Raised intracranial pressure, brain tumours and paraneoplastic neurological syndromes

Overview

The skull is a closed box. Any extra volume (tumour, abscess, blood, swelling or trapped CSF) eventually raises intracranial pressure (ICP), reduces brain perfusion and pushes brain tissue through openings in the dura and skull (herniation), which can kill. Brain tumours are a common cause of this, but they more often present with seizures or a progressive focal deficit. Paraneoplastic syndromes are the remote, non-metastatic neurological effects of cancer.

(Hydrocephalus, idiopathic intracranial hypertension and head injury are covered in their own chapters.)

Part 1: Raised intracranial pressure

Physiology: the Monro-Kellie doctrine

• The cranium holds brain, blood and CSF; their total volume stays constant.
• A growing mass is first compensated by pushing out CSF (into the spinal sac) and venous blood. Pressure barely rises.
• When compensation is used up, a small further rise in volume causes a steep rise in pressure (decompensation).
• Normal CSF pressure at LP is about 60–150 mm of CSF.

Cerebral perfusion pressure (CPP) = mean arterial pressure (MAP) − ICP. A sustained ICP above about 20–25 mmHg carries a poor outcome, and a CPP of at least 60 mmHg is targeted in severe brain injury.

Causes

Clinical features

Early:

• Headache: generalised, worse on waking and lying flat, worse on coughing, straining or bending; may improve after getting up.
• Vomiting, often in the morning, sometimes without nausea.
• Papilloedema: swollen optic discs with blurred margins, loss of spontaneous venous pulsation, haemorrhages; vision is usually normal at first apart from an enlarged blind spot and brief visual obscurations on bending or coughing.

False localising signs (they do not point to the site of the mass):

Late (herniation, "coning"):

• Falling consciousness (the most important sign; monitor with the Glasgow Coma Scale).
• Cushing triad: hypertension (widening pulse pressure), bradycardia, irregular breathing.
• Decerebrate posturing, bilateral fixed pupils, apnoea and death.

Investigations

• Urgent CT (shows mass, bleed, hydrocephalus, oedema, midline shift, effaced sulci and basal cisterns).
• MRI with contrast for tumours, posterior fossa lesions and abscess; MR or CT venography for venous sinus thrombosis.
• ICP monitoring (intraparenchymal bolt or external ventricular drain) in intensive care.

Management

General measures:

• ABC; intubate if GCS is low or the airway is threatened.
• Head of the bed raised, head in the midline, avoid tight collars or ties around the neck (improve venous drainage).
• Treat fever, seizures, pain and agitation (sedation); avoid hypoxia, hypotension and hypercapnia.
• Avoid hypotonic fluids; keep sodium normal or slightly high.

Specific measures:

Part 2: Brain tumours

Epidemiology

• Primary intracranial tumours are about 3% of all cancers.
• In adults, metastases are commoner than primary tumours (about half of all brain tumours).
• Metastases come mainly from lung (bronchus), breast, melanoma, kidney and gastrointestinal cancers; they are often multiple and at the grey-white junction.
• Primary tumours rarely spread outside the CNS.

Main tumour types

Clinical features

Brain tumours cause symptoms in three ways:

1. Local (direct) effects: progressive focal deficit, depending on site:
   • Frontal: personality change, apathy, disinhibition, expressive aphasia (dominant), anosmia; Foster Kennedy syndrome (olfactory groove meningioma: same-side optic atrophy, opposite-side papilloedema, anosmia).
   • Temporal: memory and language problems, upper quadrant field defect, complex partial seizures.
   • Parietal: sensory loss, neglect, lower quadrant field defect, dyspraxia.
   • Occipital: homonymous hemianopia.
   • Cerebellum and brainstem: ataxia, nystagmus, cranial nerve palsies, early hydrocephalus.
2. Raised ICP (above), often from obstructive hydrocephalus with posterior fossa tumours, or late with hemisphere tumours.
3. Seizures: focal seizures, with or without spread to tonic-clonic, are a common first feature of hemisphere tumours, especially slow-growing ones. A first seizure in an adult needs brain imaging.

The tempo matters: weeks in glioblastoma, years in meningioma.

Investigations

• MRI with contrast is the best test (superior for the posterior fossa); CT is the first scan in emergencies.
• Search for a primary when metastasis is possible: chest X-ray, CT chest, abdomen and pelvis, breast examination, skin check (melanoma).
• Stereotactic biopsy or resection for histology and molecular markers.
• LP is contraindicated with a mass lesion.
• Differentials of a ring-enhancing mass: abscess (restricted diffusion), tuberculoma, toxoplasmosis, cysticercosis, lymphoma, resolving haematoma.

Management

• Dexamethasone (with a proton pump inhibitor cover) for vasogenic oedema: rapid improvement in headache and deficits.
• Anticonvulsants for seizures (e.g. levetiracetam).
• Surgery:
  • Gliomas: maximal safe resection (they infiltrate, so recurrence is usual), then radiotherapy plus temozolomide (oral alkylating agent) for glioblastoma.
  • Meningioma: surgical excision is often curative; small, symptom-less ones in the elderly can be watched; radiosurgery for inaccessible tumours.
  • Vestibular schwannoma: observation, microsurgery or stereotactic radiosurgery.
  • Medulloblastoma: surgery, craniospinal radiotherapy and chemotherapy.
• Metastases: steroids; surgery or stereotactic radiosurgery for a single or few accessible lesions; whole-brain radiotherapy for many; treat the primary.
• Primary CNS lymphoma: high-dose methotrexate-based chemotherapy (not surgery); restore immunity in HIV.
• Palliative and rehabilitation support; driving restrictions after seizures.

Part 3: Paraneoplastic neurological syndromes

What they are

• Neurological disorders caused by cancer without direct invasion or metastasis.
• Autoimmune: the tumour expresses neuronal proteins; antibodies (and T cells) then attack the nervous system.
• The neurological syndrome usually appears before the cancer is diagnosed, often by months.
• Commonest associated tumours: small-cell lung cancer, breast, ovarian (including teratoma), testicular, thymoma and Hodgkin lymphoma.
• Neuroimaging is often normal; diagnosis rests on the clinical pattern and antibody testing, then a search for the cancer (CT chest, abdomen, pelvis, PET, mammography, pelvic ultrasound, testicular ultrasound).

Syndromes, antibodies and tumours

Management

• Find and treat the tumour: this offers the best chance of stabilising the neurological disease.
• Immunotherapy: steroids, IVIG, plasma exchange, rituximab or cyclophosphamide.
• Syndromes caused by antibodies against surface receptors (NMDA, VGCC in LEMS) respond well; those with intracellular antigen antibodies (Hu, Yo) usually respond poorly because neurones are destroyed by T cells.
• LEMS also responds to 3,4-diaminopyridine (amifampridine); removal of the ovarian teratoma often cures anti-NMDA encephalitis.

Quick revision

• Monro-Kellie: compensation by CSF and venous blood, then a steep pressure rise.
• Raised ICP: headache on waking and coughing, vomiting, papilloedema; late falling GCS, Cushing triad.
• False localising: VI nerve palsy; uncal herniation gives a same-side fixed dilated pupil.
• CPP = MAP − ICP; aim for at least 60 mmHg; ICP above 20–25 mmHg is dangerous.
• Treat: head up, osmotic therapy (mannitol, hypertonic saline), dexamethasone for tumour oedema, brief hyperventilation, surgery or CSF drainage; no LP.
• Adults: metastases (lung, breast, melanoma, kidney, bowel), glioblastoma, meningioma; children: posterior fossa (medulloblastoma, pilocytic astrocytoma, ependymoma).
• Glioblastoma: ring enhancement, necrosis, crosses corpus callosum; resection, radiotherapy, temozolomide.
• Paraneoplastic: anti-Hu (SCLC), anti-Yo (ovary/breast), anti-Ri (opsoclonus), anti-NMDA (teratoma), VGCC (LEMS); usually precede the cancer.

Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Bailey and Love's Short Practice of Surgery).

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