How should I evaluate a patient with new progressive neurological symptoms (persistent headache, seizures, focal weakness, visual or speech changes, cognitive decline, or unexplained nausea/vomiting) for a possible brain tumour?

Evaluation of Suspected Brain Tumour

Obtain an urgent contrast-enhanced MRI brain (≥1.5-T field strength) with pre- and post-contrast T1-weighted, T2-weighted/FLAIR, and diffusion-weighted imaging sequences as the gold standard for detecting brain tumours in any patient presenting with progressive neurological symptoms. 1

Initial Clinical Assessment

Key Historical Features to Elicit

• Headache characteristics: Morning headaches that worsen with Valsalva maneuver, improve with upright posture throughout the day, and may awaken the patient from sleep suggest raised intracranial pressure 1, 2
• Symptom timeline: Brain metastases typically develop over weeks, whereas primary brain tumours (glioblastomas) progress over weeks to months 1, 2
• Cancer history: Active or prior malignancy—particularly lung cancer (especially non-squamous), melanoma (stage IV), HER2-positive or triple-negative breast cancer—substantially increases pre-test probability for brain metastases 1, 2
• Seizure characteristics: New-onset seizures occur in 20-50% of brain tumour patients and are more common with cortical involvement or tumour hemorrhage 1, 3

Neurological Examination Priorities

Perform a detailed, standardized neurological examination documenting:

• Focal deficits: Hemiparesis, hemisensory loss, visual field defects, or aphasia indicate specific anatomical localization 1
• Cranial nerve examination: Multiple cranial neuropathies suggest leptomeningeal involvement rather than parenchymal mass 1
• Cognitive assessment: Personality changes, memory impairment, or confusion may reflect frontal lobe involvement or diffuse cerebral edema 1, 2
• Gait and coordination: Ataxia or gait disturbance may indicate cerebellar or posterior fossa lesions 1
• Papilledema: Fundoscopic examination is essential to detect elevated intracranial pressure 1

The European Association of Neuro-Oncology recommends using standardized assessment forms (e.g., NANO criteria for brain tumours or LANO criteria for leptomeningeal disease) at diagnosis and follow-up 1

Neuroimaging Protocol

Primary Imaging Study

MRI brain with and without gadolinium contrast (minimum 1.5-T, preferably 3.0-T field strength) is mandatory and must include: 1, 2, 4

• Pre- and post-contrast T1-weighted sequences (including 3D volumetric acquisition)
• T2-weighted and/or T2-FLAIR sequences
• Diffusion-weighted imaging (DWI)
• Post-gadolinium 3D FLAIR sequences for leptomeningeal assessment

Key diagnostic MRI features of brain metastases include: 1

• Solid or ring enhancement at grey-white matter junction
• Perifocal vasogenic edema
• Predilection for vascular border zones
• Multiple lesions (>50% of cases)

Key diagnostic MRI features of glioblastoma include: 2, 5

• Irregular ring enhancement with central necrosis
• Infiltrative margins
• Vascular proliferation
• Typically solitary lesion

When to Add Advanced Imaging

• Magnetic resonance spectroscopy (MRS) and perfusion imaging: Consider when distinguishing metastases from other pathologies (abscess, demyelination, primary tumour) is uncertain 1, 2
• Complete spine MRI with gadolinium: Obtain if clinical examination reveals multifocal deficits, radicular symptoms, or cranial nerve palsies suggesting leptomeningeal spread 1, 2
• MR venography: Add if empty sella or other signs of elevated intracranial pressure without mass lesion are present 6

Role of CT Imaging

Non-contrast CT head is appropriate only when: 1

• MRI is contraindicated or unavailable
• Acute hemorrhage or hydrocephalus requires immediate assessment
• Patient is too unstable for MRI

CT has critical limitations: it misses small metastases, has poor sensitivity for posterior fossa lesions (as low as 10% for brainstem infarcts), and provides inadequate soft tissue characterization 1, 4

Risk Stratification for Screening

High-Risk Patients Warranting Screening MRI Even Without Symptoms

Screen at cancer diagnosis in: 1

• Non-squamous non-small cell lung cancer (except stage I)
• Stage IV melanoma
• Metastatic HER2-positive breast cancer
• Metastatic triple-negative breast cancer

This approach detects asymptomatic brain metastases in approximately 75% of cerebral hemisphere locations, 21% cerebellar, and 3% brainstem 1

Differential Diagnosis Considerations

When Biopsy is Essential

Tissue diagnosis should be obtained when: 1

• Imaging findings are atypical or non-diagnostic
• No known primary malignancy exists
• Single lesion in patient without cancer history
• Lesion characteristics suggest infection, demyelination, or other non-neoplastic process

The European Association of Neuro-Oncology emphasizes that no combination of imaging features distinguishes brain metastases from other pathologies with absolute certainty 1

Red Flags for Alternative Diagnoses

• Leptomeningeal metastasis: Multifocal cranial neuropathies, radicular pain, cauda equina syndrome, and sulcal/ependymal enhancement on MRI 1, 2
• Primary CNS lymphoma: Periventricular location, homogeneous enhancement, restricted diffusion, and immunocompromised state 2, 4
• Abscess: Restricted diffusion of cystic content, smooth thin rim enhancement, and systemic infection signs 1

Ancillary Studies

CSF Analysis Indications

Perform lumbar puncture with CSF cytology when: 1, 2

• MRI shows leptomeningeal enhancement
• Multiple cranial neuropathies or radicular symptoms are present
• Imaging is equivocal but clinical suspicion for leptomeningeal disease is high

Process fresh CSF samples within 30 minutes and request immunocytochemical staining for tumour-specific markers 2

Systemic Staging

In patients with confirmed brain metastases but no known primary: 2

• Chest CT to evaluate for lung primary
• PET-CT for systemic staging
• Skin examination for melanoma (including scalp and posterior auricular region)

Common Pitfalls to Avoid

• Do not rely on non-contrast CT as the primary modality—it will miss small metastases and most posterior fossa lesions 1, 4
• Do not assume normal neurological examination excludes significant pathology in the setting of progressive symptoms 6
• Do not misinterpret post-treatment changes: Pseudoprogression after chemoradiation and pseudoregression after anti-angiogenesis therapy can mimic tumour progression or response 5
• Do not overlook screening in high-risk asymptomatic patients—early detection of brain metastases impacts clinical decision-making and may improve outcomes 1
• Do not forget to assess for spinal involvement when leptomeningeal disease is suspected—complete spine imaging is essential 1, 2