6th August 2024

Space-occupying lesions

Overview of space-occupying lesions

Space-occupying lesions within the central nervous system can be diagnosed following presentation with either focal or generalised neurological features. The most common presenting feature is headache, although in 25% of patients, seizures are the initial presentation. Other classic findings include nausea and vomiting, sensory changes, aphasia, focal weakness, depressed level of consciousness, or cognitive and behavioural changes.

There are a number of possible aetiologies of space-occupying lesions, and these are broadly summarised below.

Primary and metastatic tumours

Brain tumours are the ninth most common neoplasm diagnosed in the UK and the second most common in children. The majority of primary brain tumours arise from the meninges and the most common of these by far are meningiomas, which are more common in women and likely to be benign.

Malignant brain tumours primarily arise from neuroepithelial tissue and are generally termed gliomas. The most common of these in adults is glioblastoma multiforme (GBM), a highly aggressive tumour of astrocyte origin. Their incidence is similar in men and women and is associated with advancing age. Less aggressive tumours (low-grade gliomas) are more common in children and young people and carry a better prognosis.

Other primary brain tumours include pituitary adenomas, haemangiomas, nerve sheath tumours, such as vestibular Schwannoma, and primary CNS lymphoma. When considering brain tumours, it is especially important to consider metastatic disease – metastatic deposits in the brain are significantly more common than primary brain tumours. Typical primary sites are: lung, breast, kidney, lower GI tract, and skin.

Investigation and management

Initial diagnosis is with contrast CT brain, though the preferred form of imaging is MRI with gadolinium contrast for better resolution and ability to identify tissue types. If metastatic disease is suspected, staging CT imaging should be arranged. If there are no concerns about raised intracranial pressure, and especially if there is concern of a CNS lymphoma (e.g. in the patient with HIV), a lumbar puncture should be performed for flow cytometry.

Management should be led by neurosurgical and oncology teams, but, in general, for lesions with mass effect and surrounding oedema, high-dose steroids should be given, unless there is a suspicion for CNS lymphoma. In this case, steroids should ideally be withheld until a tissue diagnosis is obtained. If the presentation was with seizures, anti-seizure medication should be started.

General principles for ongoing management are usually combination therapy – surgical resection, radiotherapy (including radiosurgery, e.g. Gamma Knife), and chemotherapy in select cases (temozolomide is standard for GBM).

Spinal cord lesions

These are relatively infrequently encountered compared to other CNS tumours but are an important cause of focal neurology, typically in conjunction with unremitting back pain. They are classified as intramedullary (within the substance of the cord), intradural but extramedullary (such as meningiomas or nerve sheath tumours), and extradural (usually metastases).

Like brain tumours, the majority of intramedullary spinal cord tumours are gliomas, with ependymomas predominating. Intradural but extramedullary lesions are most frequently meningiomas, but approximately a quarter are nerve sheath tumours – either Schwannomas or neurofibromas. Extradural lesions most frequently occur within the vertebral bodies and are most commonly caused by metastatic disease, typically from a breast, lung or prostate primary. They classically manifest with spinal cord or cauda equina compression but can cause intradural invasion.

Investigation of spinal cord lesions is primarily via MRI or CT myelogram for those unable to undergo MRI scanning. Management is usually a combination of surgery and radiotherapy.

Infectious and inflammatory causes

When considering an infectious or inflammatory cause of a space-occupying lesion, it is essential to ascertain any risks for immunosuppression, recent travel history, and the patient’s social context. Presentation is classically with headache and fever, potentially in combination with cranial nerve signs, meningeal irritation, seizures, or change in mental state or conscious level.

Inflammatory causes may present insidiously without a pre-existing diagnosis, for example in neurological manifestations of systemic lupus erythematosus. They may result in a range of symptoms, ranging from subtle focal neurology to seizures and coma.

Important things to establish when considering a patient with a potential infectious or inflammatory brain lesion:

• Is there underlying immune suppression? HIV, diabetes, and end-stage renal disease receiving haemodialysis are all risk factors for brain abscess formation, and it is important to consider opportunistic pathogens such as Toxoplasma gondii, the risk of which is increased by a low CD4 count (<100). Some medications, especially immunomodulatory agents, have been associated with PML.
• Has there been recent operative management of the brain or head and neck, including dental procedures?
• Is there a recent history of sinusitis, otitis or dental infection? The majority of brain abscesses form by direct spread, and there are characteristic organisms for different sites of origin:

• Has the patient recently travelled to an area where certain parasites are endemic? Taenia solium, for example, is known to be endemic in many regions of Central and South America and is the causative agent for neurocysticercosis.
• Are there risk factors for TB?
• Is there a history suggestive of an underlying systemic disorder? A careful systems review and examination is essential, especially if considering vasculitis or granulomatous disease, or MS-related lesions.

Initial investigation is via CT brain imaging with contrast, although once again MRI with gadolinium contrast provides best resolution; these may demonstrate ring-enhancing lesions. Lumbar puncture is frequently contraindicated, and it may be that direct biopsy is most diagnostic. It is also essential to perform blood cultures, and HIV serology may be helpful.

If there is suspicion of a brain abscess, broad-spectrum antibiotic therapy with good aerobic and anaerobic cover should be instituted urgently – this may include vancomycin, ceftriaxone, or metronidazole. Once a causative organism or underlying condition is identified, targeted therapy should be initiated, though neurosurgical intervention may be required. Steroids should be given if there is vasogenic oedema and mass effect, and prophylactic anticonvulsant therapy may be indicated.

References

• Cancer Research UK. Brain, other CNS and intracranial tumours statistics [Internet]. Cancer Research UK. 2021 [cited 11 Feb 2022]. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/brain-other-cns-and-intracranial-tumours/
• Hall W. Brain abscess. BMJ Best Practice [Internet]. 2021 [cited 11 Feb 2022]. Available from: https://bestpractice.bmj.com/topics/en-gb/925/
• Manji H, Connolly S, Kitchen N, Lambert C, Mehta A. Oxford Handbook of Neurology [Internet]. 2nd ed. Oxford: Oxford University Press; 2014 [cited 29 November 2021]. Available from: https://oxfordmedicine.com/view/10.1093/med/9780199601172.001.0001/med-9780199601172
• Southwick F. Pathogenesis, clinical manifestations, and diagnosis of brain abscess. UpToDate [Internet]. Eds: Tunkel A, Hall K. 2021 [cited 11 Feb 2022]. Available from: https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-brain-abscess
• Welch W, Schiff D, Gerszten P. Spinal cord tumours. UpToDate [Internet]. Eds: Loeffler J, Wen P, Eichler A. 2021. [cited 11 Feb 2022]. Available from: https://www.uptodate.com/contents/spinal-cord-tumors
• Wong E, Wu J. Overview of the clinical features and diagnosis of brain tumours in adults. UpToDate [Internet]. Eds: Eds: Loeffler J, Wen P, Eichler A. 2021. [cited 11 Feb 2022]. Available from: https://www.uptodate.com/contents/overview-of-the-clinical-features-and-diagnosis-of-brain-tumors-in-adults