Primary brain tumours

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

A primary brain tumour may arise from glial, meningeal, ependymal, neuronal, lymphoid, germ-cell, pituitary-region or nerve-sheath tissue. Symptoms reflect site and rate of growth more than histological label. A slow frontal meningioma may produce subtle apathy for months, whereas a small posterior-fossa mass can obstruct cerebrospinal fluid abruptly. New adult seizure and progressive focal or cognitive change are high-yield presentations.

Emergency CT answers whether there is haemorrhage, hydrocephalus or dangerous shift. MRI with contrast then defines the lesion, non-enhancing infiltration, diffusion, perfusion and surgical relationship to eloquent networks. Imaging patterns guide urgency but overlap: glioblastoma, metastasis, lymphoma, abscess, inflammation and treatment effect can all enhance. When tissue is required, plan resection or stereotactic core through the neuro-oncology MDT and obtain enough material for histology, immunohistochemistry, methylation or sequencing tests that alter classification.

Diffuse gliomas are named by integrated molecular diagnosis. An IDH-mutant tumour with whole-arm 1p/19q codeletion is oligodendroglioma; IDH-mutant non-codeleted disease is astrocytoma. Glioblastoma is usually IDH wild type and biologically aggressive. Molecular diagnosis determines prognosis and the value of radiotherapy and alkylating chemotherapy. Meningioma management is more anatomical: observe selected small asymptomatic lesions, resect growing or symptomatic disease and use radiotherapy for residual, recurrent or higher-grade risk.

Glioblastoma treatment illustrates multimodal care. Maximal safe surgery is followed by external-beam radiotherapy with daily temozolomide and then six or more protocol cycles of adjuvant temozolomide in suitable adults. Frailty, age, MGMT status and patient priorities may favour hypofractionated radiation, temozolomide alone or supportive care. Recurrence is reassessed because pseudoprogression and radionecrosis can mimic growth; repeat surgery, re-irradiation, systemic therapy and trials are selected rather than automatic.

Key points

Primary brain tumours present through seizures, progressive focal deficits, cognitive or personality change, raised intracranial pressure or an incidental imaging finding.
Acute deterioration requires non-contrast CT first because it quickly detects haemorrhage, hydrocephalus, marked mass effect and a lesion needing urgent neurosurgery.
Contrast-enhanced MRI is the preferred definitive imaging test for characterising and mapping a suspected primary brain tumour; include diffusion and other protocol sequences.
A scan cannot reliably define tumour lineage. The diagnostic reference standard for most infiltrative tumours is neurosurgically obtained tissue sufficient for integrated histological and molecular classification.
Maximal safe resection is preferred when feasible because it relieves mass, obtains tissue and improves control, but preservation of language, motor, visual and cognitive function limits extent.
Use neuronavigation, functional MRI, tractography, intraoperative mapping, awake surgery and fluorescence guidance selectively to maximise resection without disabling injury.
Adult diffuse glioma reports must integrate IDH status, 1p/19q codeletion where relevant and other defining molecular features; MGMT promoter methylation predicts temozolomide benefit in glioblastoma.
First-line fit-adult glioblastoma treatment is maximal safe resection or biopsy followed by 60 Gy in 30 fractions with concurrent daily temozolomide, then adjuvant temozolomide.
Give Pneumocystis prophylaxis and monitor blood counts during concurrent temozolomide and radiotherapy according to protocol; lymphopenia may persist.
Dexamethasone treats symptomatic vasogenic oedema, not the tumour. Use the lowest effective dose and taper promptly to reduce infection, hyperglycaemia, myopathy, psychosis and adrenal suppression.
Do not give antiseizure medication routinely to every seizure-naive patient; after a tumour-related seizure, a low-interaction agent such as levetiracetam is commonly first line.
If primary CNS lymphoma is plausible and the patient is neurologically stable, withhold corticosteroid until stereotactic biopsy because lymphoma cells may lyse and yield a non-diagnostic sample.
Meningioma, glioma, ependymal, embryonal, germ-cell, sellar and nerve-sheath tumours follow different surgery, radiotherapy and systemic pathways; the MDT must not treat a radiological label as a final diagnosis.
Early rehabilitation, neuropsychology, seizure and driving advice, endocrine review, work support and palliative care are core brain-tumour treatment rather than optional aftercare.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Predominantly sporadic

Most diffuse gliomas, meningiomas and other adult primary brain tumours arise without a preventable exposure through acquired driver alterations in a susceptible neural or meningeal cell.

Ionising radiation

Previous therapeutic cranial irradiation increases later meningioma, glioma and sarcoma risk after a latency that can extend for decades, unlike ordinary diagnostic imaging exposure.

Inherited tumour syndromes

Neurofibromatosis types 1 and 2, tuberous sclerosis, von Hippel-Lindau, Li-Fraumeni and mismatch-repair syndromes predispose to recognisable tumour combinations and younger presentation.

Immune and viral context

Severe immune compromise increases Epstein–Barr-virus-associated primary CNS lymphoma, while most common gliomas have no proven link to mobile phones, lifestyle or minor head trauma.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Molecular lineage defines diffuse glioma
IDH mutation and 1p/19q codeletion separate oligodendroglioma from astrocytoma, while IDH-wildtype biological features identify aggressive glioblastoma even when morphology appears lower grade.
2
Infiltration limits complete removal
Glioma cells migrate beyond visible enhancement into functioning brain, so maximal safe resection reduces bulk but cannot remove every malignant cell without unacceptable neurological harm.
3
Blood–brain and tumour barriers shape therapy
Variable vascular permeability and efflux limit drug exposure; contrast enhancement marks barrier disruption rather than the complete microscopic tumour boundary.
4
Mass and oedema raise pressure
Tumour, vasogenic oedema, haemorrhage or blocked cerebrospinal-fluid pathways increase intracranial volume, causing headache, vomiting, papilloedema, reduced consciousness and herniation.
5
Location produces networks symptoms
Frontal, temporal, motor, language, visual, brainstem, cerebellar and pituitary-region disease causes different seizure, behavioural, cognitive, focal and endocrine phenotypes independent of tumour grade.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

First adult seizure

A focal aura, impaired awareness, unilateral motor onset or bilateral convulsion can be the first sign of a cortical tumour and needs structural imaging.

Raised intracranial pressure

Progressive headache, morning vomiting, papilloedema, diplopia from sixth-nerve palsy and drowsiness indicate mass, oedema or hydrocephalus.

Focal network dysfunction

Weakness, aphasia, hemianopia, neglect, ataxia or cranial-nerve deficits localise the affected system and inform urgency and operative mapping.

Cognitive or personality change

Executive decline, apathy, disinhibition, memory loss or reduced work performance may precede headache, particularly with frontal or temporal disease.

Impending herniationRed flag

Falling consciousness, anisocoria, extensor response or cardiorespiratory instability requires immediate CT, neurocritical care and neurosurgical decompression assessment.

Sellar or hypothalamic effect

Visual-field loss, ophthalmoplegia, amenorrhoea, galactorrhoea, hypogonadism, diabetes insipidus or cortisol deficiency indicates a different endocrine-neurosurgical pathway.

Red flags requiring action

A first focal or generalised seizure in an adult requires urgent assessment for a structural lesion and appropriate brain imaging.
Progressive morning headache with vomiting, papilloedema, altered behaviour, cognitive decline or focal deficit suggests raised intracranial pressure rather than uncomplicated primary headache.
Rapidly falling consciousness, unequal pupils, extensor posturing or Cushing physiology indicates impending herniation and needs immediate neurosurgical escalation.
A posterior-fossa mass can cause abrupt obstructive hydrocephalus, gait ataxia, cranial-nerve signs and vomiting with limited warning.
New focal weakness, aphasia or visual loss may mimic stroke; acute CT is required, but subacute progression or an infiltrative lesion warrants contrast MRI.
Steroid-responsive enhancement does not prove lymphoma, but unnecessary dexamethasone before biopsy can make primary CNS lymphoma temporarily disappear histologically.
Fever, immune suppression or recent infection with a ring-enhancing lesion raises cerebral abscess or opportunistic infection and requires urgent microbiological and neurosurgical input.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Emergency non-contrast CT brainFirst step
Why
Rapidly detect haemorrhage, hydrocephalus, calcification, major oedema and midline shift in an acutely unwell patient.
Interpretation and limitations
A normal CT does not exclude an infiltrative or posterior-fossa tumour; proceed to MRI when clinical suspicion persists and add contrast only when safe and useful.
02
Preferred contrast MRI brainPreferred
Why
Characterise enhancement, diffusion, infiltration, haemorrhage, perfusion and anatomical relationship for biopsy, resection and radiotherapy planning.
Interpretation and limitations
Image before high-dose steroid when stable, compare T2/FLAIR with enhancement and remember that tumour extends beyond enhancement while inflammation and treatment effect can mimic progression.
03
Reference integrated tissue diagnosis
Why
Obtain morphology and sufficient material for IDH, 1p/19q, ATRX, p53, H3, BRAF and other subtype-defining tests as appropriate.
Interpretation and limitations
Use maximal safe resection when therapeutic or stereotactic core when resection is unsafe; avoid steroid before suspected lymphoma unless deterioration makes treatment unavoidable.
04
Functional and tract mapping
Why
Map motor, language, visual and white-matter pathways when tumour approaches eloquent brain and surgical extent depends on function.
Interpretation and limitations
Functional MRI and tractography support but do not replace direct intraoperative mapping; an awake technique is selected by task, anatomy and patient suitability.
05
Baseline treatment and seizure assessment
Why
Document FBC, renal and liver function, glucose, infection risk, ECG context, neurological baseline and exact seizure semiology before therapy.
Interpretation and limitations
Obtain an EEG for uncertain or ongoing events rather than to exclude a tumour; establish pregnancy, fertility, interacting medicines and corticosteroid complications.
06
Response and recurrence imaging
Why
Distinguish tumour response, pseudoprogression, radionecrosis and true recurrence using serial MRI and selected perfusion, spectroscopy or amino-acid PET.
Interpretation and limitations
Early enhancement after chemoradiation may be treatment related, particularly with MGMT methylation; discuss uncertain change before declaring failure or switching treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Brain metastasis

Multiple grey–white junction lesions and known extracranial cancer favour metastases, but a solitary deposit can mimic glioma and may need tissue before treatment.

Cerebral abscess or infection

Fever, inflammatory markers, immune status, diffusion restriction and infectious source support abscess, yet steroids or antibiotics before aspiration can reduce diagnostic yield.

Demyelination, infarction or haemorrhage

Tumefactive demyelination and subacute vascular lesions can enhance and cause deficits; diffusion, susceptibility, interval evolution and targeted laboratory tests help distinguish them.

Primary CNS lymphoma

Deep periventricular avidly enhancing lesions, diffusion restriction and immune compromise suggest lymphoma, whose biopsy and methotrexate-based treatment differ from glioma.

Non-neoplastic seizure or headache disorder

Primary epilepsy and migraine remain common, but new adult focal seizure, persistent neurological change or raised-pressure features require structural exclusion before attribution.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Acute mass effectStabilise pressure while preserving diagnosisFirst stepA patient has reduced consciousness, progressive deficit, severe vomiting, hydrocephalus or marked imaging mass effect.

1Use ABCDE care, elevate the head, avoid hypoxia and hypotension, treat seizures and obtain urgent CT while contacting neurosurgery and neurocritical care.
2Give dexamethasone for clinically important vasogenic oedema unless stable suspected lymphoma makes diagnostic preservation the higher priority, and treat hydrocephalus with urgent CSF diversion when indicated.
3Proceed to decompression, resection or biopsy according to anatomy and physiology, preserving tissue for integrated pathology before starting tumour-specific therapy.

02New suspected tumourMove from MRI pattern to molecular diagnosisImaging shows a primary brain tumour without immediate herniation.

1Complete contrast MRI, neurological and cognitive baseline, steroid and seizure review and discuss the case in the specialist neuro-oncology MDT.
2Plan maximal safe resection or stereotactic core using functional mapping where required, and route unfixed and fixed material correctly for molecular classification.
3Explain the integrated diagnosis, prognosis and options after postoperative MRI, then build radiotherapy and systemic treatment around age, function, biology and patient priorities.

03New glioblastomaCombine maximal safe surgery with chemoradiationIntegrated pathology confirms glioblastoma in an adult suitable for active multimodal treatment.

1Review postoperative MRI, performance, MGMT status, cognition, steroid need, seizures, fertility and rehabilitation and contour the radiotherapy field with the neuro-oncology team.
2Give 60 Gy in 30 fractions with temozolomide 75 mg/m² daily throughout radiation, blood monitoring and Pneumocystis prophylaxis, adapting for frailty and age.
3After recovery, give adjuvant temozolomide on days 1 to 5 of each 28-day cycle, monitor imaging and toxicity and interpret early enhancement for pseudoprogression before changing course.

04Possible recurrenceConfirm progression before salvageSymptoms or surveillance MRI suggests growth after surgery, radiotherapy or systemic treatment.

1Review steroid dose, seizure control and full serial imaging and use advanced MRI or other imaging when treatment effect remains a realistic explanation.
2Obtain tissue when uncertainty would change management and recheck the molecular diagnosis and acquired targets, balancing operative risk against diagnostic value.
3Select repeat surgery, re-irradiation, systemic treatment, trial or symptom-focused care according to site, interval, biology and functional reserve, with an explicit goal and stopping rule.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides concurrent radiosensitisation and adjuvant alkylating therapy after maximal safe surgery or biopsy in suitable newly diagnosed glioblastoma.

Temozolomide with glioblastoma radiotherapy

Give temozolomide 75 mg/m² orally once daily throughout radiotherapy, including weekends, then commonly 150 mg/m² on days 1 to 5 of cycle 1 and 200 mg/m² on days 1 to 5 every 28 days for later cycles if tolerated.

Check blood counts and liver function, give antiemetic and Pneumocystis prophylaxis during concurrent treatment and monitor lymphopenia, opportunistic infection, thrombocytopenia, hepatic injury, fertility and pregnancy risk.

Rapidly reduces blood–brain-barrier oedema and headache or focal deficits while surgery, radiotherapy or another definitive treatment is organised.

Dexamethasone for tumour oedema

For symptomatic vasogenic oedema use the lowest effective oral or intravenous dose, commonly 4 to 16 mg daily in divided doses according to severity, then taper as neurological pressure improves.

It does not treat glioma; monitor glucose, infection, mood or psychosis, proximal myopathy, gastrointestinal risk, sleep and adrenal suppression and avoid before stable suspected CNS lymphoma biopsy when possible.

Provides a low-interaction first-line antiseizure option after a confirmed brain-tumour-related seizure or perioperative event requiring treatment.

Levetiracetam after tumour-related seizure

Start commonly at 500 mg orally twice daily and titrate to seizure control and renal function, using intravenous equivalent when oral treatment is temporarily impossible.

Do not prescribe routinely to every seizure-naive patient; monitor somnolence, dizziness, irritability, depression and suicidality and provide driving, bathing and adherence advice.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pressure crisis with brain shift

Progressive oedema, hydrocephalus or haemorrhage can abruptly impair consciousness and brainstem function, requiring steroids, CSF diversion or urgent decompression according to cause.

Epilepsy and injury

Cortical irritation causes focal or bilateral tonic–clonic seizures, with risks from status, falls, driving, bathing, medication toxicity and sudden unexpected death.

Persistent neurological disability

Tumour and treatment can impair movement, language, vision, memory, personality, swallowing and continence, altering capacity, work and family roles.

Thrombosis and treatment toxicity

Glioblastoma raises venous-thromboembolism risk, while surgery, radiotherapy, temozolomide and corticosteroids cause infection, cytopenia, endocrine, metabolic, cognitive and wound complications.

Recurrence and malignant evolution

Infiltrating glioma usually recurs near the original field and lower-grade disease can transform, requiring repeat molecular review and changing local or systemic options.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Obtain early postoperative MRI within the local protocol window to document residual enhancing and non-enhancing tumour before surgical change becomes difficult to interpret.
During chemoradiation, review blood counts, liver function, nausea, infection, lymphopenia, skin, fatigue, cognition, neurological deficit, seizures and corticosteroid requirement.
At every visit reconcile dexamethasone dose and taper; screen glucose, sleep, mood, muscle weakness, infection and adrenal-risk education rather than letting steroid continue indefinitely.
Use serial MRI at tumour-specific intervals and compare the full sequence and clinical trajectory, applying response criteria and considering pseudoprogression or radionecrosis.
Track seizure frequency, adverse effects, rescue plan and driving restrictions and involve epilepsy services for refractory, uncertain or interaction-heavy events.
Assess cognition, communication, swallowing, mobility, visual field, endocrine function, capacity, work and caregiver burden with timely rehabilitation and neuropsychology.
Introduce advance-care and preferred-place discussions according to prognosis and readiness while continuing active treatment and rapidly controlling headache, nausea, seizures and distress.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Enhancement is barrier failure

It is not a precise tumour edge: infiltrating glioma extends into non-enhancing brain and treatment injury can also enhance strongly.

Function defines maximal resection

Removing more tissue helps only while language, movement, vision, cognition and independence remain acceptably protected through mapping and patient choice.

Steroids can erase lymphoma

Dexamethasone causes rapid lymphoid apoptosis, so a stable patient with possible CNS lymphoma should reach biopsy before exposure whenever safe.

MGMT is predictive, not a verdict

Promoter methylation increases expected temozolomide benefit, particularly in older patients, but treatment decisions still include performance and individual goals.

Early progression may be false progression

Inflammation and blood–brain-barrier change after chemoradiation can mimic tumour growth, requiring serial and advanced interpretation before abandoning effective therapy.

Driving advice is treatment

A brain tumour or seizure can legally restrict driving; explicit regulator notification and safety counselling prevents harm beyond the clinic.

11Common pitfallsFrequent interpretation and management errors.

01
Treating new adult seizure as idiopathic without brain imaging.
02
Using a normal non-contrast CT to exclude an infiltrative or posterior-fossa tumour.
03
Naming glioblastoma, lymphoma or metastasis from MRI alone when tissue is safely obtainable.
04
Giving dexamethasone before biopsy in a stable patient with suspected primary CNS lymphoma.
05
Continuing high-dose steroid after oedema improves without a written taper.
06
Using prophylactic antiseizure medicine indefinitely in every seizure-naive patient.
07
Reporting diffuse glioma without integrated molecular classification.
08
Pursuing radiological extent at the cost of disabling eloquent-brain injury.
09
Calling early post-radiation enhancement recurrence without considering pseudoprogression.
10
Focusing on survival while omitting cognition, capacity, driving, rehabilitation and caregiver support.