitive decline.

Target therapy and immunotherapy are increasingly used in brain tumours ^[1]:

Pituitary apoplexy — acute visual loss, hormonal crisis, SAH ^[1]:

Management ^[2]:

• Steroid cover — hydrocortisone 100 mg IV stat then 50 mg Q8h (adrenal crisis is the immediate life-threat)
• Urgent surgical decompression (transsphenoidal) if:
  • Signs of raised ICP
  • Change in conscious state
  • Evidence of compression on neighbouring structures (progressive visual loss, CN III palsy)
• If haemodynamically stable with mild symptoms → conservative management with close monitoring may be acceptable

• External ventricular drain (EVD): Catheter placed into lateral ventricle → drains CSF externally → immediate ICP reduction ^[15]
• CSF shunting (VP shunt): Long-term solution for chronic hydrocephalus ^[2]
• Endoscopic third ventriculostomy (ETV): Puncture floor of 3rd ventricle → bypasses obstruction → particularly useful for obstructive hydrocephalus from pineal region or posterior fossa tumours ^[2]

• ABC assessment and stabilisation
• Dexamethasone IV + mannitol/hypertonic saline
• Emergency craniotomy/craniectomy for decompression
• EVD if hydrocephalus contributing

This is the most feared complication of brain tumours and the most common cause of death.

Brain herniation due to tumour ^[1] — when a growing tumour creates an asymmetric pressure gradient, brain tissue shifts from a high-pressure compartment to a low-pressure one through rigid anatomical openings:

Why is tonsillar herniation immediately lethal? The medulla contains the cardiovascular and respiratory centres. Compression or ischaemia of the medulla knocks out these vital centres, leading to apnoea and cardiac arrest within minutes.

Tumours in certain locations physically block CSF flow:

• Posterior fossa tumours (medulloblastoma, ependymoma, cerebellar astrocytoma) → block the 4th ventricle or cerebral aqueduct
• Pineal region tumours → compress the cerebral aqueduct → hydrocephalus with raised ICP ^[2]
• Colloid cyst of the 3rd ventricle → intermittent ball-valve obstruction of the foramen of Monro → sudden hydrocephalus → can cause sudden death
• Large suprasellar tumours (craniopharyngioma, pituitary macroadenoma) → may compress the 3rd ventricle from below

Communicating hydrocephalus can also occur from leptomeningeal carcinomatosis — tumour cells coating the meninges impair CSF absorption at the arachnoid granulations ^[3].

Seizures affect 50–80% of primary tumours and 10–20% of secondary tumours ^[2]. Seizures can occur as a presenting feature but also as a complication during the disease course:

• Status epilepticus — prolonged or recurrent seizure activity without recovery of consciousness between episodes. This is a medical emergency because sustained seizure activity causes excitotoxic neuronal death, hyperthermia, rhabdomyolysis, metabolic acidosis, and can be fatal.
• Post-ictal Todd's paralysis — transient focal weakness following a seizure that can be confused with tumour progression or stroke ^[3].
• Seizures are usually associated with slow-growing tumours that involve cortex (e.g., meningioma, low-grade glioma) ^[3] — because these tumours create a large penumbra of irritated but functioning cortex.

Tumour haemorrhage ^[1]:

Some brain tumours are prone to spontaneous haemorrhage, presenting acutely mimicking a stroke:

• Bleeding glioblastoma mimicking haemorrhagic stroke ^[1] — GBM has abnormal, fragile neovasculature (formed in response to VEGF) that is prone to rupture. The resulting intracerebral haemorrhage can be the first presentation of the tumour.
• Other tumours prone to haemorrhage: metastatic melanoma (characteristically haemorrhagic), choriocarcinoma, renal cell carcinoma metastases, oligodendroglioma (cortical location + fine branching capillary network).
• Pituitary apoplexy — acute haemorrhagic infarction ± SAH ^[1] — discussed below.

Pituitary apoplexy — an emergency!! ^[1][2]

Acute haemorrhagic infarction ± SAH ^[1]:

• Typically occurs in a pre-existing pituitary adenoma (often undiagnosed)
• Pathophysiology: The adenoma outgrows its blood supply → infarction → haemorrhagic transformation → sudden expansion of the sella contents

Clinical features ^[1][2]:

• Headache — excruciating, sudden onset (stretching of diaphragma sellae + meningeal irritation if SAH)
• Visual loss — acute compression of optic chiasm and/or optic nerves
• Diplopia — CN III palsy (lateral extension into cavernous sinus)
• Acute cortisol insufficiency requiring replacement ^[1] — this is the immediate threat to life. The haemorrhagic infarction destroys corticotroph cells → acute hypocortisolism → adrenal crisis (hypotension, shock, death if untreated)
• Coma — if severe

Critical management point ^[1]:

• Give cortisol before T4 — if you replace thyroid hormone before cortisol in a patient with pan-hypopituitarism, the increased metabolic rate from T4 accelerates cortisol catabolism → precipitates life-threatening adrenal crisis. Always replace cortisol first.
• Which can predispose to DI — once cortisol is replaced, previously masked diabetes insipidus may become apparent (cortisol is needed for free water excretion; without it, water retention masks DI) ^[1]

• Papilloedema from chronically raised ICP → if untreated, chronic papilloedema can cause permanent optic nerve damage ^[17]. The mechanism: sustained raised ICP → transmitted along optic nerve sheath → "tourniquet effect" on optic nerve axons → progressive axonal damage → optic atrophy → irreversible visual loss.
• Bitemporal hemianopia from chiasmal compression (pituitary adenoma, craniopharyngioma) — if not addressed, leads to progressive visual field loss and eventually blindness.

Tumours in the sellar/suprasellar region can cause:

• Hypopituitarism — classically GH → FSH/LH → ACTH → TSH (order of loss) ^[4][5] — the most vulnerable cells are compressed first as the tumour expands
• Cranial diabetes insipidus — stalk compression or hypothalamic infiltration → loss of ADH → polyuria, polydipsia. Classic association: craniopharyngioma, germinoma ^[5]
• Hypothalamic damage — from craniopharyngioma: hyperphagia, obesity, loss of thirst sensation, disturbance of temperature regulation ^[5]

Brain tumour patients (especially those with high-grade gliomas) have a markedly elevated risk of VTE:

• Deep vein thrombosis (DVT) and pulmonary embolism (PE)
• Mechanisms: (1) Tumour cells release tissue factor and other procoagulants → hypercoagulable state; (2) Immobility (from neurological deficits or post-operative bed rest); (3) Surgery and dexamethasone further increase VTE risk; (4) Brain tumours can directly cause DIC (release of procoagulant factors) ^[18]
• GBM patients have one of the highest VTE rates of any cancer — up to 20–30% over the disease course
• Management: Mechanical prophylaxis (TED stockings, intermittent pneumatic compression) for all; pharmacological prophylaxis (LMWH) post-operatively once haemostasis is secure

Certain tumours have a propensity to seed through the CSF pathways — "drop metastases":

• Medulloblastoma — the classic example; craniospinal irradiation is given to address this risk
• Ependymoma — can seed along ventricular system
• Pineoblastoma and intracranial germ cell tumours
• Leptomeningeal carcinomatosis — from brain metastases (especially breast, lung, melanoma) or primary CNS tumours spreading along the meninges → communicating hydrocephalus, multiple cranial nerve palsies, radiculopathies

• Extradural spinal metastases from primary brain tumours are rare (brain tumours rarely metastasise outside the CNS), but spinal cord compression from haematogenous metastases of the same primary cancer (e.g., lung CA) is very common ^[2].
• Sphincter dysfunction is a point of no return ^[19] — once established, neurological recovery after decompression is poor. This underscores the need for urgent investigation and treatment.

Post-operative complications of craniotomy for brain tumour ^[2]:

Rehabilitation is a critical part of post-operative care ^[2]:

• Physiotherapy, occupational therapy, speech therapy, clinical psychology

Complications of transsphenoidal surgery ^[1][2]:

This is essential knowledge as highlighted in the lecture slides ^[1]:

Complications of cranial irradiation ^[2]:

Radiation necrosis deserves special emphasis ^[1][2]:

• Radiation necrosis can occur after radiosurgery for brain metastases ^[1]
• It is the most diagnostically challenging chronic complication because it mimics tumour recurrence on imaging
• Distinguishing features on MRI: high oedema-to-enhancement volume ratio (more oedema than expected for the amount of enhancement), lack of clearly defined T2W lesion, improvement over time without treatment
• Advanced imaging: MR perfusion (low rCBV in necrosis vs high in tumour), MR spectroscopy (high lipid/lactate without elevated choline in necrosis), FDG-PET (hypometabolic in necrosis)

When VP shunts or EVDs are placed for tumour-related hydrocephalus:

The last point — tumour seeding via VP shunt — is a unique and devastating complication. Tumour cells (especially from medulloblastoma, ependymoma, or germ cell tumours) can travel through the shunt catheter and seed the peritoneal cavity, creating extracranial metastases. This is one of the rare circumstances where brain tumours spread outside the CNS.

Both can complicate brain tumours, brain surgery, and SAH (from pituitary apoplexy):

CSWS is an important differential diagnosis of SIADH ^[18]:

• Both can follow head pathologies (cerebral surgery, head injury, SAH, cerebral tumour)
• CSWS results in renal Na loss → hypovolaemic hyponatraemia vs SIADH results in renal water retention → euvolaemic hyponatraemia (different treatment!) ^[18]

Brain tumours are a recognised cause of DIC ^[18] — tumour cells (especially GBM and other high-grade gliomas) release tissue factor and other procoagulant substances, activating the coagulation cascade systemically. This can present as:

• Bleeding tendency (consumption of clotting factors and platelets)
• Microangiopathic haemolytic anaemia (MAHA)
• Multi-organ dysfunction

Patients with brain tumours often have significant neurological deficits and reduced mobility:

• DVT and PE (as discussed above)
• Aspiration pneumonia — from dysphagia (bulbar palsy from brainstem tumours, reduced consciousness)
• Pressure sores — from immobility
• Urinary tract infections — from catheterisation or neurogenic bladder
• Contractures — from prolonged immobility + spasticity